Randomized, dose‐finding trial of ghrelin treatment for chronic respiratory failure. (10th September 2015)

• Record Type: Journal Article
• Authors: Miki, Keisuke; Maekura, Ryoji; Nakazato, Masamitsu; Matsumoto, Nobuhiro; Kitada, Seigo; Miki, Mari; Yoshimura, Kenji; Mori, Masahide; Kangawa, Kenji
• Is Part Of: Clinical respiratory journal. Volume 11:Number 4(2017)
• Page Start: 496
• Page End: 505
• Publication Date: 2015-09-10
• Subjects: chronic obstructive pulmonary disease – dyspnea – exercise – pulmonary rehabilitation – vascular endothelial growth factor; Respiratory organs -- Diseases -- Periodicals; Respiratory organs -- Periodicals; 616.24
• DOI: 10.1111/crj.12364
• Languages: English
• ISSNs: 1752-6981

Abstract

Abstract: Objectives: Ghrelin, 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. Methods: In 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 μg/kg or 2 μg/kg, twice daily for 3 weeks. The primary outcome was the change in peak oxygen uptake ( V ˙ o 2 ). Secondary outcomes included changes in plasma vascular endothelial growth factor (VEGF)‐A levels, and exertional cardio‐respiratory functions with blood gas analysis. Results: With incremental exercise, there was no significant differences in the mean difference (high‐dose ghrelin minus low‐dose ghrelin) of peak V ˙ o 2 (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) O2 ‐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). Conclusion: Although 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.