title: Ghrelin treatment of cachectic patients with chronic obstructive pulmonary disease: a multicenter, randomized, double-blind, placebo-controlled trial.
abstract: 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.
  
  
  RESULTS
  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
  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.
  
  
  BACKGROUND
  UMIN Clinical Trial Registry C000000061.
authors.affiliation: Department of Internal Medicine, National Hospital Organization Toneyama National Hospital, Toyonaka, Japan. mikisuke@toneyama.go.jp
authors.forename: Keisuke
authors.initials: K
authors.lastname: Miki
authors.forename: Ryoji
authors.initials: R
authors.lastname: Maekura
authors.forename: Noritoshi
authors.initials: N
authors.lastname: Nagaya
authors.forename: Masamitsu
authors.initials: M
authors.lastname: Nakazato
authors.forename: Hiroshi
authors.initials: H
authors.lastname: Kimura
authors.forename: Shinsuke
authors.initials: S
authors.lastname: Murakami
authors.forename: Shunsuke
authors.initials: S
authors.lastname: Ohnishi
authors.forename: Toru
authors.initials: T
authors.lastname: Hiraga
authors.forename: Mari
authors.initials: M
authors.lastname: Miki
authors.forename: Seigo
authors.initials: S
authors.lastname: Kitada
authors.forename: Kenji
authors.initials: K
authors.lastname: Yoshimura
authors.forename: Yoshitaka
authors.initials: Y
authors.lastname: Tateishi
authors.forename: Yasuji
authors.initials: Y
authors.lastname: Arimura
authors.forename: Nobuhiro
authors.initials: N
authors.lastname: Matsumoto
authors.forename: Masanori
authors.initials: M
authors.lastname: Yoshikawa
authors.forename: Kenichi
authors.initials: K
authors.lastname: Yamahara
authors.forename: Kenji
authors.initials: K
authors.lastname: Kangawa
mesh_terms: D000368:Aged; D000369:Aged, 80 and over; D002100:Cachexia / Q000150:complications / Q000188:drug therapy* / Q000534:rehabilitation; D003131:Combined Modality Therapy; D003863:Depression / Q000139:chemically induced; D004311:Double-Blind Method; D004334:Drug Administration Schedule; D005260:Female; D054439:Ghrelin / Q000009:adverse effects / Q000097:blood / Q000627:therapeutic use*; D006801:Humans; D008297:Male; D008875:Middle Aged; D011014:Pneumonia / Q000139:chemically induced; D029424:Pulmonary Disease, Chronic Obstructive / Q000150:complications*; D011788:Quality of Life; D012129:Respiratory Function Tests; D011795:Surveys and Questionnaires; D013997:Time Factors; D016896:Treatment Outcome; D016138:Walking
chemical_list: D054439:Ghrelin