Journal Article

Treatment of irritable bowel syndrome with diarrhoea using titrated ondansetron (TRITON): study protocol for a randomised controlled trial

Farmer, Adam, Trudgill, Nigel, Houghton, Lesley, Spiller, Robin, Dinning, Phil G., Yiannakou, Yan, Gunn, David, Lalani, Rabia, Whorwell, Peter, Mclaughlin, John, Morris, Tom, Emmanuel, Anton, Corsetti, Maura, Eugenicos, Maria, Akbar, Ayesha, Holloway, Ivana, Aziz, Qasim, Kearns, Rachael, Kapur, Kapil, Olivier, Catherine, Scott, Mark, Farrin, Amanda, Sanders, David, Ford, Alexander C., Fried, Ron

2019

Overview

Background Irritable bowel syndrome with diarrhoea (IBS-D) affects up to 4% of the general population. Symptoms include frequent, loose, or watery stools with associated urgency, resulting in marked reduction of quality of life and loss of work productivity. Ondansetron, a 5HT 3 receptor antagonist, has had an excellent safety record for over 20 years as an antiemetic, yet is not widely used in the treatment of IBS-D. It has, however, been shown to slow colonic transit and in a small randomised, placebo-controlled, cross-over pilot study, benefited patients with IBS-D. Methods This trial is a phase III, parallel group, randomised, double-blind, multi-centre, placebo-controlled trial, with embedded mechanistic studies. Participants ( n = 400) meeting Rome IV criteria for IBS-D will be recruited from outpatient and primary care clinics and by social media to receive either ondansetron (dose titrated up to 24 mg daily) or placebo for 12 weeks. Throughout the trial, participants will record their worst abdominal pain, worst urgency, stool frequency, and stool consistency on a daily basis. The primary endpoint is the proportion of “responders” in each group, using Food and Drug Administration (FDA) recommendations. Secondary endpoints include pain intensity, stool consistency, frequency, and urgency. Mood and quality of life will also be assessed. Mechanistic assessments will include whole gut transit, faecal tryptase and faecal bile acid concentrations at baseline and between weeks 8 and 11. A subgroup of participants will also undergo assessment of sensitivity ( n  = 80) using the barostat, and/or high-resolution colonic manometry ( n  = 40) to assess motor patterns in the left colon and the impact of ondansetron. Discussion The TRITON trial aims to assess the effect of ondansetron across multiple centres. By defining ondansetron’s mechanisms of action we hope to better identify patients with IBS-D who are likely to respond. Trial registration ISRCTN, ISRCTN17508514 , Registered on 2 October 2017.

• Publisher: BioMed Central,BioMed Central Ltd,Springer Nature B.V,BMC
• Subject: Abdomen / Acids / Antidiarrheals - adverse effects / Antidiarrheals - therapeutic use / Barostat / Bile / Bile acids / Biomedicine / Blood / Clinical trials / Clinical Trials, Phase III as Topic / Complications and side effects / Constipation / Deoxycholic acid / Diarrhea / Diarrhea - diagnosis / Diarrhea - drug therapy / Diarrhea - etiology / Diarrhea - physiopathology / Diarrhoea / Dosage and administration / Double-Blind Method / Drug dosages / Drug therapy / Health Sciences / High-resolution manometry / Humans / Inflammatory bowel disease / Irritable bowel syndrome / Irritable Bowel Syndrome - complications / Irritable Bowel Syndrome - diagnosis / Irritable Bowel Syndrome - drug therapy / Irritable Bowel Syndrome - physiopathology / Ischemia / Medical research / Medicine / Medicine & Public Health / Motility / Multicenter Studies as Topic / Ondansetron / Ondansetron - adverse effects / Ondansetron - therapeutic use / Pain / Production management / Quality of life / Questionnaires / Randomized Controlled Trials as Topic / Serotonin / Serotonin 5-HT3 Receptor Antagonists - adverse effects / Serotonin 5-HT3 Receptor Antagonists - therapeutic use / Social media / Statistics for Life Sciences / Study Protocol / Time Factors / Treatment Outcome / United Kingdom