Assessment of the effectiveness and safety of ethosuximide in the treatment of abdominal pain related to irritable bowel syndrome – IBSET: protocol of a randomised, parallel, controlled, double-blind and multicentre trial

Abstract

IntroductionIrritable bowel syndrome (IBS) is characterised by the association of abdominal chronic pain with bowel habit disorders in the absence of identifiable organic disease. This is the first reason for consultation in gastroenterology, with an estimated prevalence of 10%–15% in industrialised countries. Although this is a benign gastrointestinal disease, its chronicity profoundly impacts the patient’s quality of life and causes considerable health spending. Actual medical treatments are poorly efficient on IBS-related abdominal pain, making it a major public health concern. The mechanisms causing IBS symptoms are unknown. Recent studies have shown the involvement of T-type channel in abdominal pain. We aim to evaluate the therapeutic potential of ethosuximide, a T-type channel blocker, on the abdominal pain of patients presenting an IBS.Methods and analysisThe IBSET trial is a randomised, controlled, parallel, double-blind and multicentre study. It is the first clinical trial evaluating the efficacy and safety of ethosuximide on abdominal pain related to IBS. Adults with IBS that report significant abdominal pain (≥4/10) at least for 3 months will be included. 290 patients will be randomly assigned to receive either ethosuximide or placebo over 12 weeks after 1 week of run-in period. The primary endpoint is the rate of responders (pain reduction ≥30% and Subject Global Assessment of Relief score ≥4). The intensity of abdominal pain will be assessed by an 11-point Numerical Rating Scale before and after 12 weeks of treatment and the score of the Subject Global Assessment of Relief scale at the end of treatment. The secondary endpoints are the safety of ethosuximide, the intensity and features of IBS and quality of life.Ethics and disseminationThe study was approved by an independent medical ethics committee (CPP Sud-Est VI, Clermont-Ferrand, France). The results will be published in a peer-review journal and presented at international congresses.Trial registration numberNCT02973542; Pre-results.

A Potential Role of Ethosuximide and Pentoxifylline in Relieving Abdominal Pain in Irritable Bowel Syndrome Patients Treated with Mebeverine: A Randomized, Double-Blind, Placebo-Controlled Trial

“…A significant positive correlation was also identified between NGAL and NRS scores in group 2, and possibly reflected the role of ethosuximide in decreasing inflammatory cytokine levels in agreement with previous research. 2 …”

“… 1 A primary pathophysiological occurrence in IBS involves an altered intestinal epithelial barrier, which facilitates persistent low-grade mucosal inflammation resulting in visceral hypersensitivity (VH) and pain. 2 In several chronic pain animal models, hypersensitivity refers to increased excitability associated with ion channel expression remodeling. 3–5 In a case-controlled study, the Cav3.2 channel was found to be overexpressed in the colonic mucosa of individuals with IBS when compared with asymptomatic controls.…”

Inhibition of Cav3.2 calcium channels: A new target for colonic hypersensitivity associated with low‐grade inflammation

“…Importantly, in addition to demonstrating the pathophysiological role of these channels in CHS, these results recommend the prompt inception of clinical trials of ethosuximide, which is currently in clinical use. Accordingly, our team intends to investigate the effect of ethosuximide in IBS patients (Kerckhove, Scanzi, Pereira, Ardid, & Dapoigny, ) for a clinical proof of concept.…”

Chinese Herbal Medicine for Irritable Bowel Syndrome: A Meta-Analysis and Trial Sequential Analysis of Randomized Controlled Trials

“…The secondary outcomes included relief of abdominal pain and treatment-related adverse events. The relief of abdominal pain could be measured by visual analog scale (VAS) or other pain intensity rating scales like numeric rating scale, and a mean reduction for at least 30% compared with baseline was considered as relief of abdominal pain ( Chang et al, 2016 ; Kerckhove et al, 2017 ; Lembo et al, 2020 ). When the relief of abdominal pain was not reported, we contacted the authors to ask for relevant data to make the judgment.…”