Visceral hypersensitivity is a pivotal mechanism in pain associated with irritable bowel syndrome (IBS). Calcitonin gene-related peptide (CGRP) is expressed by visceral afferents. The aim of this study was to evaluate the efficacy of rimegepant, a CGRP antagonist, on abdominal pain, rectal compliance and sensation, gut transit, and safety in participants with nonconstipation IBS with pain. We conducted a pilot, randomized, double-blind, placebo-controlled, parallel-group design trial (NCT06221111) of oral rimegepant 75 mg every other day (as approved for migraine prophylaxis) in adults with nonconstipation IBS pain. The trial consisted of three periods: 2-wk run-in, 4-wk treatment, and 4-wk post-treatment with diary recording of daily abdominal pain (primary endpoint) and bowel movements (BMs). Rectal compliance and sensation were measured using barostat distensions and gastrointestinal and colonic transit by scintigraphy. Statistical analysis compared rimegepant with placebo using analysis of covariance with sex, level of anxiety, and baseline measurements as covariates. Twenty-four participants were randomized to rimegepant ( = 12) or placebo ( = 12); baseline demographics, rectal sensation, and compliance were similar between the groups. Rimegepant did not significantly reduce abdominal pain, daily BM frequency, or BM consistency relative to baseline. Compared with placebo, rimegepant significantly reduced sensations of gas, urgency, and pain during 24 mmHg, and gas and urgency sensations during 36 mmHg rectal distension (all ≤ 0.05 unadjusted). Rimegepant decreased rectal compliance. No significant effects were noted during washout. There were no serious adverse events or adverse events of ≥ Grade 3 severity. Rimegepant's effects on rectal sensation suggest further studies in nonconstipation IBS pain are warranted. Clinical Trial Registry Number: NCT06221111. This pilot, randomized, double-blind trial in a relatively small sample of patients with IBS-related pain shows rimegepant significantly reduced sensations of gas, urgency, and pain during rectal distention and decreased rectal compliance. Decrease in compliance implies that changes in physical properties or distensibility of rectum did not contribute to alterations in rectal sensation. Same dose of rimegepant did not significantly impact daily abdominal pain, BM frequency, or colonic transit. There were no serious adverse events.
Keywords: abdominal, bowel movements, calcitonin gene-related peptide, compliance, rectal
American journal of physiology. Gastrointestinal and liver physiology
Journal Article
English
41637861
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