title: Randomized, dose-finding trial of ghrelin treatment for chronic respiratory failure.
abstract: OBJECTIVE
  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˙o2). 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˙o2 (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).
  
  
  CONCLUSIONS
  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.
authors.affiliation: Department of Respiratory Medicine, National Hospital Organization Toneyama National Hospital, Toyonaka, Japan.
authors.forename: Keisuke
authors.initials: K
authors.lastname: Miki
authors.affiliation: Department of Respiratory Medicine, National Hospital Organization Toneyama National Hospital, Toyonaka, Japan.
authors.forename: Ryoji
authors.initials: R
authors.lastname: Maekura
authors.affiliation: Neurology, Respirology, Endocrinology and Metabolism, Internal Medicine, Faculty of Medicine, University of Miyazaki, Miyazaki, Japan.
authors.forename: Masamitsu
authors.initials: M
authors.lastname: Nakazato
authors.affiliation: Neurology, Respirology, Endocrinology and Metabolism, Internal Medicine, Faculty of Medicine, University of Miyazaki, Miyazaki, Japan.
authors.forename: Nobuhiro
authors.initials: N
authors.lastname: Matsumoto
authors.affiliation: Department of Respiratory Medicine, National Hospital Organization Toneyama National Hospital, Toyonaka, Japan.
authors.forename: Seigo
authors.initials: S
authors.lastname: Kitada
authors.affiliation: Department of Respiratory Medicine, National Hospital Organization Toneyama National Hospital, Toyonaka, Japan.
authors.forename: Mari
authors.initials: M
authors.lastname: Miki
authors.affiliation: Department of Respiratory Medicine, National Hospital Organization Toneyama National Hospital, Toyonaka, Japan.
authors.forename: Kenji
authors.initials: K
authors.lastname: Yoshimura
authors.affiliation: Department of Respiratory Medicine, National Hospital Organization Toneyama National Hospital, Toyonaka, Japan.
authors.forename: Masahide
authors.initials: M
authors.lastname: Mori
authors.affiliation: Department of Biochemistry, National Cerebral and Cardiovascular Center Research Institute, Suita, Japan.
authors.forename: Kenji
authors.initials: K
authors.lastname: Kangawa
mesh_terms: D061605:Administration, Intravenous; D000368:Aged; D001784:Blood Gas Analysis; D005081:Exercise Therapy / Q000379:methods; D017079:Exercise Tolerance / Q000187:drug effects; D005260:Female; D054439:Ghrelin / Q000008:administration & dosage / Q000627:therapeutic use*; D006801:Humans; D008297:Male; D008875:Middle Aged; D009842:Oligopeptides / Q000008:administration & dosage / Q000627:therapeutic use*; D017063:Outcome Assessment, Health Care; D010101:Oxygen Consumption / Q000187:drug effects; D029424:Pulmonary Disease, Chronic Obstructive / Q000188:drug therapy* / Q000503:physiopathology / Q000534:rehabilitation; D012129:Respiratory Function Tests / Q000379:methods; D042461:Vascular Endothelial Growth Factor A / Q000097:blood* / Q000187:drug effects
chemical_list: D054439:Ghrelin; D009842:Oligopeptides; D042461:Vascular Endothelial Growth Factor A; C420120:gamma-aminobutyryl-2-methyltryptophyl-2-methyltryptophyl-2-methyltryptophyl-lysinamide
keywords: chronic obstructive pulmonary disease - dyspnea - exercise - pulmonary rehabilitation - vascular endothelial growth factor