- 10-18-2006, 02:43 PM
CJC-1295 is a Long acting GHRH analog. Growth-hormone-releasing hormone (GHRH), also known as growth-hormone-releasing factor (GRF or GHRF) or somatocrinin, is a 44-amino acid peptide hormone produced in the hypothalamus by the arcuate nucleus. GHRH stimulates growth hormone (GH) secretion from the pituitary. GHRH is released in a pulsatile manner, stimulating pulsatile release of GH respectively.
In addition, GHRH also promotes slow-wave sleep .
The active portion of this GRF or GHRH peptide can be found as a 29 amino acid long peptide and is appropriately named GHRH1-29. This pulsatile release of various peptides is due to the negative feedback loop that is part of the hGH axis and controls the amount of hGH that your body produces to keep it in a homeostatic environment. Despite the effectiveness of GHRH to stimulate growth hormone release there are a number of problems associated with using it in vivo. The most noteworthy problem is the half life of the peptide, which has been shown to be ~7 minutes using advanced HPLC technologies that have proven to be very accurate. The reason for this relatively short half life is due to an enzyme called dipeptidylaminopeptidase IV (DPP-IV), which has a high affinity for the amino acids Ala and Pro and in the case of GHRH it cleaves the 1 and 2 positions that consist of Tyr-Ala, creating GHRH3-29, an inactive form of the peptide. To prevent the problems associated with natural GHRH, pharmaceutical companies looked at new ways to increase the half life and bioavailability of these smaller peptides with technologies that work far different than other technologies, such as PEGylation.
CJC-1295 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. By applying the Drug Affinity Complex (DAC) technology to GRF, the peptide selectively and covalently binds to circulating albumin after subcutaneous (SC) administration, thus prolonging its half-life. These substitutions are key in increasing the overall half life of CJC-1295 but there lies an even greater reason as to why the half life has been extended from ~7 minutes to greater than 7 days! Bioconjugation is a relatively newer technology that takes a reactive group and attaches it to a peptide, which in turn reacts with a nucleophilic (usually a partially negative molecule) entity found in the blood to form a more stable bond. Albumin, one of the most abundant substances in the human body is chosen as the nucelophile by this particular peptide thanks to a Cys34 thiol group that attracts it. By combining the tetrasubstituted GHRH analogue with maleimodoproprionic acid using a Lys linker, you create a GHRH peptide with a high binding affinity for albumin. Once the CJC-1295 molecule has attached itself to albumin, it is given an extended half life and bioavailability thanks to the albumin preventing enzymatic degredation and kidney excretion. In fact, bioconjugation is so effective that there was less than 1% of CJC-1295 left unreacted in vivo and over 90% was stabilized after subcutaneous injection. This means that you get more of what you paid for working for you. There was no DPP-IV degredation observed on CJC-1295 in any of the various experiments conducted.
Various experiments have been conducted to test the effectiveness of CJC-1295 in vivo and the Journal of Clinical Endocrinology & Metabolism has reported dose-dependent increases in mean plasma GH concentrations by 2-10 fold for more than 6 days and increased IGF-1 concentrations 1.5-3 fold for 9-11 days after a single injection!
(from the same study) Subcutaneous administration of CJC-1295 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
Not only that but they proved the mean half life to be 5.8-8.1 days and after multiple doses showed mean IGF-1 levels remained above baseline for up to 28 days following! No serious adverse reactions were reported in any group.
Because of the long half-life and stability of the CJC-1295 analog it may only need to be taken 1-2 times per week. However research on GHRH knockout mice showed that e/d injections where superior in increasing GH vs every 48 or 72 hours. “GHRHKO animals receiving daily doses of CJC-1295 exhibited normal body weight and length. Mice treated every 48h and 72h reached higher body weight and length than placebo-treated animals, without full growth normalization.” These mice were treated for 5 weeks.
However the flaw in this study appears to be that the mice treated e/d were receiving a larger dose, so at minimum cjc-1295 is dose dependent. Whether or not a more frequent injection would prove to be beneficial is yet to be determined.
- 10-18-2006, 04:05 PM
10-18-2006, 04:20 PM
220lbs is exactly 100kgOriginally Posted by endless
so 30X100 would = 3000µg
or 60X100 would = 6000mcg
Because of the seeming build-up of this peptide over time however taking smaller doses for a long period should raise the levels of GH significantly. I have yet to test it myself.
10-18-2006, 04:50 PM
10-18-2006, 05:11 PM
What dosing protocol will your hamster be following when you do test it?Originally Posted by TheGame46
10-20-2006, 03:56 PM
Unfortunantly there is going to be a delay in that b/c of some issues with thei clinical trail, but I plan on using 1-2mg per week possibly split into two doses. I'll prob start low and see how the rats react
10-20-2006, 03:56 PM
There has been some issues during the CJC clinical trails resulting in what appears to be a temporary hault in the trail. It seems very likely that the trail will be resumed but Innovative Research has decided to hold off on distributing this product for the time being.
Here is the news direct from the pharmaceutical company’s (ConjuChem) press release after the incident
Lipodystrophy study halted after patient death
A Phase II study of a lipodystrophy treatment developed by Canadian
biotech company, ConjuChem, has been halted after the death of a study
participant. The cause of death and its relationship to the study drug -
CJC-1295, a chemically modified version of growth hormone releasing
factor (GRF) also known as DAC:GRF - is currently being investigated.
However, a Phase III study of another Canadian-developed GRF-based
lipodystrophy treatment, Theratechnologies' TH-9507, is continuing.
The multicentre, randomised, placebo-controlled, double-blind Phase II
study of CJC-1295 had only completed enrolling a total of 192
participants with HIV-related visceral obesity at various sites in North
and South America last month. Participants were randomised to receive
once-weekly injections of either a three-week escalating low dose of
CJC-1295 (at 60, 90, 120mcg/kg); a three-week escalating high dose (at
60, 120, 240mcg/kg); or a placebo, and then continue for a further nine
The only information released so far by ConjuChem, which stopped the
study on July 17th, is that the participant who died was attending a
study site in Argentina. An unconfirmed, anecdotal report from a trial
participant at a Canadian study site, suggests that the individual
concerned was a man who died a few hours after receiving his eleventh
Here is the results of the investigation regarding the death of the man participating in the trail.
ConjuChem provides findings of DAC(TM):GRF HIV Lipodystrophy trial investigation
ConjuChem Biotechnologies Inc. provided findings of its investigation into the death of a patient that occurred in its Phase II clinical trial of DAC(TM):GRF in HIV Lipodystrophy.
MONTREAL, Canada | Aug 08, 2006 | ConjuChem Biotechnologies Inc. (TSX:CJB) provided findings of its investigation into the death of a patient that occurred in its Phase II clinical trial of DAC(TM):GRF in HIV Lipodystrophy. The Company had previously reported on July 14 that a death occurred of a patient in the trial at a clinical site in Argentina. The trial was an international multi-center, randomized, placebo-controlled, double-blind study which had completed enrollment with 192 patients.
Patients were to be administered once-weekly dosing of DAC(TM):GRF for 12 weeks followed by a 6-week follow-up. The deceased patient received the 11th weekly dose on July 13 and approximately two hours later, the patient complained of chest discomfort and an ECG confirmed an acute myocardial infarction; death occurred approximately one hour later.
There is no evidence of any cardiotoxic effects of DAC(TM):GRF in previous preclinical or clinical studies. The attending physician stated that his most likely explanation for the event was the patient had asymptomatic coronary artery disease with plaque rupture and occlusion.
ConjuChem indicated it has terminated the Phase II study and is further evaluating the clinical development strategy of DAC(TM): GRF.
As you can see, it appears that the CJC-1295 peptide had nothing to do with death of the man in the trial. He was an obese AIDs patient as all the other participants. The autopsy showed positive ECG results for the heart attack and further investigation confirmed large amounts of plaque in the arteries as said above leading to the eventual heart attack. It happens everyday unfortunately, especially in the overweight population.
The CJC peptide and the GRF from which it is derived have shown no potential risk factors, and no cardio toxic effects. In fact a competing company was doing a similar study and has continued it trail right through the incident. That alone should show the confidence that this was a totally random, isolated and unrelated incident from the clinical trail of the CJC-1295 peptide. It is still however the wishes of Innovative Research to hold off on releasing the product at least for a short period of time.
10-20-2006, 05:02 PM
Correct me if I'm wrong, but with this study design isn't it also possible this guy was getting the placebo all this time and then croaked?
10-20-2006, 05:06 PM
its possible, however ConjuChem has not mentioned any details of what this participant was actually receiving. I find it hard to believe they would have haulted the trial if he died taking the placebo. They definantly would have said something about it to reassure their investorsOriginally Posted by CDB
10-24-2006, 02:26 PM
Originally Posted by endless
No bro is 30mcgs to 60mcgs per kilo meaning 3mgs to 6mgs once or twice per week at least.
Check this out:
J Clin Endocrinol Metab. 2005 Dec 13
Prolonged Stimulation of Growth Hormone and IGF-1 Secretion by CJC-1295, a Long-acting Analogue of Growth Hormone-Releasing Hormone, in Healthy Adults.
Sam L Teichman, Ann Neale, Betty Lawrence, Catherine Gagnon, Jean-Paul Castaigne, Lawrence A Frohman
Context: Therapeutic use of growth hormone-releasing hormone (GHRH) to enhance GH secretion is limited by its short duration of action. Objective: To examine the pharmacokinetic profile, pharmacodynamic effects, and safety of CJC-1295, a long-acting GHRH analog. Design: Two randomized, placebo-controlled, double-blind, ascending dose trials with durations of 28 and 49 days. Setting: Two investigational sites. Participants: Healthy subjects, ages 21 to 61 yr. Interventions: sc administration of CJC-1295 or placebo in one of 4 ascending single doses in the first study and in 2 - 3 weekly or biweekly doses in the second study. Main Outcome Measures: Peak concentrations and area under the curve (AUC) of GH and IGF-1; standard pharmacokinetic parameters for CJC-1295. Results: After a single injection of CJC-1295, there were dose-dependent increases in mean plasma GH concentrations by 2-10 fold for >/= 6 days and in mean plasma IGF-1 concentrations by 1.5- to 3-fold for 9 - 11 days. The estimated half-life of CJC-1295 was 5.8 - 8.1 days. After multiple CJC-1295 doses, mean IGF-1 levels remained above baseline for up to 28 days. No serious adverse reactions were reported. Conclusions: sc administration of CJC-1295 resulted in sustained, dose-dependent increases in GH and IGF-1 levels in healthy adults and was safe and relatively well-tolerated, particularly at doses of 30 microg/kg or 60 microg/kg. There was evidence of a cumulative effect after multiple doses. There was evidence of a cumulative effect after multiple doses. These data support the potential utility of CJC-1295 as a therapeutic agent.
I have seen the study also when they refer as to Ugs but I think is the same as MCG, I'll look for a chart to double check.
10-24-2006, 02:32 PM
Originally Posted by Maradonayes its mcg, and yes we answer'd his ? correctly so what's the "NO bro" for????Originally Posted by TheGame46
10-24-2006, 02:49 PM
My guess is he typed before he thought because he saw what the price would be for a research study over a reasonable time range at that dosage for a 220lb hamster.Originally Posted by TheGame46
10-24-2006, 03:31 PM
My bad, I missed that part when you answered it, BTW is 3mgs to 6mgs the recommeded dosage once per week?
I just found that information earlier this morning among other useful information about these wonderful peptides.
10-24-2006, 04:24 PM
I quoted that exact study in the profile.Originally Posted by Maradona
I am now sure what the recommended dose is going to be yet. there has been some debate.
10-24-2006, 05:09 PM
09-08-2007, 12:35 AM
09-08-2007, 12:53 AM
The LORD is my rock, my fortress, and my savior; my God is my rock, in whom I find protection. He is my shield, the power that saves me, and my place of safety.-Psalm 18:2
09-08-2007, 12:56 AM
09-08-2007, 01:05 AM
09-08-2007, 01:11 AM
09-22-2007, 12:50 PM
09-28-2007, 10:32 AM
bump////// anyone using this stuff and any comments on dosage?
Everything I can find for studies shows the need of at least 6mg / week or more.
10-02-2007, 02:28 PM
WELL I JUST GOT THE PRODUCT MY SELF AND IAM GOING TO START ON IT TWICE A WEEK AND I WILL POST THE RESULT TO SEE WHAT HAPPEN , :dl: :dl:
10-02-2007, 05:54 PM
10-02-2007, 07:31 PM
10-03-2007, 09:40 AM
10-06-2007, 02:49 PM
10-07-2007, 07:26 PM
10-28-2008, 04:17 PM
10-28-2008, 04:37 PM
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