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

Digestive diseases and sciences, 2016-03, Vol.61 (3), p.852-860 [Peer Reviewed Journal]

Springer Science+Business Media New York 2015 ;COPYRIGHT 2016 Springer ;Springer Science+Business Media New York 2016 ;ISSN: 0163-2116 ;EISSN: 1573-2568 ;DOI: 10.1007/s10620-015-3876-5 ;PMID: 26467700 ;CODEN: DDSCDJ

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Title:
Short-Term Effects of Relamorelin on Descending Colon Motility in Chronic Constipation: A Randomized, Controlled Trial
Author: Acosta, Andres ; Camilleri, Michael ; Busciglio, Irene ; Boldingh, Amy ; Nelson, Alfred D. ; Burton, Duane
Subjects: Adult ; Biochemistry ; Chronic Disease ; Colon, Descending - drug effects ; Comparative analysis ; Compliance - drug effects ; Constipation ; Constipation - drug therapy ; Double-Blind Method ; Female ; Gastroenterology ; Gastrointestinal Motility - drug effects ; Hepatology ; Humans ; Male ; Manometry ; Medical research ; Medicine ; Medicine & Public Health ; Medicine, Experimental ; Middle Aged ; Oligopeptides - pharmacology ; Oligopeptides - therapeutic use ; Oncology ; Original Article ; Peristalsis - drug effects ; Pneumoviridae ; Transplant Surgery
Is Part Of: Digestive diseases and sciences, 2016-03, Vol.61 (3), p.852-860
Description: 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.
Publisher: New York: Springer US
Language: English
Identifier: ISSN: 0163-2116
EISSN: 1573-2568
DOI: 10.1007/s10620-015-3876-5
PMID: 26467700
CODEN: DDSCDJ
Source: MEDLINE
ProQuest Central

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

Springer Science+Business Media New York 2015 ;COPYRIGHT 2016 Springer ;Springer Science+Business Media New York 2016 ;ISSN: 0163-2116 ;EISSN: 1573-2568 ;DOI: 10.1007/s10620-015-3876-5 ;PMID: 26467700 ;CODEN: DDSCDJ

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