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

• Published in: Neurogastroenterology and motility 2016-11, Vol.28 (11), p.1705-1713
• Main Authors: Nelson, A. D., Camilleri, M., Acosta, A., Busciglio, I., Linker Nord, S., Boldingh, A., Rhoten, D., Ryks, M., Burton, D.
• Format: Article
• Language: English
• Subjects: Adult; Double-Blind Method; Female; gastric accommodation; gastric motility; gastroparesis; ghrelin receptor agonist; Healthy Volunteers; Humans; Male; Manometry - methods; Oligopeptides - pharmacology; Pyloric Antrum - drug effects; Pyloric Antrum - physiology; Receptors, Ghrelin - agonists; Receptors, Ghrelin - physiology; satiation; Satiation - drug effects; Satiation - physiology
• ISSN: 1350-1925; 1365-2982
• DOI: 10.1111/nmo.12870

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). In 16 healthy volunteers, we compared effects of 30 µg subcutaneous (s.c.) relamorelin to placebo on: (i) gastric volumes measured by SPECT, (ii) 1‐h postprandial distal antral motility index (MI) by 15‐lumen perfusion gastroduodenal manometry, and (iii) satiation tested by Ensure nutrient drink test. Relamorelin, 30 µg s.c., significantly increased the number of contractions in the distal antrum during 0–60 min postmeal when compared to plac