CJC-1295

Also known as: CJC-1295 DAC, CJC-1295 with DAC, CJC-1295 Drug Affinity Complex

4 notable studies · 5 references

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TLDR

CJC-1295 is a long-acting GHRH analogue that has been shown in controlled human studies to produce sustained increases in endogenous growth hormone and IGF-1 while preserving pulsatile GH secretion, but clinical outcome data and long-term human safety evidence remain limited.

Research Supports

  • Studied for prolonged stimulation of endogenous growth hormone secretion via the GHRH receptor
  • Investigated for downstream effects on IGF-1 signaling after GH stimulation
  • Studied for whether sustained GHRH stimulation preserves normal pulsatile GH release
  • Evaluated by FDA for potential compounding use in growth hormone deficiency
  • Studied as an example of albumin-binding technology for extending peptide half-life

Observations Reported in Research

  • Single dose produced GH increases of roughly 2- to 10-fold lasting six days or longer (Teichman et al., 2006)
  • IGF-1 rose about 1.5- to 3-fold and stayed elevated 9-11 days after a single dose (Teichman et al., 2006)
  • Repeated dosing kept IGF-1 above baseline for up to 28 days (Teichman et al., 2006)
  • Overnight sampling showed GH secretion stayed pulsatile despite continuous stimulation (Frohman et al., 2006)
  • In rats, CJC-1295 produced about a fourfold increase in GH area-under-the-curve versus hGRF(1-29) (Jette et al., 2005)

These are brief summaries of what the referenced research examined or reported — not conclusions about safety or effectiveness, and not medical advice. See Notable Studies and Sources & References below for the full context and citations.

At a Glance

Classification: Synthetic growth hormone-releasing hormone (GHRH/GRF) analogue; long-acting growth hormone secretagogue

CJC-1295 is a synthetic analogue of growth hormone-releasing hormone designed to produce prolonged stimulation of endogenous growth hormone secretion. The best-characterized form contains a Drug Affinity Complex (DAC) that enables the peptide to bind covalently to circulating serum albumin. This dramatically extends its biological exposure compared with native GHRH. In randomized human studies, CJC-1295 produced sustained increases in growth hormone and IGF-1 lasting days after a single administration. Researchers reported an estimated half-life of approximately 5.8–8.1 days. However, clinical development remained limited. CJC-1295 is not FDA-approved, long-term human safety has not been established, and FDA has identified safety and product-characterization concerns involving CJC-1295-related substances.

What Is CJC-1295?

CJC-1295 was developed as a longer-lasting analogue of the biologically active 1–29 portion of human growth hormone-releasing hormone. Native GHRH has a very short circulating half-life, which limits prolonged pharmacological stimulation. Researchers modified the peptide to improve resistance to enzymatic degradation and added a reactive Drug Affinity Complex, or DAC. After administration, the DAC can form a covalent bond with serum albumin. This effectively uses albumin as a circulating carrier for the peptide, greatly extending its duration in the bloodstream. Preclinical experiments demonstrated that CJC-1295 could associate with albumin and remain detectable considerably longer than ordinary GRF(1-29). Human studies subsequently demonstrated prolonged increases in both GH and IGF-1.

What Are Researchers Studying?

Growth hormone secretion

The primary research purpose of CJC-1295 has been prolonged stimulation of endogenous growth hormone secretion. Human studies demonstrated dose-dependent increases in average GH concentrations lasting six days or longer after a single administration. Unlike direct administration of recombinant growth hormone, CJC-1295 stimulates the pituitary through the GHRH receptor.

IGF-1 signaling

Growth hormone stimulates production of insulin-like growth factor 1, particularly in the liver. Human CJC-1295 research demonstrated increases in circulating IGF-1 lasting substantially longer than the initial administration. After a single exposure, average IGF-1 concentrations increased approximately 1.5- to 3-fold and remained elevated for roughly 9–11 days in the original clinical study. With repeated administration, elevated IGF-1 levels persisted for considerably longer.

Growth hormone pulsatility

An important question was whether long-lasting GHRH stimulation would flatten normal pulsatile GH secretion. Researchers therefore performed intensive overnight blood sampling before and after CJC-1295 administration. The study found that pulsatile GH secretion persisted despite continuous stimulation from the long-acting compound. CJC-1295 increased GH secretion while preserving the physiological pulsatile pattern rather than simply creating constant GH exposure.

Growth hormone deficiency

The pharmacological rationale behind CJC-1295 led to interest in its potential use for growth hormone deficiency. FDA evaluated CJC-1295-related substances specifically in connection with proposed compounding for growth hormone deficiency. However, the available clinical development did not establish CJC-1295 as an approved treatment for growth hormone deficiency, and FDA concluded that the available information weighed against adding the evaluated CJC-1295 substances to the 503A Bulks List.

Albumin-binding peptide technology

CJC-1295 is also scientifically interesting as an example of extending peptide exposure through in-vivo albumin conjugation. The DAC modification contains a reactive maleimide group designed to form a covalent bond with albumin. Early animal experiments confirmed formation of an albumin-associated CJC-1295 species and demonstrated substantially prolonged circulation compared with native GRF(1-29). This approach illustrates one strategy researchers have explored for overcoming the characteristically short half-lives of peptide hormones.

How Does It Work?

CJC-1295 acts primarily as an agonist of the growth hormone-releasing hormone receptor. GHRH receptors are expressed on somatotroph cells of the anterior pituitary. Activation stimulates synthesis and release of growth hormone. Growth hormone subsequently stimulates production of IGF-1 and affects numerous downstream physiological systems involving: • Growth signaling • Protein metabolism • Lipid metabolism • Glucose regulation • Body composition • Tissue growth and repair The defining pharmacological feature of CJC-1295 DAC is not merely GHRH receptor activation—it is its prolonged exposure. The DAC modification allows CJC-1295 to bind serum albumin after administration. Albumin circulates for much longer than an ordinary small peptide, allowing the attached CJC-1295 molecule to remain available for extended periods. Preclinical experiments found CJC-1295-associated albumin in circulation more than 24 hours after administration and detectable peptide beyond 72 hours. Human pharmacokinetic studies subsequently estimated a half-life of approximately 5.8–8.1 days.

What Does the Research Show?

Human research

Unlike many research peptides, CJC-1295 has direct randomized human evidence. Two randomized, double-blind, placebo-controlled dose-escalation studies investigated healthy adults aged 21–61. After a single administration, average plasma GH concentrations increased approximately 2- to 10-fold for six days or longer. Average IGF-1 concentrations increased approximately 1.5- to 3-fold for 9–11 days. Researchers estimated the compound's half-life at 5.8–8.1 days. Following repeated administration, average IGF-1 concentrations remained above baseline for as long as 28 days. A second analysis investigated GH pulsatility in healthy men using blood sampling every 20 minutes overnight. CJC-1295 increased GH secretion while preserving pulsatile release. These studies demonstrate biological activity in humans. They do not establish long-term clinical efficacy or safety for growth hormone deficiency, body composition, recovery, anti-aging, or other uses frequently associated with CJC-1295 online. FDA's later review emphasized that the available clinical data remain limited.

Animal research

Animal research played an important role in the development of CJC-1295. Researchers initially tested modified GRF(1-29) peptides capable of forming albumin bioconjugates. In rats, the compounds remained biologically active after albumin association and stimulated growth hormone secretion. CJC-1295 produced approximately a fourfold increase in GH area-under-the-curve compared with ordinary hGRF(1-29) during an early experiment and remained detectable in plasma beyond 72 hours. These studies established the albumin-binding concept that subsequently led to human trials.

In-vitro research

Early laboratory studies evaluated CJC-1295-related molecules using cultured pituitary cells and biochemical characterization. Albumin-conjugated GRF analogues retained the ability to stimulate GH secretion from cultured rat anterior pituitary cells. These experiments helped demonstrate that attachment to albumin did not eliminate the peptide's biological activity. Laboratory studies also contributed to characterization of peptide stability and albumin binding.

Notable Studies

Human Growth Hormone-Releasing Factor (hGRF)1-29-Albumin Bioconjugates Activate the GRF Receptor on the Anterior Pituitary in Rats: Identification of CJC-1295 as a Long-Lasting GRF Analog

animal

Jette J. J. et al. · 2005

Researchers engineered modified hGRF(1-29) molecules capable of forming albumin bioconjugates. The molecules remained biologically active in cultured pituitary cells. In rats, CJC-1295 produced substantially greater GH exposure than ordinary hGRF(1-29 and was detectable in circulation beyond 72 hours. Researchers also demonstrated formation of an albumin-associated CJC-1295 species in vivo.

Limitations: The experiments primarily involved rats and cultured rat pituitary cells. They established mechanism and pharmacological plausibility but could not establish human clinical efficacy or long-term safety.

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Prolonged Stimulation of Growth Hormone (GH) and Insulin-Like Growth Factor I Secretion by CJC-1295, a Long-Acting Analog of GH-Releasing Hormone, in Healthy Adults

human

Sam L. Teichman, Ann Neale, Betty Lawrence, Catherine Gagnon, Jean-Paul Castaigne, and Lawrence A. Frohman · 2006

Researchers conducted two randomized controlled studies lasting 28 and 49 days in healthy adults. A single administration produced dose-dependent increases in average GH concentrations of approximately 2- to 10-fold for at least six days. Average IGF-1 concentrations increased approximately 1.5- to 3-fold for 9–11 days. The estimated half-life was approximately 5.8–8.1 days. Repeated administration produced a cumulative effect, with elevated IGF-1 concentrations persisting for as long as 28 days.

Limitations: Participants were healthy adults rather than patients with growth hormone deficiency. The studies were short and primarily investigated pharmacokinetics and pharmacodynamics. They were not designed to establish long-term clinical benefits or detect uncommon adverse events.

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Pulsatile Secretion of Growth Hormone (GH) Persists During Continuous Stimulation by CJC-1295, a Long-Acting GH-Releasing Hormone Analog

human

Lawrence A. Frohman, et al. · 2006

Researchers studied healthy men before and one week after CJC-1295 administration. Blood was sampled every 20 minutes during a 12-hour overnight period to characterize growth hormone secretion. Despite the prolonged pharmacological action of CJC-1295, GH secretion remained pulsatile. The findings suggested that continuous GHRH-receptor stimulation could increase overall GH secretion without eliminating the physiological pattern of GH pulses.

Limitations: The study involved a small number of healthy men and investigated endocrine physiology rather than clinical outcomes. It did not establish benefits involving body composition, recovery, growth hormone deficiency, aging, or other proposed applications.

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FDA Evaluation of CJC-1295-Related Bulk Drug Substances for the 503A Bulks List

animal

U.S. Food and Drug Administration · 2024

FDA evaluated several CJC-1295-related substances, including forms with and without DAC, proposed for compounding in growth hormone deficiency. FDA found important uncertainties involving nomenclature, identity, characterization, impurities, aggregation, immunogenicity, and the limited clinical evidence. The agency also identified reported adverse effects including increased heart rate and systemic vasodilatory reactions and concluded that the available evidence weighed against placing the evaluated substances on the 503A Bulks List.

Limitations: This was a regulatory evaluation rather than a clinical trial. Its purpose was to assess suitability for pharmacy compounding, not determine whether CJC-1295 has biological activity.

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What We Still Don't Know

Major unanswered questions include: • Long-term safety in humans • Clinical effectiveness in growth hormone deficiency • Whether sustained GH/IGF-1 increases produce meaningful improvements in patient outcomes • Long-term metabolic effects • Long-term consequences of sustained IGF-1 elevation • Immunogenicity after prolonged repeated exposure • Safety in pediatric populations • Effects in older adults • Whether benefits proposed for body composition, recovery, or aging occur in controlled human trials • How different CJC-1295-related chemical forms compare pharmacologically • Whether products labeled “CJC-1295” outside formal clinical research actually contain the same molecule investigated in published trials FDA has specifically emphasized that long-term repeated-exposure data are lacking and that available clinical information does not adequately characterize long-term safety.

Related Compounds

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Sources & References

  1. 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-1295, a Long-Acting Analog of GH-Releasing Hormone, in Healthy Adults. Journal of Clinical Endocrinology & Metabolism. 2006;91(3):799–805. doi:10.1210/jc.2005-1536.
  2. Frohman LA, et al. Pulsatile Secretion of Growth Hormone (GH) Persists During Continuous Stimulation by CJC-1295, a Long-Acting GH-Releasing Hormone Analog. Journal of Clinical Endocrinology & Metabolism. 2006.
  3. U.S. Food and Drug Administration. Pharmacy Compounding Advisory Committee: CJC-1295-Related Bulk Drug Substances. December 4, 2024.
  4. U.S. Food and Drug Administration. Certain Bulk Drug Substances for Use in Compounding That May Present Significant Safety Risks. CJC-1295.
  5. Jette L, et al. Human Growth Hormone-Releasing Factor (hGRF)1-29-Albumin Bioconjugates Activate the GRF Receptor on the Anterior Pituitary in Rats: Identification of CJC-1295 as a Long-Lasting GRF Analog. Endocrinology. 2005.

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