Open AccessRandomized, dose‐finding trial of ghrelin treatment for chronic respiratory failure
Author(s) -
Miki Keisuke,
Maekura Ryoji,
Nakazato Masamitsu,
Matsumoto Nobuhiro,
Kitada Seigo,
Miki Mari,
Yoshimura Kenji,
Mori Masahide,
Kangawa Kenji
Publication year - 2017
Publication title -
the clinical respiratory journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.789
H-Index - 33
eISSN - 1752-699X
pISSN - 1752-6981
DOI - 10.1111/crj.12364
Subject(s) - medicine , randomized controlled trial , ghrelin , intensive care medicine , hormone
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 peakV ˙ 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) 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) PaO 2 (4.2 mmHg, 95% CI: 0.2 to 8.2 mmHg, between‐group, P = 0.041) and PaCO 2 (−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.