Effects of ghrelin receptor agonist, relamorelin, on gastric motor functions and satiation in healthy volunteers

Abstract

Background: Synthetic human ghrelin accelerates gastric emptying, reduces gastric accommodation, and results in numerical increases in postprandial symptom scores. The ghrelin receptor agonist, relamorelin, accelerates gastric emptying in patients with diabetic gastroparesis.

Aim: To measure pharmacological effects of relamorelin on gastric accommodation, distal antral motility, and satiation in healthy volunteers.

Methods: In a placebo-controlled, double-blind, randomized study of 16 healthy volunteers, we compared effects of 30 μg subcutaneous (s.c.) relamorelin to placebo on: (i) gastric volumes measured by single photon emission computed tomography, (ii) 1-h postprandial distal antral motility index (MI) by 15-lumen perfusion gastroduodenal manometry, and (iii) satiation tested by Ensure nutrient drink test. Primary endpoints were: fasting and postprandial gastric volumes, distal antral phasic pressure activity (number of contractions, mean amplitude, and MI), and maximum tolerated volume. Results were normally distributed and the two treatment groups were compared using t-test.

Key results: Relamorelin, 30 μg s.c., significantly increased the number of contractions in the distal antrum during 0-60 min postmeal when compared to placebo (p = 0.022); this was also observed in the first two 15-min periods (p = 0.005 and 0.015 for number of contractions 0-15 and 16-30). There was borderline increase in MI0-15 (p = 0.055) and numerically increased MI0-60 (p = 0.139) and MI16-30 (p = 0.116). The amplitude of contractions was not significantly increased. Relamorelin did not significantly alter fasting or postprandial gastric volumes, gastric accommodation, or satiation volumes and symptoms.

Conclusions & inferences: Relamorelin increases frequency of distal antral motility contractions without significant effects on amplitude of contractions. The lack of inhibition of accommodation and absence of increase in satiation symptoms support relamorelin for the treatment of symptomatic gastroparesis (ClinicalTrials.gov NCT02466711).

Keywords: gastric accommodation; gastric motility; gastroparesis; ghrelin receptor agonist; satiation.

Conflict of interest statement

Dr. Camilleri serves on an advisory board of Rhythm Pharmaceuticals (Boston, Massachusetts, USA), with compensation to his employer, Mayo Clinic, and no personal financial remuneration. The other authors have no competing interests.

© 2016 John Wiley & Sons Ltd.

Figures

Figure 1

Gastroduodenal manometry in healthy subjects who were randomized to relamorelin (right panel) or placebo (left panel) showing manometric tracings in the postprandial period from the gastric body to the duodenum. Note the normal amplitude of contractions, with the marked increase in the frequency of contractions and the greater extent (relative to the pylorus) where antral contractions are recorded with relamorelin treatment.

Figure 2

Postprandial site of origin of detectable waves proximal to the pyloric antrum for placebo and relamorelin groups.

Figure 3

Examples of gastric volumes measured by SPECT. Note the similarity in the measured fasting and postprandial gastric volumes in the two examples treated with relamorelin or placebo.