PLoS ONE (Jan 2012)

Ghrelin treatment of cachectic patients with chronic obstructive pulmonary disease: a multicenter, randomized, double-blind, placebo-controlled trial.

  • 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

DOI
https://doi.org/10.1371/journal.pone.0035708
Journal volume & issue
Vol. 7, no. 5
p. e35708

Abstract

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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.