These endocrine effects were associated with a significant increase in Fat Free Mass (FFM), and concomitant reduction in Fat Mass (FM) when measured by DEXA scan and bioelectrical impedance (BIA). Total body protein turnover, as measured by 13C leucine kinetics, was normal in both treatment groups already at baseline, most probably reflecting adaptative changes of metabolic balance in the chronic disease state.
The study conducted at three European sites was designed to evaluate the clinical potential of GHRH analog (AKL-0707) administration in improving body composition, nutritional and metabolic parameters in malnourished patients with stage IV or pre-dialytic stage V chronic kidney disease.
A 393% increase in mean 24-hour integrated GH secretion rate as compared to a 22% increase in the placebo group (24h AUC) was observed. GHRH analog treatment did not affect the natural pulsatile rhythm of endogenous GH secretion. A 104% increase in median total circulating IGF-1, mean 26.7% decrease in IGFBP-1 and no significant change in IGFBP3 concentration, indicating an increase in the free circulating IGF-1 available to tissues, as compared to 3.5% increase in IGF-1 and 2.4% increase in IGFBP concentrations in the placebo group. In the GHRH group, six out of nine patients rated malnourished at baseline were classified well-nourished after four weeks of therapy.
By contrast, the nutritional assessment remained unchanged in each of 11 patients classified malnourished in the placebo group. An increase from baseline in FFM (median 3.3kg by BIA and 1.6kg by DEXA) and a concomitant decrease in FM (median 1.8kg by BIA and 0.4kg by DEXA) was also noticed. These changes were observed in all but one (11/12) patients in the GHRH analog group on day 28, and contrasted with a decrease in FFM and an increase in FM in the placebo arm. The increase in FFM was most pronounced in the leg and trunk regions.
Halvor Jaeger, CEO of Akela Pharma, said: “The positive final results of our GHRH Phase II clinical trial confirm the substantial therapeutic potential of GHRH analog, and clearly justify pursuing further clinical studies in not only chronic renal failure but also in other wasting diseases such as severe COPD and HIV-infection associated wasting.”