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

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

Research output: Contribution to journalArticle

17 Citations (Scopus)

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 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.

Original languageEnglish (US)
Pages (from-to)852-860
Number of pages9
JournalDigestive Diseases and Sciences
Volume61
Issue number3
DOIs
StatePublished - Mar 1 2016

Fingerprint

Descending Colon
Constipation
Randomized Controlled Trials
Meals
Pressure
Placebos
Compliance
Fasting
Ghrelin
Manometry
relamorelin
Double-Blind Method
Smooth Muscle Myocytes

Keywords

  • Colonic transit
  • Constipation
  • Ghrelin agonist

ASJC Scopus subject areas

  • Gastroenterology
  • Physiology

Cite this

Short-Term Effects of Relamorelin on Descending Colon Motility in Chronic Constipation : A Randomized, Controlled Trial. / Acosta, Andres; Camilleri, Michael; Busciglio, Irene; Boldingh, Amy; Nelson, Alfred D.; Burton, Duane.

In: Digestive Diseases and Sciences, Vol. 61, No. 3, 01.03.2016, p. 852-860.

Research output: Contribution to journalArticle

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