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

作者信息

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

机构信息

Clinical Enteric Neuroscience Translational and Epidemiological Research (CENTER), Mayo Clinic, Rochester, MN, USA.

出版信息

Neurogastroenterol Motil. 2016 Nov;28(11):1705-1713. doi: 10.1111/nmo.12870. Epub 2016 Jun 9.


DOI:10.1111/nmo.12870
PMID:27283792
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC5083171/
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 MI (p = 0.055) and numerically increased MI (p = 0.139) and MI (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).

摘要

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[1]
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本文引用的文献

[1]
Relamorelin Reduces Vomiting Frequency and Severity and Accelerates Gastric Emptying in Adults With Diabetic Gastroparesis.

Gastroenterology. 2016-4-4

[2]
Short-Term Effects of Relamorelin on Descending Colon Motility in Chronic Constipation: A Randomized, Controlled Trial.

Dig Dis Sci. 2016-3

[3]
Relamorelin Relieves Constipation and Accelerates Colonic Transit in a Phase 2, Placebo-Controlled, Randomized Trial.

Clin Gastroenterol Hepatol. 2015-5-19

[4]
Emerging treatments in Neurogastroenterology: relamorelin: a novel gastrocolokinetic synthetic ghrelin agonist.

Neurogastroenterol Motil. 2015-3

[5]
Preclinical gastrointestinal prokinetic efficacy and endocrine effects of the ghrelin mimetic RM-131.

Life Sci. 2014-7-25

[6]
The ghrelin agonist RM-131 accelerates gastric emptying of solids and reduces symptoms in patients with type 1 diabetes mellitus.

Clin Gastroenterol Hepatol. 2013-4-30

[7]
Simplifying the measurement of gastric accommodation using SPECT.

Neurogastroenterol Motil. 2013-2-17

[8]
Clinical guideline: management of gastroparesis.

Am J Gastroenterol. 2012-11-13

[9]
Randomized controlled phase Ib study of ghrelin agonist, RM-131, in type 2 diabetic women with delayed gastric emptying: pharmacokinetics and pharmacodynamics.

Diabetes Care. 2012-9-6

[10]
Performance characteristics of the measurement of gastric volume using single photon emission computed tomography.

Neurogastroenterol Motil. 2011-1-6

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