Effects of ghrelin treatment on exercise capacity in underweight COPD patients: a substudy of a multicenter, randomized, double-blind, placebo-controlled trial of ghrelin treatment

BMC Pulm Med. 2013 Jun 10;13:37. doi: 10.1186/1471-2466-13-37.


Background: The aim of this substudy of the ghrelin treatment, multicenter, randomized, double-blind, placebo-controlled trial was to investigate the effects of ghrelin administration on exercise capacity and the underlying mechanisms in underweight patients with chronic obstructive pulmonary disease (COPD) using cardiopulmonary exercise testing.

Methods: Twenty underweight COPD patients were randomized to pulmonary rehabilitation with intravenous ghrelin (2 μg/kg, n = 10) or placebo (n = 10) twice daily for 3 weeks in a double-blind fashion. The primary outcome was changes in peak oxygen uptake V•o2. Secondary outcomes included changes in exertional cardio-respiratory functions: O2-pulse, physiologic dead space/tidal volume-ratio (VD/VT), ventilatory equivalent for oxygen V•E/V•o2, and ventilatory equivalent for carbon dioxide V•E/V•co2.

Results: With incremental exercise, at peak exercise, there was a significant difference in the mean difference (ghrelin minus placebo), i.e., treatment effect in: i) peak V•o2 (1.2 mL/kg/min, 95% CI: 0.2-2.3 mL/kg/min, between-group p = 0.025); ii) V•E/V•o2 (-4.2, 95% CI: -7.9 to -0.5, between-group p = 0.030); iii) V•E/V•co2 (-4.1, 95% CI: -8.2 to -0.1, between-group p = 0.045); iv) VD/VT (-0.04, 95% CI: -0.08 to -0.00, between-group p = 0.041); and v) O2-pulse (0.7 mL/beat, 95% CI: 0.3 to 1.2 mL/beat, between-group p = 0.003). Additionally, repeated-measures analysis of variance (ANOVA) indicated a significant time-course effect of ghrelin versus placebo in the peak V•o2 (p = 0.025).

Conclusion: Ghrelin administration was associated with improved exertional capacity and improvements in ventilatory-cardiac parameters.

Trial registration: UMIN (University Hospital Medical Information Network in Japan) C000000061.

Publication types

  • Multicenter Study
  • Randomized Controlled Trial

MeSH terms

  • Administration, Intravenous
  • Aged
  • Double-Blind Method
  • Exercise Test
  • Exercise Tolerance / drug effects*
  • Exercise Tolerance / physiology
  • Female
  • Ghrelin / administration & dosage
  • Ghrelin / pharmacology*
  • Ghrelin / therapeutic use*
  • Humans
  • Male
  • Middle Aged
  • Outcome Assessment, Health Care
  • Pulmonary Disease, Chronic Obstructive / drug therapy*
  • Pulmonary Disease, Chronic Obstructive / physiopathology*
  • Pulmonary Disease, Chronic Obstructive / rehabilitation
  • Respiratory Function Tests
  • Thinness / physiopathology*
  • Treatment Outcome


  • Ghrelin