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Digestive Diseases and Sciences
Published in: Digestive Diseases and Sciences 3/2016

01-03-2016 | Original Article

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

Authors: Andres Acosta, Michael Camilleri, Irene Busciglio, Amy Boldingh, Alfred D. Nelson, Duane Burton

Published in: Digestive Diseases and Sciences | Issue 3/2016

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Abstract

Background

The pentapeptide ghrelin agonist, relamorelin, accelerates colonic transit in patients with chronic constipation (CC). In a murine model, relamorelin decreased excitability of colonic circular smooth muscle cells and colonic intraluminal pressure.

Aim

To determine short-term effects of relamorelin on colonic motility measured by barostat and multilumen manometry in CC.

Methods

In a placebo-controlled, single-dose, double-blind, randomized study in patients with CC, we investigated the motor effects of relamorelin, 100 μg, SQ (12 patients) compared to placebo SQ (six patients). A motility-barostat balloon assembly was used to measure colonic compliance; tone and phasic pressure activity were measured before and after a 1000-kcal milkshake meal (administered ~60 min post-medication). Overall “background” phasic pressure activity was assessed by: average amplitude and motility index (MI = ln[sum amplitudes × #contractions + 1]) over defined periods. High-amplitude propagating contractions (HAPCs) were characterized by amplitude >75 mmHg and propagating contractions >50 mmHg; both were propagated over at least 10 cm. Postprandial HAPCs were the primary end point. The study sample had 80 % power to detect an increase of 3.3 HAPCs in the hour post-meal.

Results

Relamorelin, 100 μg, significantly induced more pre-meal propagated contractions [PCs of either >50 or >75 mmHg] compared to placebo (p < 0.05). Relamorelin also induced more post-meal PCs >50 or >75 mmHg than placebo. Relamorelin did not significantly alter colonic compliance, fasting or postprandial phasic pressure activity (20 min pre-meal fasting MI) or tone, and 60 min postprandial phasic pressure amplitude or MI, or tone.

Conclusions

Relamorelin stimulates propagated colonic contractions without alteration of background irregular contractions in CC.
ClinicalTrial.Gov registration number: NCT 01781104.
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Metadata
Title
Short-Term Effects of Relamorelin on Descending Colon Motility in Chronic Constipation: A Randomized, Controlled Trial
Authors
Andres Acosta
Michael Camilleri
Irene Busciglio
Amy Boldingh
Alfred D. Nelson
Duane Burton
Publication date
01-03-2016
Publisher
Springer US
Published in
Digestive Diseases and Sciences / Issue 3/2016
Print ISSN: 0163-2116
Electronic ISSN: 1573-2568
DOI
https://doi.org/10.1007/s10620-015-3876-5

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