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

ABSTRACT: 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.To measure pharmacological effects of relamorelin on gastric accommodation, distal antral motility, and satiation in healthy volunteers.In a placebo-controlled, double-blind, randomized study of 16 healthy volunteers, we compared effects of 30 ?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.Relamorelin, 30 ?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 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.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).

SUBMITTER: Nelson AD

PROVIDER: S-EPMC5083171 | biostudies-literature | 2016 Nov

REPOSITORIES: biostudies-literature

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

Nelson A D AD Camilleri M M Acosta A A Busciglio I I Linker Nord S S Boldingh A A Rhoten D D Ryks M M Burton D D

Neurogastroenterology and motility 20160609 11

<h4>Background</h4>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.<h4>Aim</h4>To measure pharmacological effects of relamorelin on gastric accommodation, distal antral motility, and satiation in healthy volunteers.<h4>Methods</h4>In a placebo-controlled, double-blind, randomized stu ...[more]

PMID: 27283792

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Project description:Kappa opioid receptors (KORs) have been characterized as an aversive system in the brain and implicated in social behavior in preclinical models. This work investigated the effect of social status on the KOR system in humans using positron emission tomography (PET) imaging with the novel KOR agonist radiotracer [11C]EKAP. Eighteen healthy participants (mean age 41.2?±?9.3) completed the Barratt Simplified Measure of Social Status (BSMSS), an MRI and an [11C]EKAP PET scan on the High Resolution Research Tomograph. Arterial blood sampling and metabolite analysis were conducted to obtain the input function. Regions of interest were based upon an MR template and included the reward/aversion areas of the brain. The multilinear analysis-1 (MA1) method was applied to the regional time-activity curves (TACs) to calculate [11C]EKAP regional volume of distribution (VT). Mixed models and Pearson correlation coefficients were used for body mass index (BMI), gender and age, with age being dropped in subsequent analyses because of nonsignificance. An overall effect of primary ROIs (F7,?112 7.43, p?<?0.0001), BSMSS score (F1,?13 7.45, p?=?0.02), BMI (F1,?13 23.5, p?<?0.001), and gender (F1,?13 23.75, p?<?0.001), but not age (F1,?13 1.12, p?=?0.35) was observed. Regional [11C]EKAP VT and BSMSS were found to be negatively correlated in the amygdala (r?=?-0.69, p?<?0.01), anterior cingulate cortex (r?=?-0.56, p?=?0.02), caudate (r?=?-0.66, p?<?0.01), frontal cortex (r?=?-0.52, p?=?0.04), hippocampus (r?=?-0.60, p?=?0.01), pallidum (r?=?-0.59, p?=?0.02), putamen (r?=?-0.62, p?=?0.01), and ventral striatum (r?=?-0.66, p?<?0.01). In secondary (non-reward) regions, correlations of [11C]EKAP VT and BSMSS were nonsignificant with the exception of the insula. There was an inverse correlation between social status and KOR levels that was largely specific to the reward/aversion (e.g., saliency) areas of the brain. This finding suggests the KOR system may act as a mediator for the negative effects of social behaviors in humans.

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

Publications

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

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