Cjc 1295 half life

Cjc 1295 half life DEFAULT

Prolonged Stimulation of Growth Hormone (GH) and Insulin-Like Growth Factor I Secretion by CJC, a Long-Acting Analog of GH-Releasing Hormone, in Healthy Adults

Abstract

Context: Therapeutic use of GHRH to enhance GH secretion is limited by its short duration of action.

Objective: The objective of this study was to examine the pharmacokinetic profile, pharmacodynamic effects, and safety of CJC, a long-acting GHRH analog.

Design: The study design was two randomized, placebo-controlled, double-blind, ascending dose trials with durations of 28 and 49 d.

Setting: The study was performed at two investigational sites.

Participants: Healthy subjects, ages 21–61 yr, were studied.

Interventions: CJC or placebo was administered sc in one of four ascending single doses in the first study and in two or three weekly or biweekly doses in the second study.

Main Outcome Measures: The main outcome measures were peak concentrations and area under the curve of GH and IGF-I; standard pharmacokinetic parameters were used for CJC

Results: After a single injection of CJC, there were dose-dependent increases in mean plasma GH concentrations by 2- to fold for 6 d or more and in mean plasma IGF-I concentrations by to 3-fold for 9–11 d. The estimated half-life of CJC was – d. After multiple CJC doses, mean IGF-I levels remained above baseline for up to 28 d. No serious adverse reactions were reported.

Conclusions: Subcutaneous administration of CJC resulted in sustained, dose-dependent increases in GH and IGF-I levels in healthy adults and was safe and relatively well tolerated, particularly at doses of 30 or 60 μg/kg. There was evidence of a cumulative effect after multiple doses. These data support the potential utility of CJC as a therapeutic agent.

THE USE OF GH for the treatment of children with impaired linear growth has been accepted as an important therapeutic modality for more than 50 yr (1). An unlimited supply of the hormone, made possible by the availability of recombinant GH in the s, permitted expansion of the target population to include GH-deficient adults. Most adults receiving GH today have primary pituitary disease with impaired GH secretory capacity. However, most children being treated with GH have no evidence of pituitary disease and are believed to have an impaired hypothalamic signaling mechanism due to a GHRH neurosecretory dysfunction. GH has also been used for therapy of disorders in children and adults in which pituitary function is either intact or only slightly impaired, such as chronic renal failure and Turner syndrome (in children) and HIV-related wasting and lipodystrophy and burn therapy (in adults).

In patients with intact pituitary function, there has been interest in the use of GHRH rather than GH in the hope of producing a more physiological pattern of tissue exposure to GH than occurs by a single daily injection of the hormone. In fact, several studies in both children and adults have suggested that comparable or near-comparable results can be achieved with GHRH therapy (2–4).

A major limitation in the use of GHRH for therapy, however, is its short half-life. Native GHRH, a amino acid peptide, has a half-life of 7 min (5), which is even shorter than that of GH (12 min) (6), necessitating daily or even more frequent injections. Polyethylene glycol-conjugated GHRH has been studied in an effort to overcome this limitation (7).

A synthetically modified form of GHRH has been linked to a reactive chemical that enables binding to endogenous serum albumin after sc administration. The chemical structure of this compound, drug affinity complex-GH-releasing factor (DAC-GRF; CJC, ConjuChem, Inc., Montréal, Canada) is shown in Fig. 1. The core therapeutic moiety is GHRH-(1–29)NH2, which contains the full biological activity of GHRH-(1–44)NH2 modified by substitution of four amino acids that serve to render the compound more resistant to proteolytic cleavage (herein called GRF). GRF is linked by the amino acid, lysine, to a reactive chemical [maleimidoproprionic acid (MPA)] that binds to unpaired thiol (sulfhydryl) groups. The predominant free thiol group available for binding after parenteral administration is the single unpaired cysteine (cysteine 34) in serum albumin. At least 90% of CJC binds covalently to albumin in this fashion, with trace amounts found bound to fibrinogen and IgG. No other chemical species have been found bound to DAC-GRF after administration (data on file, ConjuChem, Inc.). This binding extends the half-life of the active pharmacophore, resulting in a markedly prolonged duration of action in several animal species (8). Moreover, studies in both dogs and pigs indicate that physiological GH secretion is maintained, and IGF-I levels are enhanced for several days after a single administration.

We assessed the safety, tolerability, pharmacokinetic profile, and effect of CJC on circulating concentrations of GH and IGF-I in two randomized, placebo-controlled, double-blind, dose-escalating studies in healthy adult subjects.

Fig. 1.

Chemical structure of the CJC (DAC-GRF). The core therapeutic moiety is a tetrasubstituted GHRH-(1–29)NH2. The substituted amino acids are shown in italics. The linker is lysine, and the reactive chemical is maleimidoproprionic acid that binds covalently to the single unpaired cysteine (cysteine 34) in serum albumin.

Fig. 1.

Chemical structure of the CJC (DAC-GRF). The core therapeutic moiety is a tetrasubstituted GHRH-(1–29)NH2. The substituted amino acids are shown in italics. The linker is lysine, and the reactive chemical is maleimidoproprionic acid that binds covalently to the single unpaired cysteine (cysteine 34) in serum albumin.

Subjects and Methods

The subjects consisted of healthy men and women, ages 21–61 yr, with a body mass index of 30 kg/m2 or less and IGF-I levels in the normal range for age and gender. Appropriately constituted independent ethics committees reviewed and approved each of the studies, and written informed consent of all subjects was obtained before participation.

Study design

Study 1 was an ascending, randomized, double-blind, placebo-controlled single-dose trial performed at SFBC International, Inc. (Miami, FL). Study 2 was an ascending, randomized, double-blind, placebo-controlled multiple-dose trial performed at Kendle International BV (Utrecht, The Netherlands).

In study 1, four sequential, dose-escalation groups were evaluated. These dose levels were 30 μg/kg (n = 6, five active and one placebo), 60 μg/kg (n = 6, five active and one placebo), μg/kg (n = 6, five active and one placebo), and μg/kg (n = 6, five active and one placebo). An additional cohort of 18 subjects (15 active and three placebo) subsequently received μg/kg.

Serum GH was measured on d 0 at 60, 30, and 15 min before study drug dosing; at 15, 30, and 60 min and 2, 3, 4, 6, 8, 10, 12, and 24 h after dosing; and then every 8 h on d 2–3, then daily on d 4, 5, 6, 7, 9, 11, 14, 21, and Serum IGF-I and CJC were measured on d 0, 1, 2, 3, 4, 5, 6, 7, 9, 11, 14, 21, and

In study 2, 24 subjects were enrolled in one of four sequential dosing cohorts. Group 1 (n = 6, five active and one placebo) received two injections of 30 μg/kg (d 0 and 14), group 2 (n = 6, five active and one placebo) received two injections of 60 μg/kg (d 0 and 14), group 3 (n = 6, five active and one placebo) received three injections of 30 μg/kg (d 0, 7, and 14), and group 4 (n = 6, five active and one placebo) received three injections of 20 μg/kg (d 0, 7, and 14). Sample collection was similar to that in study 1, with the addition of more frequent pre- and postinjection sampling on d 7 (groups 3 and 4 only) and 14 as well as a final sample collection on d 49 in all subjects.

Serial clinical evaluations (vital signs, adverse events, and physical examination) and laboratory safety assessments (serum chemistry, hematology, and urinalysis) were performed ending on d 28 in study 1 and on d 49 in study 2.

Laboratory methods

GH.

Serum GH was measured by a double antibody RIA (Esoterix Laboratory Services, Inc., Calabasas Hills, CA). The assay sensitivity was ng/ml, and the coefficient of variation was 10%.

IGF-I.

Serum IGF-I was measured by a double antibody RIA by Esoterix Laboratory Services, Inc., after ethanol extraction and with the addition of IGF-2 as a blocking agent. The assay sensitivity was 10 ng/ml, and the coefficient of variation was %. Normal ranges for the assay are age and gender adjusted.

Other hormones.

Serum cortisol, prolactin, TSH, and LH concentrations were measured in patients receiving 60 μg/kg CJC in study 1 by Esoterix Laboratory Services, Inc.

CJC

Plasma CJC concentrations were measured by RIA at PPD Development, LP (Richmond, VA), using a rabbit anti-(tetra-substituted)GRF-(1–29) coupled to keyhole limpet hemocyanin and radioiodinated GRF-(1–29). The antibody exhibited % cross-reactivity with albumin-bound DAC of the tetrasubstituted GRF-(1–29). There was no cross-reactivity with native GRF-(1–29), native GRF-(3–29), or the DAC of the fragment 12–29 of the tetrasubstituted GRF. There was 25% cross-reactivity with free (nonalbumin-bound) tetrasubstituted GRF-(1–29). The lower limit of detection was nmol/liter, and the mean intra- and interassay coefficients of variation were % and %, respectively.

Pharmacokinetic analysis.

Pharmacokinetic parameters [peak plasma concentrations (Cmax), time to peak plasma concentrations (Tmax), and area under the curve (AUC)] of CJC, GH, and IGF-I were calculated from the concentration vs. time values for each patient using a compartment model in the single-dose study (WinNonlin Professional version , Pharsight Corp., Mountain View CA) and a noncompartmental model in the multiple-dose study (WinNonlin Professional version ).

Antibody formation.

A validated immunoradiometric assay was used to determine the presence of antibodies to CJC The anti-CJC antibody was raised in rabbits by immunization with a CJC analog [the tetrasubstituted GRF-(1–29)] to which a cysteine residue was added at position 30 to permit direct conjugation to keyhole limpet hemocyanin to make the molecule more immunogenic. This antibody was also used in the assay for plasma CJC concentrations. In this immunoradiometric assay, tubes are coated with CJC bound to inactivated MPA. Test samples or affinity-purified rabbit anti-CJC antibody controls in human serum were added. After incubation, tubes were washed and [I]protein LA (Sigma-Aldrich, St. Louis, MO) was added. After incubation, tubes were washed again, radioactivity was determined in a γ-counter, and the specific binding of the samples was calculated.

Statistical analysis

Mean and variance estimates were calculated for all pharmacokinetic parameters by dose group. Cmax and AUC to the last sampling time (AUCt) were log transformed before analysis, and AUC values were calculated using the linear trapezoidal rule. Differences in GH and IGF-I levels and AUC between groups were compared by ANOVA and/or one-tailed t test; P < was considered significant. All statistical analyses were performed using SAS version (SAS Institute, Cary, NC).

Because all enrolled subjects received at least one dose of the study drug, all available data are included in analyses of safety, pharmacokinetic, and pharmacodynamic parameters. No effort to estimate missing data was made, with the exception of AUC calculations.

Subjects receiving placebo in all dosing groups in each study were pooled for comparison with groups treated with active drug.

Results

Subject characteristics and disposition

The distribution of subjects in the study groups by age and gender is shown in Table 1. The mean overall age of subjects in the two studies was ± (±se) yr (range, 21–61 yr), and 44% of subjects were men. Although the dosing cohort groups in both studies were generally similar in mean age, gender, height, weight, and BMI, subjects in group 2 in study 2 were younger (mean age, 33 yr), and 80% were men. Two subjects in study 1 (both randomized to the μg/kg dosing cohort) and one subject in study 2 (in group 2) discontinued the study prematurely. The subjects in study 1 withdrew 5 and 22 d after dosing because of mild injection site reactions. The subject in study 2 withdrew 6 d after experiencing multiple mild adverse effects following a single injection of 30 μg/kg.

TABLE 1.

Study drug doses and regimens with subject information

Total no. . Age ± sd . No. of men . No. of women . No. of doses . Dosing days . 
Study 1 
    Dose 
        30 μg/kg 55 ± 8 
        60 μg/kg 53 ± 7 
         μg/kg 20 50 ± 6 13 
         μg/kg 53 ± 3 
    Pooled placebo 52 ± 7 
Study 2 
    Dose 
        20 μg/kg 43 ± 14 d 0, 7, 14 
        30 μg/kg 33 ± 15 d 0, 7, 14 
        30 μg/kg 40 ± 11 d 0, 14 
        60 μg/kg 57 ± 1 d 0, 14 
    Pooled placebo 51 ± 13 2 or 3 d 0, 14, or d 0, 7, 14 
Total no. . Age ± sd . No. of men . No. of women . No. of doses . Dosing days . 
Study 1 
    Dose 
        30 μg/kg 55 ± 8 
        60 μg/kg 53 ± 7 
         μg/kg 20 50 ± 6 13 
         μg/kg 53 ± 3 
    Pooled placebo 52 ± 7 
Study 2 
    Dose 
        20 μg/kg 43 ± 14 d 0, 7, 14 
        30 μg/kg 33 ± 15 d 0, 7, 14 
        30 μg/kg 40 ± 11 d 0, 14 
        60 μg/kg 57 ± 1 d 0, 14 
    Pooled placebo 51 ± 13 2 or 3 d 0, 14, or d 0, 7, 14 

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TABLE 1.

Study drug doses and regimens with subject information

Total no. . Age ± sd . No. of men . No. of women . No. of doses . Dosing days . 
Study 1 
    Dose 
        30 μg/kg 55 ± 8 
        60 μg/kg 53 ± 7 
         μg/kg 20 50 ± 6 13 
         μg/kg 53 ± 3 
    Pooled placebo 52 ± 7 
Study 2 
    Dose 
        20 μg/kg 43 ± 14 d 0, 7, 14 
        30 μg/kg 33 ± 15 d 0, 7, 14 
        30 μg/kg 40 ± 11 d 0, 14 
        60 μg/kg 57 ± 1 d 0, 14 
    Pooled placebo 51 ± 13 2 or 3 d 0, 14, or d 0, 7, 14 
Total no. . Age ± sd . No. of men . No. of women . No. of doses . Dosing days . 
Study 1 
    Dose 
        30 μg/kg 55 ± 8 
        60 μg/kg 53 ± 7 
         μg/kg 20 50 ± 6 13 
         μg/kg 53 ± 3 
    Pooled placebo 52 ± 7 
Study 2 
    Dose 
        20 μg/kg 43 ± 14 d 0, 7, 14 
        30 μg/kg 33 ± 15 d 0, 7, 14 
        30 μg/kg 40 ± 11 d 0, 14 
        60 μg/kg 57 ± 1 d 0, 14 
    Pooled placebo 51 ± 13 2 or 3 d 0, 14, or d 0, 7, 14 

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Plasma CJC concentrations

In study 1, the mean Cmax of CJC increased with dose, with values of , , , and nmol/liter in the 30, 60, , and μg/kg single-dose groups, respectively (Fig. 2). Maximum drug concentrations were reached between 1 and h in all groups. The mean AUCt in the 30, 60, , and μg/kg dose groups were , , , and h·nmol/liter, respectively, with dose-proportionality observed in the 60, , and μg/kg dose groups. Terminal elimination rate, systemic clearance, and volume of distribution gradually increased with dose. The mean half-life ranged from – d; mean systemic clearances were , , , and liters/h/kg, and mean volumes of distribution were , , , and liter/kg in the four dose groups, respectively.

Fig. 2.

Plasma disappearance curves of CJC after a single sc injection. Shown are the mean ± sd half-life. Drug concentrations were generally measurable for at least 12–14 d after injection.

Fig. 2.

Plasma disappearance curves of CJC after a single sc injection. Shown are the mean ± sd half-life. Drug concentrations were generally measurable for at least 12–14 d after injection.

In study 2, maximum CJC plasma concentrations were 11–32% higher after the injection on d 7 than on d 0 in the two groups that received weekly injections (data not shown). After the d 14 injection, maximum CJC concentrations were 29–70% higher than those on d 0 in all four groups. Similar increases occurred in AUC0–24 h on d 7 (12% and 15%) in groups 3 and 4 and in all four dosing groups on d 14 (31–57%). The 0–24 h AUC values were dose dependent.

Maximum drug concentrations were typically reached within – h after injection, but there was a high degree of individual variability. The variability increased with subsequent doses, but did not appear to be dose dependent. Drug concentrations were measurable for 10–14 d. In subjects in whom samples were obtained for up to 14 d, the mean estimated half-life of CJC ranged from – d, and the mean clearance was between and liters/h. The pharmacokinetic parameters were independent of body weight.

Serum GH concentrations

In study 1, mean preinjection GH concentrations ranged from – ng/ml. Mean GH concentrations increased by 2- to fold after single-dose injection of CJC through d 6 (Fig. 3A). In contrast, mean GH concentrations remained stable in the placebo group. The mean GH AUC0–7 d values were elevated in a dose-dependent manner, although only the groups receiving 60, , and μg/kg had significant increases compared with the placebo group (Fig. 3B).

Fig. 3.

GH responses to a single sc injection of CJC A, Serum GH concentrations (mean ± sd) are shown and suggest that pulsatile hormone secretion is maintained. B, Mean GH AUC0–7 d, expressed as a percent increase over placebo. *, P < vs. placebo. Shown are the mean ± sd. Mean maximum concentrations of GH were , , , and ng/ml in the 30, 60, , and μg/kg groups; mean AUC were , , , and ng/ml·h, respectively.

Fig. 3.

GH responses to a single sc injection of CJC A, Serum GH concentrations (mean ± sd) are shown and suggest that pulsatile hormone secretion is maintained. B, Mean GH AUC0–7 d, expressed as a percent increase over placebo. *, P < vs. placebo. Shown are the mean ± sd. Mean maximum concentrations of GH were , , , and ng/ml in the 30, 60, , and μg/kg groups; mean AUC were , , , and ng/ml·h, respectively.

The median peak GH level occurred within 1 h in all dosing groups in both studies, with the exception of the group receiving a single μg/kg dose of CJC, in which the median peak GH level occurred at 4 h. The mean peak GH levels were more variable and occurred –4 h after dosing. The variability was neither dose dependent nor progressive.

Serum IGF-I concentrations

Mean preinjection IGF-I concentrations ranged from – ng/ml in study 1. IGF-I levels remained elevated compared with baseline for 9–11 d after a single injection of CJC in all dosing groups in study 1, and mean levels increased by to 3-fold over baseline (Fig. 4A). Mean IGF-I AUC0–7 d values were elevated in a dose-dependent manner, reaching statistical significance compared with baseline in the groups receiving 60, , and μg/kg (Fig. 4B). IGF-I levels exceeded the age- and gender-adjusted normal ranges only in subjects receiving μg/kg CJC In contrast, mean IGF-I levels in the placebo group remained relatively stable during the same period. The time to peak IGF-I levels was dose dependent, occurring 2–3 d after administration of the lowest three doses, but not until 4 d after the highest dose. IGF-I levels remained at a plateau for up to 7 d, after which they gradually declined toward baseline. IGF-I levels remained elevated for at least 2 wk after injection in patients receiving the two highest doses.

Fig. 4.

IGF-I responses to a single sc injection of CJC A, Serum IGF-I concentrations (mean ± sd) are shown. B, Mean IGF-I AUC0–7 d, expressed as a percent increase over placebo. *, P < vs. placebo. Shown are the mean ± sd. The shaded area marked is the upper limit of normal (U.L.N.) for age- and gender-matched cohorts. Mean maximum concentrations of IGF-I were , , , and ng/ml in the 30, 60, , and μg/kg groups; mean AUC were 91, , , and μg/ml·h, respectively.

Fig. 4.

IGF-I responses to a single sc injection of CJC A, Serum IGF-I concentrations (mean ± sd) are shown. B, Mean IGF-I AUC0–7 d, expressed as a percent increase over placebo. *, P < vs. placebo. Shown are the mean ± sd. The shaded area marked is the upper limit of normal (U.L.N.) for age- and gender-matched cohorts. Mean maximum concentrations of IGF-I were , , , and ng/ml in the 30, 60, , and μg/kg groups; mean AUC were 91, , , and μg/ml·h, respectively.

In study 2, mean IGF-I levels increased within 8 h of CJC injection and remained above baseline levels through d 28 (Fig. 5). Mean IGF-I values remained elevated above baseline before the second and/or third doses in all CJCtreated groups, although this reached significance only for group 4 (P < for group 4 and P < for group 3, by paired t test). Maximum IGF-I levels after the second and/or third injections were progressively greater than after the initial injection (data not shown). In addition, the Tmax for IGF-I was progressively shorter after subsequent injections (data not shown).

Fig. 5.

IGF-I responses to multiple sc injections of CJC Serum IGF-I concentrations (mean ± se) are shown. Arrows indicate days of injection. A, Changes in serum IGF-I levels after three weekly injections of CJC or placebo. B, Changes in serum IGF-I levels after two biweekly injections of CJC or placebo. In both A and B, for d 0–7 and 14–21, the entire pooled placebo group (n = 4) is plotted, because all these subjects received placebo injections on d 0 and In A, for the period from d 7–14, only the two subjects who received placebo injections on d 7 are plotted (i.e. three weekly injections). In B, for the period from d 7–14, only the two subjects who received placebo injections on d 0 and 14 are plotted (i.e. two biweekly injections).

Fig. 5.

IGF-I responses to multiple sc injections of CJC Serum IGF-I concentrations (mean ± se) are shown. Arrows indicate days of injection. A, Changes in serum IGF-I levels after three weekly injections of CJC or placebo. B, Changes in serum IGF-I levels after two biweekly injections of CJC or placebo. In both A and B, for d 0–7 and 14–21, the entire pooled placebo group (n = 4) is plotted, because all these subjects received placebo injections on d 0 and In A, for the period from d 7–14, only the two subjects who received placebo injections on d 7 are plotted (i.e. three weekly injections). In B, for the period from d 7–14, only the two subjects who received placebo injections on d 0 and 14 are plotted (i.e. two biweekly injections).

Mean AUC0–7 d and AUC0–14 d for IGF-I were significantly increased in group 2 (60 μg/kg) compared with group 1 (30 μg/kg; P = and P = , respectively) and were significantly greater in both groups compared with the placebo group (P = and P = , respectively). Mean AUC0–7 d, AUC7–14 d, and AUC14–21 d were all significantly higher in group 3 (30 μg/kg) than in group 4 (20 μg/kg; P = , P = , and P = , respectively).

Other than age, no significant predictors of IGF-I or GH response, including gender, baseline weight or body mass index, and lipid or glucose levels, were observed.

Other hormonal effects

There were no significant increases in serum cortisol, prolactin, TSH, or LH levels after a single injection of CJC (60 μg/kg), thus confirming the specificity of CJC for GH secretion (data not shown).

Safety

In the single-dose study, adverse events were reported in 33 (94%) vs. two (29%) subjects in the active and placebo groups, respectively; all were of mild to moderate severity, and none required medical intervention to resolve. Injection site reactions (irritation, erythema, induration, pain, or itching) occurred transiently (up to several hours) in approximately 70% of subjects receiving CJC and rarely in subjects receiving placebo. Injection site reactions tended to be more severe and/or prolonged after higher doses, with residual induration lasting up to 5 d. No local reaction exceeded 10 cm in diameter, and all resolved spontaneously. Transient urticarial rashes at the injection site occurred in almost 30% of subjects and were not dose related. Other adverse events reported in actively treated subjects included headache (63%), diarrhea (43%), and systemic vasodilatory reactions (flushing, warmth, and transient hypotension; 30%); all were more common at higher doses ( or μg/kg). Headache and diarrhea occurred occasionally at various times during the 7 d after dosing. Of these adverse events, only headache occurred in the placebo-treated group (14%). Overall, the adverse events observed at μg/kg were moderate in severity and resolved spontaneously after a few hours, whereas the μg/kg dose of CJC was considered well tolerated.

Injection site reactions (irritation, erythema, induration, pain, or itching) were reported in all actively treated subjects in study 2; all were mild in severity. Reactions were up to 10 cm in diameter. Mild injection site erythema (<2–3 cm) was reported in three of four placebo-treated subjects (75%) as well as induration and urticaria (<1–2 cm; 25%). Flushing occurred only in actively treated subjects, occurred within 30 min of injection, and resolved within 1–2 h. The incidence of flushing was dose dependent, with an incidence of 40% after low-dose and % after high-dose injections.

Other adverse events included transient loose stools/diarrhea (45% and % incidence in the and μg/kg groups, respectively), headache (non-dose dependent and ranging from 20–80% depending on the dose group), and nausea or abdominal pain (20%). Of these adverse events, only headache occurred in the placebo-treated group (14% in study 1 and 50% in study 2).

The incidence and severity of all adverse events were gender independent. There were no consistent changes in blood or urine laboratory values, including glucose levels and liver function studies, or in electrocardiographic findings in either study. No significant antibody formation was detected in subjects who received the active study drug.

A single subject in study 2 reported mild, transient (resolving fully and spontaneously in <24 h) involuntary leg muscle contractions and some loss of coordination after receiving the second biweekly injection of 30 μg/kg. Two subjects experienced transient dizziness and hypotension after the first injection of 30 μg/kg that resolved spontaneously and did not recur after subsequent injections of CJC

Discussion

This report describes the safety, pharmacokinetic profile, and pharmacodynamic effects of CJC, a synthetic analog of GHRH that permanently and covalently binds to serum albumin after administration. Results of the single-dose and multiple-dose studies demonstrate a prolonged half-life of CJC (∼6–8 d) after sc administration, with measurable drug concentrations for 10–13 d after single or multiple doses. In addition, there was clear evidence of a dose-responsive and sustained biological effect, with elevated GH and IGF-I serum concentrations persisting for at least 6 and 14 d, respectively, after single doses of CJC In the multiple-dose study, there was a cumulative effect after two or three injections of CJC administered weekly or biweekly, with elevated levels of both GH and IGF-I above baseline on d 14 in most subjects. CJC was safe and generally well tolerated, particularly at doses of 30 and 60 μg/kg.

Treatment with human GH typically consists of a single daily injection of the hormone, resulting in transient supraphysiological levels, followed by a decline to baseline. However, failure to mimic the physiological pulsatile nature of GH secretion may preclude optimal therapeutic effects and may contribute to some of the adverse effects that have been observed even in the presence of normal serum IGF-I levels. In contrast, injections or infusions of GHRH stimulate the pulsatile release of GH (9, 10), but the short plasma half-life (7 min) (5) renders GHRH impractical for therapeutic use. Therefore, the availability of a GHRH preparation with sustained effect has important therapeutic potential.

The half-life of CJC, as predicted from preclinical animal studies (8), was substantially prolonged compared with that of native GHRH, ranging from – d in the single-dose study and from – d in the multiple-dose study. Maximum concentrations were typically reached within 2 h after injection and exhibited a slow exponential decrease over several days. The disappearance rates were not dose dependent, although serum CJC concentrations were proportional to the dose injected. In the multiple-dose study, Cmax and AUC0–24 h were 17% greater on d 7 than on d 0 and from 30–70% greater on d 14 than on d 0.

Administration of single doses of CJC resulted in a 2- to fold increase in mean serum GH levels in all dosing groups, which was dose incremental and persisted for up to 6 d. Similarly, a dose-related increase in mean serum IGF-I levels was observed at all dose levels, ranging from to 3-fold and persisting for up to 14 d. Administration of ascending multiple doses of CJC resulted in elevated levels of GH, similar to those observed after a single dose.

In contrast, elevations in IGF-I levels showed a progressive effect over time, particularly in subjects receiving CJC every 7 d. Results of the multiple-dose study suggest both a cumulative pharmacokinetic effect [i.e. persistence of elevated predose levels of IGF-I in all dosing groups except group 1 (i.e. two injections of 30 μg/kg)] and a pituitary priming effect (i.e. progressively greater Cmax and progressively shorter Tmax after serial dosing). The data indicate that a minimum dosing interval of 7 d appears reasonable. The most appropriate dosing interval will be determined based on actual efficacy and safety data from longer-term therapeutic studies in patients with various clinical conditions.

No serious adverse reactions were reported in either study. The most frequently reported adverse events in subjects receiving CJC were injection site reactions, consisting of transient pain, swelling, and induration that were sometimes accompanied by local urticaria. Injection site reactions tended to be more severe and/or prolonged at higher dose levels. Headache, diarrhea, and flushing were also observed, with occasional transient and mild hypotension, but occurred primarily at higher doses.

Adverse effects complicate the use of GH in the treatment of HIV-associated metabolic conditions such as wasting and lipodystrophy. Although increases in the daily dose of GH from 1 to 6 mg are associated with dose-responsive benefits (11–13), doses of 2–3 mg/d or greater are associated with edema, arthralgias, and glucose intolerance. These side effects can become dose limiting. In the current studies, none of the subjects experienced these adverse effects. Future clinical trials on this disorder will confirm whether the use of GHRH rather than GH will circumvent these problems, as has been suggested in recent publications (4, 14).

In summary, a single sc administration of CJC produced sustained elevations of serum GH and IGF-I levels in normal subjects for nearly 2 wk. Weekly or biweekly administration of CJC resulted in stimulation of GH and IGF-I secretion for at least 7 d. Both single and multiple doses of CJC over 2 wk were safe and generally well tolerated, particularly at doses of 30 and 60 μg/kg. Future studies are indicated to evaluate the clinical utility of treatment with CJC in patients with intact GH secretory capacity.

Acknowledgments

This work was supported by ConjuChem, Inc. (Montréal, Canada).

Abbreviations:

  • AUC,

  • Cmax,

    peak plasma concentration;

  • DAC-GRF,

    drug affinity complex-GH-releasing factor;

  • MPA,

    maleimidoproprionic acid;

  • Tmax,

    time to peak plasma concentration.

References

2

Brain

C

,

Hindmarsh

PC

,

Pringle

PJ

,

Brook

CGD

Use of continuous subcutaneous growth hormone-releasing hormone (GHRH (1–29)NH2) infusions to augment growth hormone secretion and to promote growth.

Acta Paediatr Scand

78

:

3

Thorner

M

,

Rochiccioli

P

,

Colle

M

,

Lanes

R

,

Grunt

J

,

Galazka

A

,

Landy

H

,

Eengrand

P

,

Shah

S

Once daily subcutaneous growth hormone-releasing hormone therapy accelerates growth in growth hormone-deficient children during the first year of therapy. Geref International Study Group.

J Clin Endocrinol Metab

81

:

4

Koutkia

P

,

Canavan

B

,

Breu

J

,

Torriani

M

,

Kissko

J

,

Grinspoon

S

Growth hormone-releasing hormone in HIV-infected men with lipodystrophy: a randomized controlled trial.

JAMA

:

5

Frohman

LA

,

Downs

TR

,

Williams

TC

,

Heimer

EP

,

Pan

Y-CE

,

Felix

AM

Rapid enzymatic degradation of growth hormone-releasing hormone by plasma in vitro and in vivo to a biologically inactive, N-terminally cleaved product.

J Clin Invest

78

:

6

Bright

GM

,

Veldhuis

JD

,

Iranmanesh

A

,

Baumann

G

,

Maheshwari

H

,

Lima

J

Appraisal of growth hormone (GH) secretion: evaluation of a composite pharmacokinetic model that discriminates multiple components of GH input.

J Clin Endocrinol Metab

84

:

7

Munafo

A

,

Nguyen

TXQ

,

Papasouliotis

O

,

Lécuelle

H

,

Priestley

A

,

Thorner

MO

Polyethylene glycol-conugated growth hormone-releasing hormone is long-acting and stimulates GH in healthy young and elderly subjects.

Eur J Endocrinol

:

8

Benquet

C

,

Castaigne

J-P

,

Pham

K

,

Robitaille

M

,

Frohman

LA

, CJC (DAC-GRF), a long acting GRF analog, enhances pulsatile GH secretion, increases IGF-I levels, and restores linear growth. Program of the 86th Annual Meeting of The Endocrine Society,

New Orleans, LA

,

, p

9

Webb

CB

,

Vance

ML

,

Thorner

MO

,

Perisutti

G

,

Thominet

J

,

Rivier

J

,

Vale

W

,

Frohman

LA

Plasma growth hormone responses to constant infusions of human pancreatic growth hormone releasing factor: intermittent secretion or response attenuation.

J Clin Invest

74

:

96

10

Vance

ML

,

Kaiser

DL

,

Evans

WS

,

Furlanetto

R

,

Vale

W

,

Rivier

J

,

Thorner

MO

Pulsatile growth hormone secretion in normal man during a continuous hour infusion of human growth hormone releasing factor (l).

J Clin Invest

75

:

11

Andersen

O

,

Haugaard

SB

,

Flyvbjerg

A

,

Andersen

UB

,

Orskov

H

,

Madsbad

S

,

Nielsen

JO

,

Iversen

J

Low-dose growth hormone and human immunodeficiency virus-associated lipodystrophy syndrome: a pilot study.

Eur J Clin Invest

34

:

12

Engelson

ES

,

Glesby

MJ

,

Mendez

D

,

Albu

JB

,

Wang

J

,

Heymsfield

SB

,

Kotler

DP

Effect of recombinant human growth hormone in the treatment of visceral fat accumulation in HIV infection.

J Acquired Immune Defic Syndr

30

:

14

Falutz

J

,

Allas

S

,

Kotler

D

,

Thompson

M

,

Koutkia

P

,

Albu

J

,

Trottier

B

,

Routy

J-P

,

Cote

P

,

Abribat

T

,

Grinspoon

S

A placebo-controlled, dose-ranging study of a growth hormone releasing factor in HIV-infected patients with abdominal fat accumulation.

AIDS

19

:

Copyright © by The Endocrine Society

Sours: https://academic.oup.com/jcem/article/91/3//

Once-daily administration of CJC, a long-acting growth hormone-releasing hormone (GHRH) analog, normalizes growth in the GHRH knockout mouse

Although the majority of children with isolated growth hormone (GH) deficiency have a good growth response to GH-releasing hormone (GHRH), the use of this therapeutic agent is limited by its very short half-life. Indeed, we have shown that, in mice with GHRH gene ablation (GHRH knockout; GHRHKO), even twice-daily injections of a GHRH analog are unable to normalize growth. CJC is a synthetic GHRH analog that selectively and covalently binds to endogenous albumin after injection, thereby extending its half-life and duration of action. We report the effects of CJC administration in GHRHKO animals. Three groups of 1-wk-old GHRHKO mice were treated for 5 wk with 2 microg of CJC at intervals of 24, 48, and 72 h. Placebo-treated GHRHKO mice and mice heterozygous for the GHRHKO allele served as controls. GHRHKO animals receiving daily doses of CJC exhibited normal body weight and length. Mice treated every 48 and 72 h reached higher body weight and length than placebo-treated animals, without full growth normalization. Femur and tibia length remained normal in animals treated every 24 and 48 h. Relative lean mass and subcutaneous fat mass were normal in all treated groups. CJC caused an increase in total pituitary RNA and GH mRNA, suggesting that proliferation of somatotroph cells had occurred, as confirmed by immunohistochemistry images. These findings demonstrate that treatment with once-daily administration of CJC is able to maintain normal body composition and growth in GHRHKO mice. The same dose is less effective when administered every 48 or 72 h.

Sours: https://pubmed.ncbi.nlm.nih.gov//
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CJC is an incredibly effective growth hormone and works by causing another substance to be secreted. It stimulates the release of your own body’s growth hormone which. Research show that after the age of 30 the body’s growth hormone level drops quickly and approximately 15% every 10 years. CJC is able to increase growth hormone naturally by binding to receptors for growth hormone releasing hormone (GHRH) on your brain and more specifically the pituitary gland. By doing this it triggers the brain to release growth hormone that would have otherwise been lost with age. Research completed with healthy men and women between the ages of 21 and 61, showed that CJC had the ability to  increase serum growth hormone levels by %. In these individuals, the elevated growth hormone production and release continued for up to 6 days because CJC has a half life of about days. This longer half-life means the body continues to produces beyond the day of injection and is thought to be a great benefit has compared to other peptides that also have similar actions. For this reason and a few more, CJC has become very effective peptide for safely increasing growth hormone levels. 

CJC is safely biologically increased growth hormone levels without the side of effects of other medication such hGH treatment which have been none to have more side effects. Some of the side effects of CJC are generally mild and tend to not last long if at all such as headache, flushing, and dizziness. The most common reported side effect is redness and irritation at the injection site.

Sours: https://pramahtampa.com/services/performance/ipamorelin-cjc/

Modified GRF (CJC without DAC)

Modified Growth Releasing Factor aminos , usually referred to as Modified GRF () or “ModGRF(),” also known as CJC without DAC, is a synthetic analog of the endogenous peptide signaling hormone Growth Hormone Releasing Hormone (GHRH). Endogenously produced GHRH has 44 amino acids in its chain structure. A truncated synthetic form of GHRH called Sermorelin or GRF has 29 amino acids; Modified GRF () is further changed in that it has four substituted aminos in its chain that serve the purposes of preventing degradation and oxidation in manufacture and transport as well as in vivo, while also increasing binding affinity to the GHRH receptors.


Modified GRF () is not CJC nor should it be referred to as such. Modified GRF () is identical to the portion of CJC DAC that is not bound to MPA, minus the lysine. The presence of lysine in a literal “CJC without DAC” in the absence of MPA would have the opposite effect of DAC: it would drastically reduce the active life of the peptide to that of Sermorelin. Modified GRF () is the same as CJC without DAC.

Tetrasubstitued GRF ()

Modified GRF () is a synthetic modification of growth hormone releasing factor (GRF) with D-Ala, Gln, Ala, and Leu substitutions at positions 2, 8, 15, and 27 respectively. These substitutions create a much more stable peptide with the substitution at position 2 to prevent DPP-IV cleavage, position 8 to reduce asparagine rearrangement or amide hydrolysis to aspartic acid, position 15 to enhance bioactivity, and position 27 to prevent methionine oxidation.

CJC + DAC vs. CJC without DAC

CJC + DAC and CJC (also known as Modified GRF ) are both Growth Hormone Releasing Hormones (GHRH). Their action in the human body is identical but the difference between the two peptides are the span of the half-life. Modified GRF and Sermorelin have a very short acting half-life of about 30 minutes, while CJC + DAC has a half-life that can last up to approximately 8 days. Many a scientist have reported that the short half-life of Sermorelin and Modified GRF is considered to be much more natural as they produce a short pulse of Human Growth Hormone.

Purely for Scientific Research

Despite the fact that there has been plenty of research on Modified GRF in relation to how it functions and the benefits that can be derived from such functionality, it should be emphasized that the peptide is still just intended for scientific study at this point in time.  Because of this, any findings or observations relating to Modified GRF overall functionality, mechanics, benefits,  should exclusively be the product of study performed in a strictly contained environment.

Buy peptide

Sours: https://particlepeptides.com/en/content/cjcwithout-dac-

Half life 1295 cjc

Prolonged stimulation of growth hormone (GH) and insulin-like growth factor I secretion by CJC, a long-acting analog of GH-releasing hormone, in healthy adults

Context: Therapeutic use of GHRH to enhance GH secretion is limited by its short duration of action.

Objective: The objective of this study was to examine the pharmacokinetic profile, pharmacodynamic effects, and safety of CJC, a long-acting GHRH analog.

Design: The study design was two randomized, placebo-controlled, double-blind, ascending dose trials with durations of 28 and 49 d.

Setting: The study was performed at two investigational sites.

Participants: Healthy subjects, ages yr, were studied.

Interventions: CJC or placebo was administered sc in one of four ascending single doses in the first study and in two or three weekly or biweekly doses in the second study.

Main outcome measures: The main outcome measures were peak concentrations and area under the curve of GH and IGF-I; standard pharmacokinetic parameters were used for CJC

Results: After a single injection of CJC, there were dose-dependent increases in mean plasma GH concentrations by 2- to fold for 6 d or more and in mean plasma IGF-I concentrations by to 3-fold for d. The estimated half-life of CJC was d. After multiple CJC doses, mean IGF-I levels remained above baseline for up to 28 d. No serious adverse reactions were reported.

Conclusions: Subcutaneous administration of CJC resulted in sustained, dose-dependent increases in GH and IGF-I levels in healthy adults and was safe and relatively well tolerated, particularly at doses of 30 or 60 microg/kg. There was evidence of a cumulative effect after multiple doses. These data support the potential utility of CJC as a therapeutic agent.

Sours: https://pubmed.ncbi.nlm.nih.gov//
CJC 1295 Ipamorelin Mixing Instructions

CJC is a synthetic GHRH (growth hormone releasing hormone) analogue made up of 30 amino acids. It has been found to be highly effective with regards to the increase of growth hormone secretion and IGF-1 without negatively affecting the pulsatility of GH secretion.

CJC is often combined with Ipamorelin due to its enhanced specificity as a GHRH. This peptide generates similar increases in growth hormone secretion, but without the appetite stimulation and increase in cortisol, acetylcholine, prolactin, and aldosterone seen with other peptides in its class. This peptide has been found to be very well-tolerated and perfect when combined with Ipamorelin. 

Gland Stimulated: Pituitary

Benefits of CJC 

  • Increased growth hormone secretion and IGF-1 Levels with no increase in prolactin
  • Increased Body Weight and Length through increased protein synthesis
  • Increased Muscle Growth
  • Increased Bone Density
  • Improved Immune Function
  • Improved Cognition and Memory
  • Increased Collagen Production
  • Increased Fat Loss
  • Increased Cellular Repair and Regeneration

CJC also promotes slow wave deep sleep, which is responsible for the highest level of muscle growth and memory retention and rejuvenation.

Read our Guide to CJC  

Two types of CJC

GHRH (growth hormone releasing hormone) is produced in the hypothalamus. Its pulsatile release from the hypothalamus triggers a pulsatile release of GH from the pituitary gland. GHRH has a very short half-life of only a few minutes (half-life = the time required to remove half of the substance from the blood. The shorter the half-life, the more rapidly the substance is removed from the body, and the less its effect on the body).

The first 29 amino acids of GHRH is the active segment. They are available as a manufactured peptide called Sermorelin. Sermorelin was further modified to increase its half-life to 30 minutes. This is called CJC CJC was further modified by adding DAC (Drug Affinity Complex) to it. DAC binds to a blood protein called albumin, which increases it's half-life to 8 days. It is called CJC + DAC. CJC can also be compounded in a non-DAC form which mimics a more normal physiologic GH spike each night.

The longer half-life from the DAC binding to albumin means injections are only required once or twice per week. However, the long half-life and relatively constant blood level provide a constant stimulus for GH release from the pituitary through the GHRH receptor, which is not physiological. This can decrease the GH pulse amplitude which will result in decreased GH tissue stimulation.

Safety:

It is recommended when using a long-acting CJC molecule to have 'hormone holidays' of three months each three to six months, to allow the pituitary to 'recover'. During the holidays, Sermorelin is used instead of CJC + DAC.

The 'hormone holidays' may also minimize the risk of GH resistance developing. This resistance, or insensitivity, may occur via antibodies forming that bind to and inactivate GH, or by a decreased number of GH receptors on tissues (down-regulation). These are theoretical concerns as no long-term studies have been undertaken to clarify the issues.

Side effects of CJC may include injection site reactions (irritation, erythema, induration, pain, itching), headache, diarrhea, vasodilation (flushing, warmth, transient hypotension), nausea, abdominal pain.

Research:

Teichman SL, Neale A, Lawrence B, Gagnon C, Castaigne JP, Frohman LA. Prolonged stimulation of growth hormone (GH) and insulin-like growth factor I secretion by CJC, a long-acting analog of GH-releasing hormone, in healthy adults. J Clin Endocrinol Metab.  Mar;91(3) Epub Dec

Sackmann-Sala L, Ding J, Frohman LA, Kopchick JJ. Activation of the GH/IGF-1 axis by CJC, a long-acting GHRH analog, results in serum protein profile changes in normal adult subjects. Growth Horm IGF Res.  Dec;19(6) doi: /j.ghir Epub Apr

Merriam GR1, Buchner DM, Prinz PN, Schwartz RS, Vitiello MV. Potential applications of GH secretagogs in the evaluation and treatment of the age-related decline in growth hormone secretion. Endocrine.  Aug;7(1)

Sanders JL, Guo W, O'Meara ES, Kaplan RC, Pollak MN, Bartz TM, Newman AB, Fried LP, Cappola AR. Trajectories of IGF-I Predict Mortality in Older Adults: The Cardiovascular Health Study. J Gerontol A Biol Sci Med Sci. Jun 14;73(7)

Li Z1, Li Y2. Effect of growth hormone releasing hormone on chondrocytes of osteoarthritis. Korean J Intern Med.  Dec doi: /kjim

Barabutis N, Schally AV. Growth hormone-releasing hormone: extrapituitary effects in physiology and pathology. Cell Cycle.  Oct 15;9(20) Epub Oct

Martínez-Moreno CG, Calderón-Vallejo D, Harvey S, Arámburo C, Quintanar JL. Growth Hormone (GH) and Gonadotropin-Releasing Hormone (GnRH) in the Central Nervous System: A Potential Neurological Combinatory Therapy? Int J Mol Sci.  Jan 26;19(2). pii: E doi: /ijms

Bianchi VE, Locatelli V, Rizzi L. Neurotrophic and Neuroregenerative Effects of GH/IGF1. Int J Mol Sci.  Nov 17;18(11). pii: E doi: /ijms

Sanchez-Bezanilla S, Åberg ND, Crock P, Walker FR, Nilsson M, Isgaard J, Ong LK. Growth Hormone Promotes Motor Function after Experimental Stroke and Enhances Recovery-Promoting Mechanisms within the Peri-Infarct Area. Int J Mol Sci.  Jan 17;21(2). pii: E doi: /ijms

Yuan T1, Ying J, Jin L, Li C, Gui S, Li Z, Wang R, Zuo Z, Zhang Y. The role of serum growth hormone and insulin-like growth factor-1 in adult humans brain morphology. Aging (Albany NY).  Jan 22;12(2) doi: /aging Epub Jan

Sours: https://www.transformyou.com/cjc

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Types of Peptides: Clickable link to information on each peptide. Information below

Sermorelin Therapy in Washington, DC

Background

After Roger Guillemin and Andrew Schally were awarded the Nobel Prize in Medicine for their work on neuroendocrine releasing factors, the precise chemical structure of GHRH, a 44 amino acid peptide, was determined using tissue from human pancreatic tumors that caused acromegaly, a disease resulting from excess secretion of GH.1 The following year, Wehrenberg and Ling2 sought to determine which part of the molecule was essential for its pituitary stimulating action. By eliminating individual amino acids and then testing the remaining peptide fragments, they found that only the first 29 amino acids are needed for stimulating pituitary production and secretion of HGH. Consequently, this fragment of the native molecule, commonly known as Sermorelin is often used to treat GH deficient states in children and adults

Chemically, sermorelin is known as growth hormone releasing factor (GRF) or growth hormone releasing hormone (GRH) NH2 indicating that the amino terminus is at position However, the molecule is not used clinically as the free base, but rather as the acetic acid salt, i.e. as sermorelin acetate. The free base of sermorelin has the empirical formula CHN44O42S and a molecular weight of 3, daltons3 Sermorelin acetate is a sterile, non-pyrogenic, lyophilized powder intended for subcutaneous injection after reconstitution with Bacteriostatic Water for Injection and should be stored at between 36 and 46° F (2 and 8° C). Taxonomically, sermorelin is listed as an organic compound (kingdom), an organic acid (superclass), a carboxylic acid (class), amino acid/peptide analogue (subclass), and as a peptide (direct parent).4

Growth Hormone Replacement

Growth hormone replacement therapy (GHRT) is a regimen for treating deficiencies in children and adults whose bodies, for one or more reasons fail to produce adequate somatropin (somatotropin, human growth hormone, hGH). This hormonal deficit contributes to poor growth and development in children, and in adults fails to maintain essential aspects of bodily form and function that are needed for a healthy life of normal duration.

The medical condition resulting from inadequate production and/or utilization of hGH is called growth hormone deficiency (GHD).5 Most cases are initially observed as an endocrine disorder in children that occurs equally in males and females, although males are often diagnosed more frequently.67 Because of its significant effect on growth and development as well as causing associated medical problems and reduced quality of life, childhood-onset GHD has been treated with replacement therapy for more than 30 years. In the past, hGH therapy in children affected by GHD was stopped at the time of epiphyseal closure (i.e. at final height). This focus on height originally reflected a measure of successful GH replacement therapy (GHRT) after which treatment was ended. This was done, in part because hGH was originally extracted from human cadavers making its supply fairly limited. However, with advances in technology it became possible to clone the gene capable of producing hGH. Thereafter, the recombinant form of human growth hormone (rhGH) became available in unlimited quantities. Because of its availability for clinical application, rhGH became and is now the drug of choice, not only because of its efficacy, but also because it avoids the risk of transmitting fatal, slow viral (prion-mediated) Creuzfeldt Jacob Disease which was sometimes associated with the cadaver-derived hormone.8 Although originally indicated for use in childhood GHD, rhGH became a licensed indication for GH-deficient adults in the United States, a number of European countries, and New Zealand in This action was taken because people who had been treated with rhGH as children and then routinely discontinued from treatment upon reaching final height, experienced higher than expected rates of medical problems as adults, beginning in their 30s and 40s. These included reduced physical, mental, and social energy, excess adipose tissue, diminished muscle mass, diminished libido, poor bone density, higher than normal cholesterol levels, and elevated rates of cardiovascular disease. Research trials soon confirmed that a few months of GH replacement therapy could improve nearly all of these parameters in GHD patients. Coincidentally, it was noticed that the same intrinsic diseases as well as maladaptive changes in form and function also occur spontaneously with advancing age.9

The progressive age-associated decrements in function of the GH neuroendocrine axis are collectively referred to as the somatopause. The term represents cessation of optimal secretion of somatotropin (hGH) which is analogous to declining production of reproductive hormones during the menopause and andropause in women and men, respectively. However, there are pathophysiological differences in childhood-onset and adult-onset GHD (AGHD) when compared with progressive, age-related GHD. Initial investigations into the causes of adult onset GHD showed them to result from damage to the pituitary gland due to tumors, surgery or radiotherapy that disrupted function of the GH neuroendocrine axis.1011 Since age-related GHD is not associated with the strict and exclusive acceptance of these originally defined, causal criteria for adult-onset GHD, nor is aging generally considered a “disease”, there was and continues to be reticence to diagnose GHD in the obese and in the elderly.121314 Thus at first, little attention was paid to the fact that as the body ages, progressive dysfunction of the GH neuroendocrine system results in clinical symptoms similar to those associated with factors originally recognized as causal for GHD.

For these reasons, administration of rhGH which is the accepted treatment for GHD, has not been permitted for use in aging by regulatory guidelines promulgated by the FDA. As a result, rhGH supplementation is not approved for medical treatment of the pathophysiologic, age-related decline in GH/IGF secretion, despite the clinical similarities with classically defined, adult-onset GHD. If used at all, lower doses are recommended in the elderly to reduce the incidence of side effects and maintain age-dependent normal levels of IGF This is a confusing recommendation for the following reason. IGF-1 levels in normal young adults is higher than those in GHD adults. However, serum IGF-1 values in both groups are indistinguishable by the age of Nonetheless, the declining values in “normal” aging people are not considered to be diagnostic criteria for GHD or GH insufficiency worthy of treatment with rhGH. Instead the range of laboratory reference values are shifted downward to reflect those in human subjects as they advance in age. Surprisingly, this is a unique practice which is not done for serum values of any other hormones. Nonetheless, it restricts in part, diagnosis of idiopathic GHD and treatment with rhGH to those under 40, and thereby requires different treatments for medical issues related to age-associated, GH insufficiency. To differentiate between classically defined adult-onset and age-related GHD associated with the somatopause, the latter is often called growth hormone insufficiency (GHI). Thus, because of the similarities between GHD resulting from trauma, disease or radiation from effects of aging that occur during middle and later stages of life, endocrine therapies for treating the latter condition have been sought over the past two decades.15 In fact many years of off-label use of sermorelin, a GH secretagogue, has improved the life and health of many suffering from progressively degenerative conditions of aging.

Somatopause

Many of the body’s systems that function to maintain optimal health and well-being decline with advancing age. Aerobic capacity, muscle mass, and strength all progressively decline with age. Loss of muscle mass, or sarcopenia, and the accompanying reduction in strength increases the risk of falls and their complications, and for many individuals the associated loss of physical, functional capacity leads to increasing difficulty in living independently. Complaints of poor sleep are common in older populations. Insomnia reduces quality of life and is often a factor in decisions to seek health care. Sleep complaints often lead to overmedication and sedation of the elderly, with the numerous potential attendant problems, including increased morbidity and mortality. Finally, cognition also declines with advancing age, particularly those cognitive functions that involve novel problem solving and psychomotor processing speed, with its own related impact on the older individual’s ability to function independently.16 Aging in both sexes is accompanied by profound decreases in GH output and in plasma IGF-I concentrations. This effect is separate from the alterations in body mass index that accompany the normal aging process. Attenuation of GH output associated with aging is related by inference to reduced GH-releasing hormone (GHRH) production, pulse amplitude as well as increased somatostatin (SRIF).171819

GH secretion rates decline exponentially from a peak of about μg/kg/day during puberty to about 25 μg/kg/day by age 18 During this process there is a reduction in GH pulse amplitude, but little change in GH pulse frequency.20 There is a particularly marked decline in sleep-related GH secretion, resulting in loss of the nocturnal pulsatile GH secretion seen in younger individuals and lack of a clear night-day GH rhythm.2122 The decline in GH production parallels the age-related decline in body mass index and is associated with alterations in body composition, hormonal status, and functional capacity that mimic the changes seen in AGHD or partial hypogonadism.23 In addition to deteriorating memory and cognitive function, the changes in body composition that are most pronounced in normal aging include a reduction in bone density and in muscle mass and strength, an increase in body fat, and adverse changes in lipoprotein profiles.2425 While the aging pituitary remains responsive to GH, GHRH, and GH secretagogues, it is less responsive to stimuli such as exercise. This decline in GH production is initially clinically silent, but may contribute over time to sarcopenia and frailty. Since GH secretion declines progressively and markedly with aging, and many age-related changes resemble those of partial adult-onset GHD, stimulating production and secretion of endogenous GH with GH-releasing hormone (GHRH) or its analog Sermorelin, a GH secretagogue, could confer benefits in normal aging similar to those observed in AGHD. In particular, such treatment could reduce the loss of muscle mass, strength, and exercise capacity that leads to frailty; thereby prolonging the ability to live independently.

Secretagogues

Growth hormone secretagogues (GSHs) are a class of molecules that stimulate the secretion of GH from the pituitary gland. They include agonists of the hypothalamic and pituitary ghrelin receptors (GHRPs, ipamorelin, hexarelin, etc.), and those of the pituitary GHRH receptor such as Sermorelin.

Sermorelin is a synthetic (man-made) version of naturally occurring GHRH that is produced in the brain and can be used clinically to stimulate release of growth hormone (GH) from the pituitary gland.26 Growth hormone is necessary for growth in children and is important in adults to maintain metabolic and physiologic functions that are necessary for good health and quality of life. Thus, Sermorelin can be effective in cases of GH insufficiency and thereby sustain essential bodily functions throughout life

Clinical Applications

Some uses for Sermorelin include: Diagnosis of growth hormone deficiency/insufficiency (GHD),27 treatment of children with idiopathic growth hormone deficiency,28 management of adult-onset growth hormone deficiency/insufficiency and other conditions requiring GH replacement therapy (GHRT),2929 regeneration of pituitary function and delay its functional decline during aging2830

General Information

Sermorelin is the most widely used member of the GHRH analogue drug class. It can significantly promote the synthesis and release of growth hormone (GH) from cells in the pituitary gland, improving the serum concentrations of GH and subsequently insulin-like growth factor 1 (IGF-1) in animals and humans.3132 It is able to influence the concert of hormonal signals that affect GH secretion from the anterior pituitary including GHRH, somatostatin, and insulin like growth factor (IGF) and others. The positive and negative opposing regulation of growth hormone by GHRH and somatostatin, respectively, creates a rhythmic-circadian pattern of GH secretion.33 Thus, modification of both pulse amplitude and frequency of GH secretion results from Sermorelin administration.34 After sermorelin stimulates the release of GH from the pituitary gland, it increases synthesis of IGF-1 in the liver and peripheral tissues.34

Sermorelin acts on the growth hormone releasing hormone receptor (GHRHr) in the pituitary to regulate cellular activities. GHRHr is the natural receptor for the endogenous hormone, GHRH, and for sermorelin. This receptor regulates growth hormone release directly by stimulation and indirectly by a feedback relationships with somatostatin.35

Sermorelin is readily degraded after reaching the bloodstream, having a biological half-life of approximately min.36 Due to the biological half-life and bioavailability of Sermorelin, administration for growth in childhood GHD must occur periodically several times a day as subcutaneous-injections.37 However, single daily dosing is sufficient to treat most cases of adult-onset GH insufficiency. Three (3) mcg/kg subcutaneous-injections of Sermorelin have been reported to simulate a naturally occurring GHRH mediated GH release responses.38

In addition to increasing production and secretion GHRH also affects sleep patterns by increasing the amount of slow wave sleep (SWS) while augmenting sleep-related GH secretion and reducing cortisol secretion.39

To exert all its beneficial effects, Sermorelin requires a functioning pituitary and a host of peripheral tissues.4041 This is due to the reliance on endogenous receptors controlling hormone secreting glands and tissues. More precisely, functioning growth hormone releasing hormone receptors (GHRHr) are required on somatotrophs in a functioning anterior pituitary.40

Indications

Because of Sermorelin&#;s ability to bind receptors on somatotrophs, the pituitary cells that produce and secrete GH, sermorelin has several clinical indications and applications related to GHRH/GH insufficiency.42 For example it is officially indicated and approved for diagnostic evaluation of pituitary function and also for treatment of delayed or inadequate growth in children. It also can be used to oppose maladaptive changes in body composition such as reduced lean body mass (muscle), increased total and visceral fat, and decreased bone mass resulting from low or inadequate concentrations of serum GH and insulin-like growth factor-1 (IGF-1).

Data from research and clinical studies have demonstrated sermorelin’s multifaceted properties, some of which include:

  • Peak increases in hGH followed administration of GHRH analogs after 15 or 30 min. An increase in the integrated plasma growth hormone (GH) response was observed at each dose.43
  • Quality of life parameters including general well-being (P < ) and libido (P < ) significantly improved in men receiving sermorelin therapy.44
  • Youthful concentrations and patterns of serum hGH were restored in older persons by daily injections of GRF (sermorelin).45
  • Body composition improved after regular administration of GRF for 90 days resulting in increased muscle mass, increased total body water and decreased visceral fat.46
  • Quality of sleep improved as indicated by extended Stage IV and Slow Wave Sleep in men.47

Symptoms of Adult Growth Hormone Deficiency/Insufficiency

Adults with inadequate concentrations of serum GH can have a variety of signs and symptoms, some of which include abnormal body composition, reduced fluid volume, diminished strength, physical energy and stamina, lack of motivation, lethargy, lability etc. Symptoms of growth hormone deficiency also depend on age, and often those meeting the classic definition of adult onset GHD can have different symptoms than a child similarly diagnosed. However, those with adult-onset GHD that are causally unrelated to aging have similar clinical symptoms as those that occur progressively in incidence and severity with advancing age.48

Diagnosis of Adult Growth Hormone Deficiency

Not everyone with growth hormone deficiency/insufficiency will have the same symptoms. Some people will only have one or two while others can have multiple symptoms. Fortunately, certain tests and exams can help physicians to make an appropriate diagnosis. Exams and tests used to diagnose growth hormone deficiency are the same no matter the patient’s age.

Diagnosing growth hormone deficiency typically starts with a physical exam. The physician checks weight, height, and body proportions. Other than a physical exam, there are many other tests and exams used to make a growth hormone deficiency diagnosis.

With respect to diagnosis of adult GHD of classical etiology, guidelines state that “adult patients with structural hypothalamic/pituitary disease, surgery or irradiation in these areas, head trauma, or evidence of other pituitary hormone deficiencies are considered appropriate for acquired GHD” and that “idiopathic GHD as which occurs during aging requires stringent criteria to make the diagnosis. The reason for this restriction is that as previously described, the age-related decline in function of the GH neuroendocrine axis is accepted as being a “normal” part of aging, even though it is progressively detrimental to many aspects of body function. Thus, due to the nature of the original diagnostic criteria for GHD, and the reticence to consider aging a “disease” per se, even though disease risk, incidence and severity can be attributed at least in part to declining activity of the GH neuroendcrine axis, the criteria for determining if secretagogue therapy is indicated as an intervention in aging, are less stringent than those promulgated by Endocrine Society guidelines.15

Some or all of the following tests can be used to diagnose age related GH insufficiency, since everyone will be so affected over the course of their lives. Such diagnostic testing may be used to determine the degree to which replacement therapy is indicated, i.e., for dosing determinations. Tests include:

Blood Tests for Growth Hormone Deficiency/Insufficiency

  • Binding protein level (IGF-I and IGFBP-3) blood tests to determine whether or not the problem is caused by the pituitary gland
  • Blood tests to measure the amount of growth hormone levels in the blood
  • Blood tests to measure other levels of hormones the pituitary gland produces
  • GHRH (Sermorelin)-arginine provocative test
  • Other GH provocative stimulation tests
  • Insulin tolerance test

Other Exams/Tests to Diagnose Age-unrelated Severe Growth Hormone Deficiency

In addition to blood tests, a physican may perform some additional exams and tests to help diagnose growth hormone deficiency. These may include:

  • Dual-energy x-ray absorptiometry (DXA) scan to measure bone density.
  • Brain MRI to examine the pituitary gland and hypothalamus.
  • Hand x-rays (typically of the left hand) to examine the shape and size of bones which change as a person grows and ages. Bone abnormalities can be observed with x-ray examination.
  • X-rays of the head can show any problems with the bone growth.

If an individual experiences signs and symptoms of GHD or GHI, he/she should talk to a doctor immediately so as to perform exams and tests that assist in making an accurate endocrine analysis and diagnosis.

Treatment of GHD

While aging is not a disease, it results in significantly maladaptive changes in body composition and function which affect the individual and the community at large. While aging is associated with a milder form of adult GHD, GH replacement with secretagogues such as Sermorelin has met with success. Once daily injections can stimulate increases in GH and IGF-I at least to the lower part of the young adult normal range.49 Because peptides like Sermorelin are readily destroyed by enzymes in the digestive tract, subcutaneous (sc) or intravenous (iv) injections are the only way to administer the molecule. Since iv injections are impractical for most people, the sc route is commonly used to administer doses of Sermorelin ranging between – mg per day. The most commonly used dosage is mg daily. In a University of Washington study consisting of 6 months treatment with daily bedtime subcutaneous injections of Sermorelin, alone or in combination with supervised exercise conditioning, IGF-I levels rose approximately 35%. As with GH, subjects showed an increase in lean body mass and a decrease in body fat (particularly abdominal visceral fat).5051 Such changes indicate that regular GHRT with Sermorelin can resist changes in body composition underlying sarcopenia and frailty that lead to loss of independence. Thus, since the aging pituitary remains responsive to GH and GHS, it is reasonable that stimulation with Sermorelin is indicated in aging.52 While elders are more sensitive to GH, and thus more susceptible to the side effects of replacement with rhGH, stimulating production and secretion of endogenous GH with Sermorelin offers the advantage of a more physiological approach to increasing GH pulsatility while reducing risk for side effects.


Ipamorelin/CJC Therapy in Washington, DC

What is CJC and its use?

CJC is a synthetically produced peptide that can increase your plasma growth hormone levels. CJC is usually injected into your body via a subcutaneous injection. CJC is also sometimes referred to as DAC:GRF.  Stands for Drug Affinity Complex, and GRF stands for growth hormone-releasing factor. CJC can increase your IGF-1 levels and GH (growth hormone) levels in humans and in animals. DAC is added to this peptide in order to increase the half-life of CJC Initially CJC was developed to treat diseases and medical conditions for patients who had muscle disorders, diseases, and burn victims. CJC has drawn many individuals like athletes from around the globe for its incredible benefits and minimal side effects to enhance their performance on the field, and in the gym.

Benefits of using CJC

Lean body mass, gains in muscle mass, and increased strength. These are just a few of the benefits which CJC will deliver upon. It is a long-acting GHRH analog or  (growth hormone releasing hormone). The lifespan for releasing growth hormones is promulgated by tetrahedral modifications of CJC, and the drug affinity complex (DAC). Therapeutic effects are increased because of this, and users require fewer injections in comparison to other growth hormones. These are just a few of the benefits CJC users will appreciate in comparison to other growth hormone injections available on the market.

Side Effects of CJC

Of course many users will complain of side effects as it pertains to using supplements or injections. However, when it comes to CJC with DAC, the main CJC side effects are present as the growth hormone relates to the stimulation of the pituitary gland. An increase in vasodilation is often associated with the surge of the growth hormone into the user’s body. This typically lasts for a period of 30 minutes to 2 hours, post-injection.

Additionally, itching, pain, redness, and soreness are often noted as side effects at the injection point, although this is not reported with all users. HGH levels also increase at the cellular level once CJC is injected. Research suggests this can lead to: increased muscle strength, fat metabolism, and muscular mass. Improved skin-tone and muscle definition are also noted. For those who want to further enhance CJC with DAC effects will find that proper diet and exercise regimens will help in doing just that.

CJC Cycle: How should it be used/administered

Those who participate in studies for HGH often are given injections 2 to 3 times daily. This is typically before breakfast, before bed, and post-workout. These test periods can last up to several weeks in order to determine the actual CJC benefits on test-subjects. They are also meant to mimic as closely as possible, the actual secretion of the hormones.

The half-life of DAC is an 8 day period, and for this reason the cycles are usually shorter in duration. So the injections are only given once weekly, which result in increased GH secretion levels. Research currently doesn’t suggest that one or the other cycle delivers greater results, so it is a personal preference based upon what each user wants to use when injecting the CJC

GHRP and CJC Cycles

Growth hormone replacement peptides (GHRP 6) is typically used for synergistic effects, in conjunction with CJC For those on the weekly cycle, one evening injection of GHRP 6 is administered; this is done at night because it causes less of a cortisol surge, and prolactin, in comparison to GHRP 2. The GHRP 6 can also be used simultaneously with HGH cycles, 2 to 3 times daily, for a prolonged cycle, lasting several weeks.

Using CJC for Muscle Growth

Once adolescent growth ceases, it is difficult for the body to produce HGH in such high volumes as it did, making it harder to build lean muscle mass. HGH has helped in development of children who were deficient in the growth hormone, and this sparked a synthetic version to be created in

Several studies have since been conducted, detailing how HGH has helped build muscle mass, decrease body fat, and otherwise benefit adult users. Sometimes off-label prescription of HGH is given, particularly for athletes, the high cost, and difficulty to get a prescription, makes it otherwise difficult for adults who aren’t prescribed the injection, to be supplemented.

Research has shown that administering CJC once weekly helps to increase plasma GH concentrations ( times more) for a period of up to 6 days after injection. Further, it increases IGF-1 levels by to 3 times, for a period of 9 to 11 days, with no adverse side effects. For an athlete, those who are always on the go, or even moms who need a boost of energy, these injections can feel like users have found the “fountain of youth,” and will instantly notice a boost in energy levels.

Instructions for using CJC

The injection is non-pyrogenic, sterile, and intended for subcutaneous or intramuscular injection use. It is to be administered after reconcentration with sterile water for injection purposes. An insulin syringe can be used for subcutaneous injection, with a 2 mg CJC dosage per injection. Per vial, a 1 X 2 ml injection is to be administered.

When using .5 ml of water for mixing, this provides 2 mg dosage ( ml or 50 units in one syringe). When using 1 ml of water, this equates to 2 mg dosage (1 ml or units). The intended frequency is once weekly, with 2 mg dosage, due to the prolonged half-life.

Sample injections: Amounts to be administered

When using CJC it is important to follow proper dosage instructions. Depending on whether you are going to use the injection in the morning or evening hours, the frequency at which you will be injecting the syringe will differ.

CJC with DAC mcg should be taken once weekly.

GHRP-2, GHRP-6 or Ipamorelin Example Injection:

A nighttime injection should be given on an empty stomach (best for use at night due issues with drowsiness). It should be taken hours after your last meal.

You will inject the GHRP peptide and go straight to bed.

Example 2: Morning Injection:

You will inject mcg first thing in the morning, and wait 20 minutes prior to consuming food or beverages (including coffee/water).

There really is no guesswork as it pertains to using the CJC Of course CJC dosage, and whether you use CJC without dac (or with), will determine when, and how you administer the GHRP.

CJC Reviews: Will this benefit me?

“Four months ago, I added CJC with DAC to my cycle.” The product is legitimate, andg it worked great for me!

“After including CJC with DAC, I leaned out, noticed greater muscle growth, and definition. What more could users ask for?”

“If you are looking for an alternative to HGH injections, you’ve found it with CJC with DAC. The product is far superior.”

In addition to these reviews, it is noted that CJC has helped increase blood serum levels, of HGH, within 3 to 11 days after inception of use. The longer half-life, alongside the continual release of growth hormone, means the CJC isn’t affected by food timing. This is contrary to other peptides you might’ve used in the past.

Using CJC with DAC

When you add DAC (drug affinity complex) to CJC , you extend the half life of it by one week & it also helps you reach steadier blood levels after the injection. By adding DAC you also allow for the greater possibility of utilizing smaller Growth Hormone pules which was once thought of as a bleed, and when combined with a GHRP it can activate Growth Hormone stores the be released throughout the night at day. By stimulating cell growth, CJC will help improve skin-immunity, as well as internal organ-mass. Users further report that their sleep patterns are improved. This is essential to help in muscle development, and overall health.

The main purpose of CJC is to boost protein synthesis levels, and help fuel the growth of muscle tissues in the body. Many benefits will be derived by users who are incorporating CJC to their regimen; among these are:

  • Reduced body fat.
  • Quicker recovery times post-injury.
  • Increased muscle mass.
  • Increase in strength.

Using CJC Without DAC

If you are going to use CJC without DAC then you should know you are basically taking MOD GRF, which can be good for certain individuals that are looking to get shorter spikes of Growth Hormone release throughout the day. But if you are looking to not inject as much daily and still want to have a more powerful GH stores, then about 2- times a week you should choose to inject the CJC (with DAC). along with GHRPs that way you can reach the maximum potential of Growth Hormone release.

Will CJC cause water retention?

Because it stimulates the pituitary gland, those who are using higher doses of CJC might notice water retention in their body. Simply skip a dose, or reduce intake levels of sodium if you notice this issue. Water retention and increased levels of tiredness have also been reported by some users. After a couple of weeks, once the body has adapted, these issues typically resolve themselves. For those who notice these issues, it might be necessary to change your injection schedule, and only inject the CJC prior to bedtime, as opposed to in the morning hours.

CJC Proper Dosage

Modified GRF (CJC without dac): mcg per injection. Each vial contains 20 X mcg doses.

Injection amount: If using 1 ml of water for mcg dosage – use ml per syringe when injecting. For 2 ml of water, .1 ml will be used per syringe.

Frequency: mcg should be injected 1 to 3 times daily, best if injected with to mcg of GHRP peptides.

CJC with DAC: Take mcg once weekly, at any time.

Modified GRF frequency: Inject 1 to 3 times daily, best when used with to mcg GHRP peptides.

How to inject CJC

For best results, subcutaneous injections are suggested. Wash your hands and gather all materials, also clean the vial with alcohol prior to injection. Simply use an insulin syringe so you can extract the desired dosage, and tap/flick the syringe, so you can remove unwanted bubbles.

To prevent infection it is best to use an alcohol pad to wipe the skin prior to injection. Gently insert the needle into the fat, and inject the contents in the syringe. Once completed, wipe the injection site with alcohol, and dispose of the syringe.

CJC with Ipamorelin

CJC with DAC is often used alongside Ipamorelin because of the synergistic effects, and increased GH release levels. If you are on the CJC weekly cycle, you will include Ipamorelin evening injections (again, this may cause drowsiness). This will decrease cortisol and prolactin levels, in comparison to GHRP 2 and GHRP 6. You can also use Ipamorelin with stacked HGH, 2 to 3 times weekly, for prolonged cycles (as detailed above).

Research using Ipamorelin of to mcg dosage, 2 to 3 times daily with subcutaneous injections

It is best to begin with lower dosage, to reduce the side effects (typically rush/headaches). It is best to inject 20 to 30 minutes pre-workout, because of the pulse in growth hormone, it will produce the best results. Ipamorelin will work slower than GHRP, so spikes in GH levels isn’t as noticeable as quickly. The slower release is natural and has prolonged effects. Further, for those who are on restricted, calorie intake diets, there is no report of increased hunger levels using Ipamorelin or GHRP 6.

Is it normal to be flushed with CJC?

Using mcg per injection, most people respond well to the CJC injection. Head rush, or throbbing headache/pain, are the most commonly reported side effects by users upon administering the injection dosage. This may start 10 minutes post injection, and last for a period of up to 20 minutes.

This isn’t a serious side effect, and is attributed to the release of GABA (gamma-aminobutyric acid), which is a neurotransmitter. This is seen as a good/positive sign by users, as it indicates peptides are working, and HGH release is occurring in the body.

Is CJC better than HGH?

The answer is yes. Absolutely, CJC with DAC is far superior to the results you will experience in using HGH injections. The simple fact that CJC causes an increase in HGH levels and production, as well as stimulates production of IGF-1, are benefits most HGH products won’t produce.

As an added benefit, CJC is cheaper when purchased through Absolute Pharmacy than HGH supplements. You will also realize the same body fat loss levels, increased muscular development, and increases in natural strength.

Considerations when ordering CJC

Regardless of the benefits you are trying to achieve, increasing growth hormone levels is beneficial to those who are working out routinely, and on a balanced diet. Not only will you realize an increase in muscle mass and lean mass development, you are also going to notice reduced body fat levels upon using CJC routinely.

Due to the nature of studies conducted, the usage and dosage each individual will administer, is up to them. It is important to however consider the fact that drowsiness, and headaches, are possible side effects to using the CJC with DAC. For this reason, it is important to test both nighttime use (once weekly), or morning use (2 to 3 times daily for a few weeks), to determine which works best for you.

The results you are going to see should be similar whether you are administering injections in the morning or evening hours. But, it is important to follow proper dosage instructions for safety, and for optimal results in muscle development, lean muscle mass, and to decrease body fat levels when incorporating CJC as a part of your diet and exercise regimen.

Increasing HGH release levels in your body naturally. It sounds too good to be true, but what if you could achieve just that by using a supplement? Using Ipamorelin alongside your exercise and diet regimen is going to help you achieve said goal. No two users are alike. For athletes or those who workout religiously, you might experience greater results than an individual who is overweight and just getting back into the gym after 10 years. So, take it with a grain of salt when detailing the results below. Dosage, your body composition, and other factors will play a role in the results you can expect to see when you incorporate Ipamorelin.

Now that you have an idea of what it can do for you, let’s delve into the dosage, possible side effects, proper use, and anything else you should know as a athlete, or individual who simply wants to naturally increase lean muscle mass, by introducing Ipamorelin into your system.

Ipamorelin Dosage

Ipamorelin is a growth releasing hormone; what this means is that if your body doesn’t produce enough, or if you are deficient, supplementing with Ipamorelin can help. It can be used as an alternative to GHRP-2 or GHRP Users will experience similar results and gains, minus the documented side effects which are common with these two supplements.

to mcg is typically the daily dosage which is recommended for the typical Ipamorelin user. It can be taken anytime during the day, but is advisable to be used in the morning, as it will help you achieve the best results in such cases. Regardless of when you start your dosage, it is important to ensure you are taking it at the same time each day. And, for new users, it is best to stick to a one-a-day cycle.

If you are a athlete, if you are used to working out regularly, or if you have already used the supplement in the past, it is possible that you can hike-up the recommended dosage levels. You can take the supplement times per day, at the same mcg dosage levels you would take with a single dose each day.

Ipamorelin Dosage Cycle

When you are just getting started with Ipamorelin, it is advised to use only one supplement daily at the same time each day. It is also advised to begin on the lower end, typically an eight week cycle, and at a maximum twelve week cycle. Doing this not only guarantees the desired results when using Ipamorelin, it is also going to ensure you get the most out of the supplement. When using at this dosage cycle you will:

  1. Increase muscle growth and development, and decrease body fat levels naturally.
  2. Realize an increase in energy levels throughout the course of your day.
  3. Natural increase in HGH levels, which is beneficial, as these levels dissipate naturally as you get older.

It does not matter what your intended use it; whether it is for weight loss, muscle mass development, lean muscle mass, or simply to increase HGH to their natural levels, you should always maintain the same dosage levels throughout the entire cycle. Do not increase use if you believe you aren’t achieving the results you are hoping for, as this can result in negative side effects, or lackluster results.

Timing Dosage: Why it matters

When taking Ipamorelin, you want it to be pushed through your system naturally, and at the same levels. If you are constantly altering the times you take it, or increase/decrease dosages during your cycle, this is not going to be attainable. To maximize the benefits and gains you are going to experience, dosage levels should be consistent, as should the timing of the dosage you are taking each day.

This can also potentially decrease the likelihood that you will experience adverse or negative side effects with use. It is also best to use your Ipamorelin injection when you are going to eat a meal; you won’t feel it, and it is easier to flow through your bloodstream when it is taken as such.

The Results: What Benefits Can I Expect?

As we mentioned above, the results you are going to realize are different for each user. A athlete might see immediate and greater gains, than a year old male who has never stepped foot in a gym and is 30 pounds overweight. So, make sure you bear this in mind as you are determining whether or not Ipamorelin is right for you. Further, if incorporating other supplements like CJC or additional growth hormones, the results are also going to be greater than if you are simply using Ipamorelin on its own. Make sure you are aware of this, and how to properly incorporate it with other supplements, in order to ensure the best possible results with use.

Depending on the intended use, and your desired results, the dosage levels are going to vary from person to person as well. So, keep this in mind when trying to determine how great the results are actually going to be when you are using Ipamorelin. So, what exactly can you expect when using this supplement? Some things you will see, for every user is:

  • An increase in growth hormone levels. These are naturally released by the pituitary glands, and as your body stops producing the hormone as you age, a supplement, such as Ipamorelin, can naturally help increase those dissipated levels.
  • If using it with CJC , you can experience a correlation in increased muscle mass levels. With longer release periods, greater results are achievable. So, if you want to gain more muscle mass, or if you simply want to increase levels of lean muscle mass, you are going to realize these possibilities when you incorporate the use of Ipamorelin into your daily regimen.
  • Less downtime. You will recover faster, your body will recuperate faster, and you are back on your feet faster. So, you won’t experience as much downtime after a tough workout, letting you get back to your regimen faster.
  • Faster weight loss is achieved. Increase in lean muscle mass, increase in metabolic rate, and increase growth hormones, all work together to help you burn more calories, and conversely lose more weight in less time.
  • Your skin, nails, and hair will look better. It can work to help fight the signs of aging, and you are going to look and feel younger. A younger, more jovial appearance is almost instantly realized among users who incorporate Ipamorelin to their workout and diet regimen.

No growth hormone, or any supplement for that matter, is never going to equate to the same exact results for every user. So, what you experience, is not the same as the next user, and vice-versa. Further, the increase in results and how quickly you will see these results are going to differ for each user. So, make sure you understand this prior to starting your dosage, to ensure you are not disappointed if you do not see each one of these benefits, on the very first day that you begin using the Ipamorelin. Also consider the fact that if you use it after food, or with a meal, results will improve. So, proper timing, and proper diet and exercise regimen can greatly enhance the results you are going to realize when you are using Ipamorelin as well.

Cycling: How Should you take Ipamorelin?

 

An 8 to 12 week cycle is typically advised for new and for more experienced (repeat) users of Ipamorelin. If you are using it for the first time, it is advised to stick to a shorter 8 week period, to see how the results pan out, and also to determine if it is going to cause adverse side effects you experience.

This duration is a sufficient time to allow the ghrelin peptide to work through your system, and also for it to have a long lasting effect with continued use. It will work to enhance the hormone system, increase the metabolic rate, and increase lean muscle tissue levels in this period of time. As discussed above, the proper dosage for new users is to mcg daily, at the same time each day. For more experienced users, you can take the same dosage, 2 to 3 times a day (remember that it is the same time each day, and is best to use your injection after a meal for the best results possible).

Ipamorelin & Athletes: What benefits will you see?

As a athlete, incorporating a growth hormone like Ipamorelin is extremely beneficial. Not only in the development of lean muscle tissue and muscle mass, but also in the decreased recovery time you are going to experience after each workout. You can workout more, you can workout and lift harder, and you can increase your level of exertion at the gym to experience the greatest gains, as your body is going to heal much faster than it would without the growth hormone.

As a athlete, you can also increase your dosage cycle for a period of 12 to 16 weeks at a time, to maximize your gains. Do so gradually if you opt to go this route. Make sure you increase your daily dosage (1 to 2 doses per day, etc.) gradually. Start off with lower dosage levels as well, and see how it interacts with your body. You don’t want to experience withdrawal, nor do you want to exprience negative side effects when using Ipamorelin for longer dosage cycles. So, make sure you monitor your progress, see how you feel as you go, and make notes if/when you do experience negative side effects, so you can balance down to the proper dosage levels.

When you increase the dosage gradually it is also going to ensure you do not experience all (or any) of the noted side effects which are possible with the use of Ipamorelin. And, if you are taking other peptides, supplements, or growth hormones, it is the best way to ensure they are going to acclimate well, and work together well, in order for you to realize the greatest results possible when trying to increase muscle mass, and lean muscle tissue, without putting on body fat in the process.

Ipamorelin: First time user?

For those who are just getting started, make sure you go gradually. Start off with an eight week cycle, and start off with mcg (rather than ) per day. Doing a test run will allow you to see how your body is going to react. If all goes well, you can then increase your dosage cycle to an 8 to 12 week period, and possibly add an additional injection dose daily, or increase to mcg with each use.

It is a trial and period session you will go through when you are new to Ipamorelin use. And, when you monitor use, properly incorporate it, and make sure you increase the dosage gradually, rather than all at once, it is going to ensure the best results, and the safest use, for new users to the supplement.

You’re not like the next person

It is also important to note that whether you are a long-time user, or a first-time user of Ipamorelin, your body is going to react differently to that of the next user. Like the benefits you will experience, the side effects you are going to experience will occur differently, and at different dosage levels. So, it truly is a trial and error period you are going to go through with a test run of Ipamorelin for new users. You have to find what works for you, how your body will react, and what potential side effects are lingering ahead, in order for you to achieve the greatest results, and eventually find the proper dosage and cycle level, which is going to work the best for your body and system.

Alternative Uses of Ipamorelin

There is no “one right way”, to use Ipamorelin. For example, if you are using to mcg doses daily, twice a day, your cycle might run for an 8 week period. If on the other hand, you are a athlete training for a competition, you might be on 3 injections per day, at mcg, and will stay on for a 12 week period. For new users, you might find a mcg injection is too high, and you will cut back to mcg until your body gets used to it, for an 8 week cycle.

You will learn that no single method of using Ipamorelin is right or wrong, and there is more than one route (and dosage cycle length) you can choose, when you do incorporate Ipamorelin into your diet and exercise regimen. Regardless of how high or how long the dosage cycle is, you want to start off on the lower end when you are new to using Ipamorelin, or any growth hormone for that matter. Not only will this reduce the potential risk of experience the side effects, it also ensures your body will ingest the highest levels into the bloodstream. And, it will allow you to gradually increase dosage and cycle lengths, in order to eventually get to the ideal levels which work best for your body, and for the intended/desired goals you are trying to achieve when using Ipamorelin daily.

Proper Use  of Ipamorelin

When using Ipamorelin, you obviously want to use it properly. So, let’s go over a few of the ways in which you can use it, to achieve the best results.

Weight loss

With a blend of peptide and GH supplements, Ipamorelin can greatly help you in your weight loss endeavors. Using it with IGF-1 which is a natural growth hormone, can help you achieve even greater results. With lower dosage, you won’t increase muscle mass, your body will naturally decrease body fat levels, and you will begin to metabolize food faster, meaning you burn more calories in less time, for greater weight loss results.

Muscle mass gains

Athletes will greatly benefit from using Ipamorelin. For example, if you use CJC along with Ipamorelin, the results are going to be even greater. HGH increase will result in greater muscle mass levels, less time for muscle mass to develop, and increased levels of lean muscle tissue. The more peptides your body produces, the greater your lean muscle mass is going to be. And, over time, with gradual increases in HGH, you are going to realize a leaner, more muscular definition to your body.

Anxiety

If you suffer from anxiety, Ipamorelin can possibly help you reduce levels of anxiety as well. It can serve as a natural relaxant. It will help relieve and soothe the muscular system, so you will naturally feel a calming-effect when taking proper doses of Ipamorelin.

Anti Aging

Ipamorelin can serve as a natural anti-aging solution. It is a growth hormone, and along with a peptide blend, can naturally help increase elasticity in the skin. Your nails, hair, and skill will look younger in no time at all.

Fat loss

Yes, Ipamorelin can help you lose weight. But, if you are not exercising, and aren’t eating well, it can only do so much. There is no magical supplement which will undo laziness and a horrible diet – keep this in mind. When using it for fat loss, make sure you are exercising. Doing so will naturally increase weight loss results, as you are going to burn more calories, along with the caloric deficit you are already on, for greater results. Further, your diet matters. If you are eating calories of junk per day, no supplement will help you lose weight – no matter how potent it claims to be!

Benefits & Possible Side Effects

We’ve gone through several benefits of using Ipamorelin; among these are:

  • Weight loss in greater amounts and development of lean muscle mass.
  • Muscle growth and development.
  • Anxiety reduction, and improved appearance of skin (anti-aging formula).

Greater energy levels are also possible. Increasing growth hormones will naturally help add that “pep to your step” that you’ve lost. Remember, results will vary for everyone.

Some of the side effects you might experience will include:

  1. Increased cortisol levels – This is typically with higher doses and longer dosage cycles.
  2. Head rush/headache – This is often linked to higher dosage levels.
  3. Nausea/upset stomach – This might ensue in individuals who suffer from digestive issues, or when taken at higher dosage levels.

Speak to your doctor prior to use. They are the only one that can tell you if Ipamorelin is safe, and is proper for you to be using. Further, they will explain side effects, and what you should do in the event you do experience them.

Is Ipamorelin for me?

Weight loss, muscle growth, those who feel ‘depleted’, or if you simply want to increase loss of growth hormone production levels, Ipamorelin can help. If you fall into any of these categories, you are a candidate for use. You should still speak to your doctor prior to use. Not only will they explain possible complications or side effects, they will inform you of proper dosage, cycle, and how to use Ipamorelin.

Keep in mind the results will vary. Every user is going to experience different gains and benefits, at different levels. So, don’t compare your results to another user of Ipamorelin, as the results are not going to be the same.


BPC Therapy in Washington, DC

Adding supplemental boosters to your daily health routine has been the path many people have taken. Products such as protein powder, amino acids and pre workout compounds are just a few. Another group of supplements is called peptides. Peptides are essentially a chain of amino acids that benefit the body and its functions. Peptides are plentiful and have been shown to benefit a persons health, fitness and well-being. One of the newer peptides on the market is called BPC BPC stands for body protective compound and studies have shown that this peptide does just that. This compound is actually derived from the gastric liquids found in the stomach. Research has shown BPC to have considerable biological healing properties. In other words, it helps the body heal. It was originally developed to help heal inflammatory bowl disease and gastric ulcers. This makes sense since it comes from the stomach. This is not just a supplement for people with stomach issues.

Other studies when BPC was used showed benefits for healing torn or damaged muscles, tendon to bone healing and general protection for our organs. Many people have successfully used this peptide to heal bleeding ulcers caused from NSAID overuse. This peptide can be very useful to athletes or just the average person who has daily aches or injury. Overuse of our body can cause muscle, tendon and ligament issues that affect our everyday life. The addition of BPC can help heal the sore knees, pulled hamstring or sprained ankle. The most common and effective way to administer this peptide is by injection or transdermally. Fortunately a transdermal skin patch with BPC is on the market ready to help with what ails you. Simply stick a patch on your arm, wrist or stomach and reap the rewards of this healing compound.

PT (Brem Therapy in Washington, DC for Men

PT was developed from the peptide Melanotan 2, which is a synthetically produced variant of a peptide hormone naturally produced in the body that stimulates melanogenesis that is known as an alpha-Melanocyte stimulating hormone. PT has been shown in studies to provide libido-enhancing effects by activating the melanocortin receptors MC1R and MC4R, without tanning the skin.

What is PT?

PT was developed from the peptide Melanotan 2, which is a synthetically produced variant of a peptide hormone naturally produced in the body that stimulates melanogenesis that is known as alpha-Melanocyte stimulating hormone. PT has been shown in studies to provide libido-enhancing effects by activating the melanocortin receptors MC1R and MC4R, without tanning the skin.

PT is a potential remedy for the treatment of female sexual dysfunction and male erectile dysfunction.

Studies have shown that PT does not act on the vascular system, but may increase sexual desire through the nervous system.

Patient Benefits Over Time May Include:

• Improves female sexual arousal disorder
• Improve sexual function in men (such as erectile dysfunction or impotence)

Typical Prescribing Protocol for Men:

Males with no history of ED may begin with 1mg (mL) via subcutaneous injection in the lower right quadrant of abdomen at least 45 minutes prior to sexual activity (titrating dose upward to effect as needed or tolerated).

Males with a history or diagnosis of ED with inadequate response to Sildenafil mg may begin with 4mg (mL) via subcutaneous injection in the lower right quadrant of abdomen approximately 45 minutes prior to sexual activity (titrating dose upward to effects as needed or tolerated).

PT (Brem Therapy in Washington, DC for Women

What is PT?

PT was developed from the peptide Melanotan 2, which is a synthetically produced variant of a peptide hormone naturally produced in the body that stimulates melanogenesis that is known as alpha-Melanocyte stimulating hormone. PT has been shown in studies to provide libido-enhancing effects by activating the melanocortin receptors MC1R and MC4R, without tanning the skin.

PT is a potential remedy for the treatment of female sexual dysfunction and male erectile dysfunction. Studies have shown that PT does not act on the vascular system, but may increase sexual desire
through the nervous system.

Patient Benefits Over Time May Include:

• Improves female sexual arousal disorder
• Improve sexual function in men (such as erectile dysfunction or impotence)

Typical Prescribing Protocol for Women:

Females with FSAD or HSDD may begin with mcg – 1mg (mL – mL) via subcutaneous injection (titrating dose upward to effect as needed or tolerated) at least 45 minutes prior to sexual activity. Recommended to use no more than two times per week.
Side effects may include: nausea, flushing and headache.
Prostate Cancer Treatment: High Dose IV Vitamin C

High Dose IV Vitamin C:

At low concentrations Vitamin C is an antioxidant and protects against free radical damage which can lead to the development of cancerous cells. At high dosages, Vitamin C becomes oxidative and researchers have discovered that a highly-concentrated dose of vitamin C is &#;selectively&#; toxic to cancer cells, meaning the high dose of vitamin C harms cancer cells but not healthy tissue. Moreover, when this treatment is coupled with the addition of the enzyme catalase, the cancer-killing effect of the treatment was reduced significantly. This led researchers to believe that the high dose vitamin C infusion resulted in the production of large quantities of hydrogen peroxide, which initially caused a cancer killing effect that was then neutralized by the addition of the enzyme catalase. This suggested that cancer cells do not produce a sufficient amount of catalase to neutralize high levels of hydrogen peroxide on their own.

In fact, we now know that a large number of cancer cells produce small amounts of catalase in order to sustain low concentrations of hydrogen peroxide. This creates the cancer friendly environment of mild oxidative stress that encourages malignant cells to grow rapidly and become more aggressive. Fortunately for everyone, because a high proportion of cancers are only able to produce small amounts of catalase, they are very vulnerable to the cancer-killing effect exhibited by high levels of hydrogen peroxide.

The research at the National Institutes of Health has proven that in order to consistently achieve the concentration of vitamin C sufficient to provoke oxidation, a patient must receive dozens of grams of intravenous infusions of vitamin C. Oral administration is completely ineffective in this regard. A number of published case reports show that repeated high-dose intravenous vitamin C treatments yield objective tumor regression. These case reports are so compelling that intravenous vitamin C therapy is currently being formally evaluated in clinical trials at the NIH.

In theory, high-dose vitamin C therapy should not cause toxic damage to healthy tissue because the body produces sufficient amounts of catalase to efficiently neutralize the hydrogen peroxide produced. Our experience in the real world certainly supports the theory. We have treated hundreds of patients in this manner with no side effects. Our current protocol insures blood and tissue levels of vitamin C that are safe and effective to kill cancer cells.

Yet, a burning question still remains. Why hasn&#;t this therapy worked for everyone? There are three variables that can undermine the effectiveness of this therapy. First, some tumors produce larger amounts of catalase which neutralizes the oxidizing effect of hydrogen peroxide. Second, sometimes there are an insufficient number of catalysts to promote the transfer of electrons. Third, sometimes there is an insufficient amount of oxygen in the extracellular space, which is needed in order for vitamin C to produce hydrogen peroxide.

For now, scientists have not found a way to selectively block the production of catalase within tumors. However, we can definitively increase the effectiveness of this therapy by providing two supporting agents—electron transfer catalysts and tumor oxygenating agents.

Sours: https://www.bhmcnd.com/services/peptide-therapy/


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