Randomized, dose-finding trial of ghrelin treatment for chronic respiratory failure

ObjectivesGhrelin, a growth hormone-releasing peptide, has shown efficacy in chronic obstructive pulmonary disease (COPD) patients in previous trials. This study was designed to evaluate the effective dose of ghrelin in chronic respiratory failure patients. MethodsIn this randomized, double-blind, dose-finding, single-center study, 18 patients, including 16 with COPD, were randomly assigned to receive pulmonary rehabilitation (PR) with intravenous ghrelin at 1 g/kg or 2 g/kg, twice daily for 3 weeks. The primary outcome was the change in peak oxygen uptake ( Vo2). Secondary outcomes included changes in plasma vascular endothelial growth factor (VEGF)-A levels, and exertional cardio-respiratory functions with blood gas analysis. ResultsWith incremental exercise, there was no significant differences in the mean difference (high-dose ghrelin minus low-dose ghrelin) of peak Vo2 (1.0 mL/kg/min, 95% CI: -0.6 to 2.6 mL/kg/min, between-group, P=0.193). However, there were significant differences in the mean difference of (i) O-2-pulse (0.6 mL/beats, 95% CI: 0.0 to 1.1 mL/beats, between-group, P=0.035) at iso-time; and ii) PaO2 (4.2 mmHg, 95% CI: 0.2 to 8.2 mmHg, between-group, P=0.041) and PaCO2 (-3.1 mmHg, 95% CI: -6.0 to -0.3 mmHg, between-group, P=0.034) at peak exercise. The mean difference in the plasma VEGF-A level was significantly inhibited by high dose-ghrelin with PR (-125.4 pg/mL, 95% CI: -235.2 to -15.5 pg/mL, between-group, P=0.028). ConclusionAlthough the primary outcome of the study was not met, high-dose ghrelin with PR improved exertional cardiac function and blood gas values, and inhibited circulating VEGF-A levels.