1999
Sermorelin is the shortest lab-made piece of growth hormone-releasing hormone (GHRH) with full activity. A single intravenous (into a vein) 1 mcg/kg dose is a quick and fairly specific test for growth hormone deficiency, giving fewer false positives in children without the deficiency than other stimulation tests. A normal response cannot rule out a hypothalamic cause (a problem in the brain's hormone control center), so it is used alongside standard testing, not instead of it. For treatment, the review calls the data limited: once-daily 30 mcg/kg injected under the skin at bedtime raised height velocity (growth speed) over 12 months in some prepubertal children with idiopathic deficiency (deficiency with no known cause), with a few children followed to 36 months, and the effect on final adult height was never determined. Height-velocity gains were SMALLER than those in children given somatropin (lab-made growth hormone) at the same 30 mcg/kg per day. Across that program, 350 patients were given sermorelin in clinical trials, and transient (short-lived) facial flushing and injection-site pain were the most commonly reported side effects.
Prakash A, Goa KL
1993
In a study of 30 healthy men, even tiny intravenous doses (into a vein) of just 0.25 micrograms per kilogram of body weight produced significant growth hormone release. The maximum growth hormone response occurred at doses of 1-2 micrograms per kilogram, with peak growth hormone levels reaching approximately 90 milli-international units per liter. Growth hormone levels stayed high for about 3 hours even though the peptide itself was cleared quickly from the body. Intranasal delivery (through the nose) had poor bioavailability (the share that reaches the blood) of only 3-5%, but higher intranasal doses of 50 micrograms per kilogram were as effective as just 1 microgram per kilogram given intravenously. Importantly, repeated intranasal dosing did not suppress the body's natural nighttime growth hormone release.
Wilton P, et al
2000
Testing with low-dose GHRH(1-29) revealed that patients with growth hormone deficiency caused by radiation therapy showed a reduced growth hormone response compared to healthy individuals. This demonstrated that GHRH(1-29) is a useful diagnostic tool for identifying and characterizing different types of growth hormone deficiency.
Achermann JC, et al
1999
Studies using continuous GHRH(1-29) infusions showed how growth hormone pulses are actually produced in the body. Growth hormone pulses come from the on-and-off withdrawal of somatostatin (a hormone that holds growth hormone down), while GHRH(1-29) provides a steady background signal that allows growth hormone release. This mechanism explains why GHRH(1-29) is so effective at stimulating natural growth hormone release.
Achermann JC, et al
1996
The trial the approved dose comes from. 110 previously untreated prepubertal (before puberty) children with growth hormone deficiency received 30 mcg/kg per day of GHRH(1-29) under the skin at bedtime for up to a year in a multicentre open-label study (many sites; everyone knew they were getting the drug); 86 were eligible for the efficacy analysis. Mean height velocity (growth speed) rose from 4.1 ± 0.9 cm/year at baseline to 8.0 ± 1.5 cm/year at 6 months and 7.2 ± 1.3 cm/year at 12 months, and 74% of the children were judged good responders at 6 months. Bone age advanced in step with height age (ratio 1.04 ± 0.58, p=0.63), fasting glucose (blood sugar) did not change, and there was no excessive IGF-I generation (IGF-I is a growth signal made in response to growth hormone). Open-label: there was no placebo arm.
Thorner M, Rochiccioli P, Colle M, Lanes R, Grunt J, Galazka A, Landy H, Eengrand P, Shah S
1997
Nine prepubertal children with growth hormone deficiency caused by cranial or craniospinal irradiation (radiation to the head or to the head and spine) received GHRH(1-29)-NH2 15 mcg/kg TWICE daily by injection under the skin for a year, a divided dose, 30 mcg/kg across the day. Height velocity (growth speed) rose from 3.3 cm/year before treatment to 6.0 cm/year (p=0.004). In the following year on growth hormone itself the same children grew 7.5 cm/year, so GHRH worked but worked less well than GH. In that group (n=9), with no control arm and no placebo, no side effects attributable to GHRH and no harmful changes in clinical chemistry, haematology (blood counts), lipids (blood fats) or thyroid function were recorded over the treatment year. The group was far too small to detect anything uncommon.
Ogilvy-Stuart AL, Stirling HF, Kelnar CJ, Savage MO, Dunger DB, Buckler JM, Shalet SM
1997
The adult trial, and it tested a different molecule. Ten women and nine men aged 55 to 71 injected themselves with saline every night for 4 weeks, then [Nle27]GHRH-(1-29)-NH2 (a norleucine-27 analogue, a modified version, not sermorelin) at 10 mcg/kg every night for 16 weeks, single-blind (participants did not know what they got) and placebo-controlled. Nocturnal GH (night-time growth hormone) rose in both sexes (women p<0.01, men p<0.05) and IGF-I rose within 2 weeks (p<0.05) but drifted back toward baseline by 16 weeks. Skin thickness increased in both sexes (p<0.05). Lean body mass (non-fat tissue) increased in MEN ONLY (p<0.05), with no other change in body composition and no change in bone mineral density (bone strength) in either sex; body fat did not fall. Insulin sensitivity, general well-being (p<0.05) and libido (sex drive) (p<0.01) improved in men only. Sleep quality was unaffected. The only side effect was transient hyperlipidaemia (short-lived high blood fats), resolved by the end of the study. Nineteen people.
Khorram O, Laughlin GA, Yen SS
1997
The same 19 people and the same norleucine-27 analogue at 10 mcg/kg every night for 16 weeks. Twelve-hour integrated GH (total growth hormone over 12 hours) rose 107% in men and 70% in women, and IGF-I rose 28%. B cells (antibody-making immune cells) rose 30% by 16 weeks with a 50% increase in responsiveness to B-cell mitogens (substances that trigger B cells to multiply), lymphocytes expressing the IL-2 receptor (activated immune cells) rose 70%, and T-cell responsiveness to phytohaemagglutinin (a plant substance used to test T cells) rose 50%. Total T cells, T-cell subsets and natural killer cells did not change. The authors report no side effects. Again: 19 people, an analogue rather than sermorelin, and immune cell counts rather than any clinical outcome such as infection rate.
Khorram O, Yeung M, Vu L, Yen SS