title: Short-Term Effects of Relamorelin on Descending Colon Motility in Chronic Constipation: A Randomized, Controlled Trial.
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.
  
  
  OBJECTIVE
  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.
authors.affiliation: 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. acostacardenas.andres@mayo.edu.
authors.forename: Andres
authors.initials: A
authors.lastname: Acosta
authors.affiliation: 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. camilleri.michael@mayo.edu.
authors.forename: Michael
authors.initials: M
authors.lastname: Camilleri
authors.affiliation: 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. busciglio.irene@mayo.edu.
authors.forename: Irene
authors.initials: I
authors.lastname: Busciglio
authors.affiliation: 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. boldingh.amy@mayo.edu.
authors.forename: Amy
authors.initials: A
authors.lastname: Boldingh
authors.affiliation: 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. nelson.alfred@mayo.edu.
authors.forename: Alfred D
authors.initials: AD
authors.lastname: Nelson
authors.affiliation: 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. burton.duane@mayo.edu.
authors.forename: Duane
authors.initials: D
authors.lastname: Burton
mesh_terms: D000328:Adult; D002908:Chronic Disease; D044683:Colon, Descending / Q000187:drug effects*; D003187:Compliance / Q000187:drug effects; D003248:Constipation / Q000188:drug therapy*; D004311:Double-Blind Method; D005260:Female; D005769:Gastrointestinal Motility / Q000187:drug effects*; D006801:Humans; D008297:Male; D008365:Manometry; D008875:Middle Aged; D009842:Oligopeptides / Q000494:pharmacology* / Q000627:therapeutic use; D010528:Peristalsis / Q000187:drug effects
chemical_list: D009842:Oligopeptides; C000593860:relamorelin
keywords: Colonic transit; Constipation; Ghrelin agonist