TY - JOUR
T1 - Treatment of irritable bowel syndrome with diarrhoea using titrated ondansetron (TRITON)
T2 - Study protocol for a randomised controlled trial
AU - Gunn, David
AU - Fried, Ron
AU - Lalani, Rabia
AU - Farrin, Amanda
AU - Holloway, Ivana
AU - Morris, Tom
AU - Olivier, Catherine
AU - Kearns, Rachael
AU - Corsetti, Maura
AU - Scott, Mark
AU - Farmer, Adam
AU - Emmanuel, Anton
AU - Whorwell, Peter
AU - Yiannakou, Yan
AU - Sanders, David
AU - McLaughlin, John
AU - Kapur, Kapil
AU - Eugenicos, Maria
AU - Akbar, Ayesha
AU - Trudgill, Nigel
AU - Houghton, Lesley
AU - Dinning, Phil G.
AU - Ford, Alexander C.
AU - Aziz, Qasim
AU - Spiller, Robin
PY - 2019/8/20
Y1 - 2019/8/20
N2 - 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.
AB - 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.
KW - Barostat
KW - Diarrhoea
KW - High-resolution manometry
KW - Irritable bowel syndrome
KW - Ondansetron
UR - http://www.scopus.com/inward/record.url?scp=85071132192&partnerID=8YFLogxK
U2 - 10.1186/s13063-019-3562-6
DO - 10.1186/s13063-019-3562-6
M3 - Article
C2 - 31429811
AN - SCOPUS:85071132192
SN - 1745-6215
VL - 20
JO - Trials
JF - Trials
IS - 1
M1 - 517
ER -
