CJC-1295 (No DAC) dosing & administration

Teichman et al. · 2006

Single injection increased GH levels 2-10 fold for 6+ days and IGF-1 levels 1.5-3 fold for 9-11 days. No serious adverse events were reported in healthy adults.

Ionescu M, Frohman LA · 2006

CJC-1295 increased GH secretion while preserving the natural pulsatile pattern. Basal GH levels increased 7.5-fold and IGF-1 increased 45% one week after injection.

Alba M, Fintini D, Sagazio A et al. · 2006

Daily CJC-1295 treatment restored normal body weight, length, and body composition in growth hormone-deficient mice, demonstrating its ability to normalize GH-dependent growth.

Sackmann-Sala L, Ding J, Frohman LA et al. · 2009

CJC-1295 administration caused measurable changes in serum protein profiles, indicating activation of the GH/IGF-1 axis with potential biomarkers of GH activity.

Frohman LA, Downs TR, Heimer EP, Felix AM · 1989

Human GHRH, including the 1-29 fragment, is cleaved rapidly in plasma at the bond between amino acids 2 and 3 by the enzyme dipeptidyl peptidase IV, which inactivates it. Substituting a D-amino acid at position 1 or position 2 prevented that cleavage.

Campbell RM, Stricker P, Miller R, Bongers J, Liu W, Lambros T, Ahmad M, Felix AM, Heimer EP · 1994

Native human GRF is inactivated in three ways: DPP-IV cleavage between residues 2 and 3, chemical rearrangement at Asn8, and oxidation at Met27. Analogues built with substitutions at position 2 (to block DPP-IV), position 8 (to reduce rearrangement), position 15 (Ala15, which improves receptor binding) and position 27 (Leu27, to prevent oxidation) resisted DPP-IV cleavage completely over 24 hours and were 11- to 13-fold more potent than native GRF when injected into pigs.

Jette L, Leger R, Thibaudeau K, Benquet C, Robitaille M, Pellerin I, Paradis V, van Wyk P, Pham K, Bridon DP · 2005

Subcutaneous injection of the unconjugated tetrasubstituted hGRF(1-29) derivatives in rats produced an acute burst of growth hormone in plasma. The albumin-binding version, CJC-1295, was still detectable in plasma beyond 72 hours.

Mayo KE · 1992

The GHRH receptor is a seven-transmembrane G protein-coupled receptor whose messenger RNA is expressed predominantly, if not exclusively, in the anterior pituitary. GHRH binds it with high affinity and stimulates production of intracellular cAMP.

Popovic V, Damjanovic S, Micic D, Djurovic M, Dieguez C, Casanueva FF · 1995

In healthy adults, growth hormone released over 120 minutes measured 484 ug/L per min after GHRH alone and 1435 after GHRP-6 alone, but 3772 when the two were given together. The combined response was significantly greater than the sum of the two given separately.

Raun K, Hansen BS, Johansen NL, Thogersen H, Madsen K, Ankersen M, Andersen PH · 1998

Ipamorelin releases growth hormone through a GHRP-type receptor, which is separate from the GHRH receptor, with potency comparable to GHRP-6. Unlike GHRP-6 and GHRP-2, it did not raise ACTH or cortisol.

Takahashi Y, Kipnis DM, Daughaday WH · 1968

Overnight blood sampling in eight young adults found that in seven of them a large plasma growth hormone peak lasting 1.5 to 3.5 hours began with the onset of deep sleep. Delaying sleep delayed the peak.

Van Cauter E, Copinschi G · 2000

The 24-hour growth hormone profile in healthy young adults consists of stable low levels interrupted by bursts of secretion. The amount of growth hormone secreted is linearly related to the amount of slow-wave sleep, and both decline with age on the same timetable.

Steiger A, Guldner J, Hemmeter U, Rothe B, Wiedemann K, Holsboer F · 1992

Seven healthy men received four intravenous boluses of GHRH across the evening. GHRH raised overnight plasma growth hormone and increased the share of the night spent in slow-wave sleep from 14.0 percent on placebo to 20.2 percent.

Ghigo E, Miola C, Aimaretti G, Valente F, Procopio M, Arvat E, Yin-Zhang W, Camanni F · 1992

In seven healthy adults, an oral glucose load given before GHRH lowered the peak growth hormone response from 11.6 to 7.4 ug/L. The authors attribute the effect to glucose stimulating release of somatostatin, the hormone that opposes GH secretion.

Lanzi R, Manzoni MF, Andreotti AC, Malighetti ME, Bianchi E, Sereni LP, Caumo A, Luzi L, Pontiroli AE · 1997

Six healthy adults received GHRH at three different insulin levels. As insulin rose from 12 to 100 to 194 pmol/L, the growth hormone response to GHRH fell from 4871 to 2414 to 1076 ug/L per 120 min, and insulin level correlated negatively with the GH response. The authors note the insulin levels that reduced the response are the levels normally reached after a meal.

Iranmanesh A, Lizarralde G, Veldhuis JD · 1991

Twenty-four hour blood sampling in 21 healthy men aged 21 to 71 showed that growth hormone production falls about 14 percent with each decade of age, with fewer secretory bursts and a shorter GH half-life in the older men.

Rudman D, Feller AG, Nagraj HS, Gergans GA, Lalitha PY, Goldberg AF, Schlenker RA, Cohn L, Rudman IW, Mattson DE · 1990

Twelve men aged 61 to 81 given growth hormone for six months moved their IGF-1 into the range typical of young adults and gained 8.8 percent in lean body mass while losing 14.4 percent of adipose tissue mass. Skin thickness rose 7.1 percent, which did not reach statistical significance (p = 0.07). An untreated comparison group showed no such changes.

Falutz J, Allas S, Blot K, Potvin D, Kotler D, Somero M, Berger D, Brown S, Richmond G, Fessel J, Turner R, Grinspoon S · 2007

In 412 patients randomly assigned to daily subcutaneous injection of the GHRH analogue tesamorelin or placebo for 26 weeks, visceral adipose tissue fell 15.2 percent on tesamorelin and rose 5.0 percent on placebo, and IGF-1 rose 81 percent. Triglycerides and cholesterol ratios also improved.

Prakash A, Goa KL · 1999

Sermorelin, the unmodified 29-amino-acid GHRH fragment, was well tolerated both as a single intravenous dose and as repeated once-daily subcutaneous doses. Transient facial flushing and pain at the injection site were the most commonly reported adverse events.

Mesa J, Gomez JM, Hernandez C, Pico A, Ulied A · 2003

In a six-month double-blind placebo-controlled trial in 165 adults with growth hormone deficiency, growth hormone significantly increased fat-free mass and decreased fat mass. Scores improved on the energy and emotional-reaction dimensions of the Nottingham Health Profile and on the QoL-AGHDA questionnaire, with no improvement in the placebo group.