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Effects of ghrelin receptor agonist, relamorelin, on gastric motor functions and satiation in healthy volunteers
Author(s) -
Nelson A. D.,
Camilleri M.,
Acosta A.,
Busciglio I.,
Linker Nord S.,
Boldingh A.,
Rhoten D.,
Ryks M.,
Burton D.
Publication year - 2016
Publication title -
neurogastroenterology and motility
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.489
H-Index - 105
eISSN - 1365-2982
pISSN - 1350-1925
DOI - 10.1111/nmo.12870
Subject(s) - postprandial , medicine , gastric emptying , antrum , gastroparesis , placebo , agonist , endocrinology , ghrelin , stomach , gastroenterology , gastric distension , receptor , insulin , pathology , alternative medicine
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 μ g 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 μ g 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 MI 0‐15 ( p = 0.055) and numerically increased MI 0‐60 ( p = 0.139) and MI 16‐30 ( 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 NCT 02466711).