TRITON Trial v1.0
Research type
Research Study
Full title
TReatment of Irritable bowel syndrome using Titrated ONdansetron Trial
IRAS ID
219133
Contact name
Robin Charles Spiller
Contact email
Sponsor organisation
Nottingham University Hospitals NHS Trust
Eudract number
2017-000533-31
Duration of Study in the UK
3 years, 7 months, 30 days
Research summary
Research Summary
Irritable bowel syndrome (IBS) with diarrhoea (IBS-D) is a common condition characterised by recurrent abdominal pain with frequent, loose stools passed with urgency. Such patients may have an excess of serotonin (5-hydroxytryptamine [5-HT)) in their intestine which stimulates movement through the bowel (transit) and secretion. Ondansetron is a drug which blocks the 5-HT receptor, which is used to treat nausea, and has an excellent safety record. We have encouraging pilot data that Ondansetron slows transit and improves IBS-D symptoms. We now wish to find out how it work . We will measure bowel contractions using a new high resolution system and bowel relaxation by assessing pressure during rectal distension with a balloon to determine whether these changes are related to improved symptoms. We will also measure total bile acid concentrations and the amount of pancreatic enzyme, tryptase, in the stools as these may sensitise the rectum causing urgency. The response to ondansetron may depend upon genetic factors so we will assess the variation in the gene controlling the rate of 5HT production. We will perform a trial in which we treat patients with Ondansetron or a placebo (a dummy tablet without any effect) and compare the change in symptoms. After confirming the diagnosis patients will be randomly assigned to take either Ondansetron or placebo for 12 weeks while recording symptoms. Neither the patient nor the study team will know which treatment the patient receives until the end of the trial to avoid any bias. We will repeat our measurements in the 12th week to see the effect of the drug compared to placebo. The study will confirm if Ondansetron works in IBS, improve our ability to predict who will respond to Ondansetron and exactly how it works, so newer better drugs can be developed for this common but poorly understood condition.
Summary of Results
Background: Irritable bowel syndrome with diarrhoea (IBS-D) is characterised by frequent, loose, or watery stools with marked reduction of quality of life. Pilot data suggests ondansetron benefits patients with IBS-D.
Methods: A randomised clinical trial in 80 patients meeting Rome IV criteria for IBS-D from 18 centres throughout the UK. Patients received either ondansetron or placebo for 12 weeks but their allocation was concealed from both investigator and patient. They recorded their worst abdominal pain, stool frequency and consistency daily. The primary endpoint was the proportion of patients meeting the FDA criteria for being a “responder” meaning they showed benefit to both pain and days with loose stool. Secondary endpoints included pain intensity, stool consistency, frequency,. We also measured the time for content to pass through the gut (whole gut transit time [WGTT]).
Results: Mean (95% CI) The study closed early due to slow recruitment with just 80 patients randomised. There were 40.5 % of “responders” in the ondansetron arm and 27.9 % in the placebo arm however due to low numbers these differences could be due to chance. There was a significant difference in average stool consistency in the final month of treatment. WGTT increased significantly more on ondansetron, increasing from baseline to 12 weeks by a mean of by 3.8 hours while it fell 2.2 hours on placebo.
Conclusion –These results are consistent with previous studies showing ondansetron improves stool consistency and slows transit. However being underpowered the apparent improvement in responder rate could have been due to chance. A further larger trial is needed to confirm the benefit of ondansetron which should be done in primary care where most patients are to be found.REC name
Yorkshire & The Humber - Leeds West Research Ethics Committee
REC reference
17/YH/0262
Date of REC Opinion
7 Nov 2017
REC opinion
Further Information Favourable Opinion