Growth hormone - ibutamoren

The growth hormone somatropin is made in the pituitary gland, and a variety of conditions can result if its secretion is faulty.

It is secreted in a pulsatile manner, controlled by growth hormone releasing hormone (GHRH) and somastatin. The former, released by the hypothalamus, stimulates the synthesis and release of somatropin, while the peptide somastatin, which is found in the mucosal endocrine cells in the gastrointestinal tract, inhibits its release. Other endogenous substances are also believed to be involved in its secretion.

Synthetic growth hormone secretagogues (GHSs) can stimulate the release of somatropin, and it is thought that these may even be better than recombinant somatropin at inducing pulsatile growth hormone secretion. Ibutamoren is being investigated by Merck as a potential GHS, and a large number of trials have been carried out.¹

In a randomised placebo controlled crossover Phase I study, eight healthy subjects who had undergone diet-induced caloric restriction were given 25mg ibutamoren orally once a day to investigate its effects on diet-induced nitrogen wasting.² The drug was generally well tolerated, and it significantly improved overall nitrogen balance, showing that it may be of use in treating catabolic disorders.

A group of 65 healthy elderly subjects, both male and female, were given the drug in a two-year double blind, placebo-controlled crossover trial.³ It significantly increased mean growth hormone levels, and to a greater extent in men and those women who were receiving hormone replacement therapy. Once the subjects crossed over to placebo treatment, the mean levels returned to baseline.

In another randomised, double blind, placebo-controlled trial, healthy elderly subjects were given 2, 10 or 25mg ibutamoren once a day for up to four weeks.⁴ After two weeks of treatment, serum growth hormone levels rose dose dependently, and growth hormone pulse height increased significantly, though the number of pulses did not change.

A further trial in both elderly and younger patients with no sleep disorders looked at its effect on sleep quality.⁵ Eight patients aged between 18 and 30, and six aged 65-71, were given 5 and 25mg doses in a double blind, placebo-controlled trial. The duration of stage IV sleep and REM sleep increased significantly in the younger subjects; older ones had significant increases in REM sleep and REM latency, and significant decreases in deviations from normal sleep.

It has also been investigated in adults with severe growth hormone deficiency. In a double blind, escalating dose study in nine patients who had received growth hormone treatment in childhood, subjects were given 10 or 50mg doses of ibutamoren once a day for two four-day periods, at least 28 days apart.⁶ It gave significant increases in growth hormone levels, and was most effective at inducing responses in those who initially had a greater deficiency.

Numerous other trials have been carried out, and it is currently being looked at as a potential treatment for sarcopenia in patients with hip fractures, primary fibromyalgia and Alzheimer's disease.