Ghrelin administration for chronic respiratory failure: a randomized dose-comparison trial

Repeated ghrelin administration leads to improvements in symptoms, muscle wasting and exercise tolerance in cachectic patients with pulmonary disease. We investigated the optimal ghrelin dose for underweight patients with chronic respiratory failure.

In this multicenter, randomized, dose-comparison exploratory study, 44 cachectic patients with chronic respiratory failure were randomly assigned pulmonary rehabilitation with intravenous twice-daily administration of 1 or 2 μg/kg ghrelin for 3 weeks. The primary endpoint was improvement in 6-min walking distance (6 MWD). The secondary endpoint was change in peak VO2.

Twenty-one patients were assigned to the 1 μg/kg ghrelin group and 23 to the 2 μg/kg ghrelin group. Change from baseline 6 MWD after treatment was similar between groups(1 μg/kg: 53.9 m, 2 μg/kg: 53.9 m, p = 0.99). Mean change in peak VO2 was significantly greater in the 2 μg/kg group (63.1 ml/min) than in the 1 μg/kg group (-63.8 ml/min, p = 0.048). Food intake and lean body mass significantly increased in both groups, and the St. George Respiratory Questionnaire score, body weight, and body mass index were remarkably improved in only the 2 μg/kg group, although there was no significant difference between groups. No treatment-related serious events were reported for either group.

Improvements in the oxygen uptake capacity were greater in patients receiving 2 μg/kg ghrelin twice daily for 3 weeks than in those receiving 1 μg/kg, although exercise tolerance was similar between groups at the end of the 3-week treatment period. Thus, a twice daily dose of 2 μg/kg ghrelin is recommended over 1 μg/kg ghrelin for patients with chronic respiratory failure and weight loss.