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Diabetes and Endocrinology - Geriatrics - Pharmacology - Respiratory Medicine


Ghrelin Treatment of Cachectic Patients with Chronic Obstructive Pulmonary Disease: A Multicenter, Randomized, Double-Blind, Placebo-Controlled Trial
Published: Tuesday, May 01, 2012
Author: Keisuke Miki et al.

by Keisuke Miki, Ryoji Maekura, Noritoshi Nagaya, Masamitsu Nakazato, Hiroshi Kimura, Shinsuke Murakami, Shunsuke Ohnishi, Toru Hiraga, Mari Miki, Seigo Kitada, Kenji Yoshimura, Yoshitaka Tateishi, Yasuji Arimura, Nobuhiro Matsumoto, Masanori Yoshikawa, Kenichi Yamahara, Kenji Kangawa

Background

Pulmonary cachexia is common in advanced chronic obstructive pulmonary disease (COPD), culminating in exercise intolerance and a poor prognosis. Ghrelin is a novel growth hormone (GH)-releasing peptide with GH-independent effects. The efficacy and safety of adding ghrelin to pulmonary rehabilitation (PR) in cachectic COPD patients were investigated.

Methodology/Principal Findings

In a multicenter, randomized, double-blind, placebo-controlled trial, 33 cachectic COPD patients were randomly assigned PR with intravenous ghrelin (2 µg/kg) or placebo twice daily for 3 weeks in hospital. The primary outcomes were changes in 6-min walk distance (6-MWD) and the St. George Respiratory Questionnaire (SGRQ) score. Secondary outcomes included changes in the Medical Research Council (MRC) scale, and respiratory muscle strength. At pre-treatment, serum GH levels were increased from baseline levels by a single dose of ghrelin (mean change, +46.5 ng/ml; between-group p<0.0001), the effect of which continued during the 3-week treatment. In the ghrelin group, the mean change from pre-treatment in 6-MWD was improved at Week 3 (+40 m, within-group p?=?0.033) and was maintained at Week 7 (+47 m, within-group p?=?0.017), although the difference between ghrelin and placebo was not significant. At Week 7, the mean changes in SGRQ symptoms (between-group p?=?0.026), in MRC (between-group p?=?0.030), and in maximal expiratory pressure (MEP; between-group p?=?0.015) were better in the ghrelin group than in the placebo group. Additionally, repeated-measures analysis of variance (ANOVA) indicated significant time course effects of ghrelin versus placebo in SGRQ symptoms (p?=?0.049) and MEP (p?=?0.021). Ghrelin treatment was well tolerated.

Conclusions/Significance

In cachectic COPD patients, with the safety profile, ghrelin administration provided improvements in symptoms and respiratory strength, despite the lack of a significant between-group difference in 6-MWD.

Trial Registration

UMIN Clinical Trial Registry C000000061

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