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Open Access 01-12-2019 | Irritable Bowel Syndrome | Study protocol

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

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

Published in: Trials | Issue 1/2019

Abstract

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 5HT₃ 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.

Available only for authorised users

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Title: Treatment of irritable bowel syndrome with diarrhoea using titrated ondansetron (TRITON): study protocol for a randomised controlled trial
Authors: David Gunn
Ron Fried
Rabia Lalani
Amanda Farrin
Ivana Holloway
Tom Morris
Catherine Olivier
Rachael Kearns
Maura Corsetti
Mark Scott
Adam Farmer
Anton Emmanuel
Peter Whorwell
Yan Yiannakou
David Sanders
John Mclaughlin
Kapil Kapur
Maria Eugenicos
Ayesha Akbar
Nigel Trudgill
Lesley Houghton
Phil G. Dinning
Alexander C. Ford
Qasim Aziz
Robin Spiller
Publication date: 01-12-2019
Publisher: BioMed Central
Keywords: Irritable Bowel Syndrome
Diarrhea
Diarrhea
Key Symptom
Abdominal Pain
Published in: Trials / Issue 1/2019
Electronic ISSN: 1745-6215
DOI: https://doi.org/10.1186/s13063-019-3562-6

At a glance: The STEP trials

Springer Medicine

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

Abstract

Background

Methods

Discussion

Trial registration

At a glance: The STEP trials

Springer Medicine

Abstract

Background

Methods

Discussion

Trial registration

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