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


OBJECTIVE
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.


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
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).
Clinical Enteric Neuroscience Translational and Epidemiological Research (CENTER), Mayo Clinic, Rochester, MN, USA.
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AD
Nelson
Clinical Enteric Neuroscience Translational and Epidemiological Research (CENTER), Mayo Clinic, Rochester, MN, USA. camilleri.michael@mayo.edu.
M
M
Camilleri
Clinical Enteric Neuroscience Translational and Epidemiological Research (CENTER), Mayo Clinic, Rochester, MN, USA.
A
A
Acosta
Clinical Enteric Neuroscience Translational and Epidemiological Research (CENTER), Mayo Clinic, Rochester, MN, USA.
I
I
Busciglio
Clinical Enteric Neuroscience Translational and Epidemiological Research (CENTER), Mayo Clinic, Rochester, MN, USA.
S
S
Linker Nord
Clinical Enteric Neuroscience Translational and Epidemiological Research (CENTER), Mayo Clinic, Rochester, MN, USA.
A
A
Boldingh
Clinical Enteric Neuroscience Translational and Epidemiological Research (CENTER), Mayo Clinic, Rochester, MN, USA.
D
D
Rhoten
Clinical Enteric Neuroscience Translational and Epidemiological Research (CENTER), Mayo Clinic, Rochester, MN, USA.
M
M
Ryks
Clinical Enteric Neuroscience Translational and Epidemiological Research (CENTER), Mayo Clinic, Rochester, MN, USA.
D
D
Burton
D000328:Adult; D004311:Double-Blind Method; D005260:Female; D064368:Healthy Volunteers; D006801:Humans; D008297:Male; D008365:Manometry / Q000379:methods; D009842:Oligopeptides / Q000494:pharmacology*; D011706:Pyloric Antrum / Q000187:drug effects* / Q000502:physiology; D054440:Receptors, Ghrelin / Q000819:agonists* / Q000502:physiology; D012527:Satiation / Q000187:drug effects* / Q000502:physiology
D009842:Oligopeptides; D054440:Receptors, Ghrelin; C000593860:relamorelin
gastric accommodation; gastric motility; gastroparesis; ghrelin receptor agonist; satiation