- Fecal Incontinence
|Treatment of irritable bowel syndrome with diarrhoea using titrated ondansetron (TRITON): study protocol for a randomised controlled trial
Gunn D1,2, Fried R3, Lalani R4, Farrin A5, Holloway I5, Morris T5, Olivier C5, Kearns R5, Corsetti M2, Scott M3, Farmer A6, Emmanuel A7, Whorwell P8, Yiannakou Y9, Sanders D10, Mclaughlin J11, Kapur K12, Eugenicos M13, Akbar A14, Trudgill N15, Houghton L16, Dinning PG17, Ford AC16, Aziz Q3, Spiller R18,19. Trials. 2019 Aug 20;20(1):517. doi: 10.1186/s13063-019-3562-6.
1 NIHR Nottingham Digestive Diseases Biomedical Research Centre, University of Nottingham, Nottingham, UK.
2 Nottingham Digestive Diseases Centre, Nottingham University Hospitals NHS Trust, Nottingham, UK.
3 Barts and The London School of Medicine and Dentistry, Queen Mary University of London, London, UK.
4 Wingate Institute of Neurogastroenterology, Queen Mary University of London, London, UK.
5 Clinical Trials Research Unit, Leeds Institute of Clinical Trials Research, University of Leeds, Leeds, UK.
6 Royal Stoke Hospital, University Hospitals of North Midlands NHS Trust, Stoke, UK.
7 University College London Hospital, University College London Hospitals NHS Foundation Trust, London, UK.
8 Wythenshawe Hospital, Manchester University NHS Foundation Trust, Manchester, UK.
9 County Durham and Darlington Foundation Trust, University Hospital of North Durham, Durham, UK.
10 Royal Hallamshire Hospital, Sheffield Teaching Hospitals NHS Foundation Trust, Sheffield, UK.
11 Salford Royal NHS Foundation Trust, Salford Royal University Hospital, Manchester, UK.
12 Barnsley Hospital, Barnsley Hospital NHS Foundation Trust, Barnsley, UK.
13 Western General Hospital Edinburgh, NHS Lothian, Edinburgh, UK.
14 London North West Healthcare NHS Trust, St Mark's Hospital, London, UK.
15 Sandwell General Hospital, Sandwell and West Birmingham Hospitals NHS Trust, Birmingham, UK.
16 St James's Hospital, Leeds Teaching Hospitals NHS Trust, Leeds, UK.
17 Discipline of Surgery and Gastroenterology, Flinders Medical Centre, Flinders University, Adelaide, South Australia, Australia.
18 NIHR Nottingham Digestive Diseases Biomedical Research Centre, University of Nottingham, Nottingham, UK. firstname.lastname@example.org.
19 Nottingham Digestive Diseases Centre, Nottingham University Hospitals NHS Trust, Nottingham, UK. email@example.com.
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.
ISRCTN, ISRCTN17508514 , Registered on 2 October 2017.