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

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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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Acknowledgments

The authors thank Mrs. Cindy Stanislav for excellent secretarial assistance.

Funding

Rhythm Pharmaceuticals provided medication and a grant to cover part of the cost of this research study, which was otherwise funded by Mayo Clinic. Dr. M. Camilleri’s research on colonic motility is supported in part by NIH R01-DK92179.

Author contributions

Andres Acosta is a fellow co-investigator and co-author and contributed toward screening of patients. Michael Camilleri is the principal investigator, helped with endoscopy and placement of colonic device, and author of manuscript. Amy Boldingh is the study coordinator and recruited participants. Irene Busciglio is the colonic motility technician and analyzed data. Alfred D. Nelson is a fellow co-investigator and co-author and contributed toward screening of patients. Duane Burton is the laboratory supervisor and analyzed data.

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Authors and Affiliations

  1. Clinical Enteric Neuroscience Translational and Epidemiological Research (CENTER), Division of Gastroenterology and Hepatology, Mayo Clinic, Charlton 8-110, 200 First St. S.W., Rochester, MN, 55905, USA

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

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  1. Andres Acosta
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  2. Michael Camilleri
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Correspondence to Michael Camilleri.

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Conflict of interest

Dr. Camilleri serves on the advisory board of Rhythm Pharmaceuticals with payment for his services to his employer, Mayo Clinic. The other authors have no conflicts of interest.

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Acosta, A., Camilleri, M., Busciglio, I. et al. Short-Term Effects of Relamorelin on Descending Colon Motility in Chronic Constipation: A Randomized, Controlled Trial. Dig Dis Sci 61, 852–860 (2016). https://doi.org/10.1007/s10620-015-3876-5

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  • DOI: https://doi.org/10.1007/s10620-015-3876-5

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