IBS - Irritable Bowel Syndrome
Conditions
Keywords
Diarrhoea
Brief summary
A placebo controlled study to determine the efficacy and mode of action of ondansetron in the treatment of irritable bowel syndrome with diarrhoea.
Detailed description
Irritable bowel syndrome (IBS) affects around 10% of the population and accounts for 1.8 million consultations/year in primary care in England and Wales (0.6 million patients). Around one third of patients meet the criteria for IBS with diarrhoea (IBS-D) and despite its high prevalence, there is no satisfactory treatment at present. Loperamide is currently used to reduce bowel frequency, however it does not improve symptoms such abdominal pain. Other symptoms of IBS-D include frequent, loose, or watery stools with associated urgency, which can severely limit socialising, travelling, and eating out, resulting in a reduced quality of life and work productivity. The primary aim of the study is to determine the effectiveness and safety of the use of ondansetron in patients with the symptoms of IBS-D including urgency, looseness of stool, frequency of defecation and abdominal discomfort. Ondansetron belongs to a class of drug known as 5HT3RAs and a recent meta-analysis shows that 5HT3RAs is an effective treatment for IBS-D, improving stool consistency and reducing frequency and urgency of defecation. 400 patients with IBS-D will be randomised on a 1:1 basis to receive either Ondansetron or Placebo. Both treatments will be administered in oral doses of between 4-24mg daily for 12 weeks. Dose titration will be undertaken in the first two weeks of the study to avoid constipation. The primary outcome of response will be assessed at 12 weeks post randomisation using patient reported data on daily stool frequency and abdominal pain. If ondansetron is effective in the trial, it could easily be widely adopted since it is an inexpensive, safe, and generic drug. By providing an effective treatment, it could not only reduce patient symptoms, but also reduce costs of repeated referral and investigation.
Interventions
DRUGOndansetron
Ondansetron is a highly selective receptor antagonist (5-HT3RA)
Sponsors
Barnsley Hospital NHS Foundation Trust
Barts & The London NHS Trust
County Durham and Darlington NHS Foundation Trust
Flinders University
The Leeds Teaching Hospitals NHS Trust
London North West Healthcare NHS Trust
NHS Lothian
Queen Mary University of London
Sandwell & West Birmingham Hospitals NHS Trust
Sheffield Teaching Hospitals NHS Foundation Trust
University College London Hospitals
University Hospitals of North Midlands NHS Trust
Manchester University NHS Foundation Trust
University of Manchester
National Institute for Health Research, United Kingdom
University of Leeds
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
DOUBLE (Subject, Investigator)
Masking description
This is a double-blinded study.
Intervention model description
TRITON is a parallel group, randomised, double-blinded, placebo controlled trial, to determine the superiority of Ondansetron.
Eligibility
Sex/Gender
ALL
Age
18 Years to 100 Years
Healthy volunteers
No
Inclusion criteria
1. Written (signed and dated) informed consent. 2. Considered fit for study participation. 3. Meeting Rome IV criteria for IBS-D 4. Aged ≥ 18 years 5. Undergone standardised workup to exclude the following alternative diagnoses: 1. Microscopic colitis (colonoscopy or flexible sigmoidoscopy), 2. Bile acid diarrhoea (SeHCAT results of \> 10%, C4 results of \<19 ng/ml or failed 1 week trial of a bile acid binding agent \[colestyramine 4g t.d.s. , colesevelam 625mg t.d.s. or equivalent\]) within previous 5 years, Note: Cholecystectomy will not be an
Exclusion criteria
if bile acid diarrhoea has been excluded. Patients with SeHCAT values of 5-10% will be eligible if they fail to respond to a 1 week trial of bile acid binding agent (see above) 3. Lactose malabsorption. 4. Coeliac disease (tTG or duodenal biopsy) 6. Patients of child bearing potential or with partners of child bearing potential must agree to use methods of medically acceptable forms of contraception during the study and for 90 days after completion of study drug, (e.g. implants, injectable, combined oral contraceptives, barrier methods, true abstinence (when this is in line with the preferred and usual lifestyle of the patient) or vasectomised partners). 7. For women of child bearing potential, a negative pregnancy test should be performed within 72 hours of confirmation of eligibility. 8. Weekly average worst pain score \>= X on a 0 to 100 point scale \<\<redacted to prevent patient bias\>\>. 9. Any stools with a consistency of X on the Bristol Stool Form score (BSFS) for X day per week\<\<redacted to prevent patient bias\>\>.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Weekly responder for abdominal pain and stool consistency | 12 weeks | Measured at 12 weeks post randomisation and defined, as recommended by the FDA, as patient being a weekly responder for BOTH pain intensity AND stool consistency for at least 6 weeks in the 12 week treatment period. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| IBS Symptom Severity Scale | This information is collected at baseline (week 0) and again after treatment (week 12). | Irritable Bowel Syndrome Symptom Severity Scale questionnaire which asks patients about their IBS symptoms such as abdominal pain etc. The patients will provide yes/no answer or a score on a 0-100 scale with 0 being the minimum amount and 100 being define as quite severe/definitely. |
| IBS Quality of life summary score | This information is collected via a questionnaire which asks the patient about the quality of their life. This information is collected at baseline (week 0) and again after treatment (week 12). | IBS-QOL questionnaire at 0 and 12 weeks |
| Stool frequency post treatment | 4 weeks | The mean number of stools per day for 1 months after treatment (weeks 13-16) |
| Stool consistency post treatment | 4 weeks | The mean daily stool consistency over 1 month (weeks 13-16) . |
| Urgency of defecation post treatment | 4 weeks | The mean daily urgency score over 1 month post treatment (weeks 13-16). |
| Abdominal pain post treatment | 4 weeks | The mean daily pain score over 1 month (weeks 13-16) |
| Functional dyspepsia | This information is collected via a questionnaire which asks the patient about any symptoms associated with IBS that they may be experiencing. This information is collected at baseline (week 0) and again after treatment (week 12). | SF-LDQ questionnaire at week 0 and week 12 |
| Stool Frequency | 12 weeks | For the endpoint analysis, the mean number of stools per day over the last month (weeks 9-12) will be used. |
| Stool Consistency | 12 weeks | Defined as number of days per week with at least 1 loose stool and the average stool consistency over the last month (weeks 9-12) |
| Urgency of defecation | 12 weeks | The mean daily urgency score over last month (weeks 9-12) |
| Satisfactory relief of IBS symptoms | 12 weeks c | Defined as satisfactory relief of IBS symptoms for at least 6 out of 12 weeks |
| Rescue Medication | 12 weeks | The total number of days taken loperamide throughout the 12 weeks |
| Abdominal pain score | 12 weeks | The mean daily pain score over the last month (weeks 9-12) |
| Hospital Anxiety and Depression Scale | This information is collected at baseline (week 0) and again after treatment (week 12). | Hospital Anxiety and Depression Scale questionnaire. This information is collected via a questionnaire which asks the patient about their general overall feelings. It asks a variety of question and the patient is to tick the box beside the reply that is closest to how they feel. Each question has 1 of 4 potential replies (feelings) that vary depending on the nature of the question. |
Other
| Measure | Time frame | Description |
|---|---|---|
| Ondansetron and rectal compliance/pressure thresholds for pain/urgency. | 12 weeks | Barostat assessment at baseline and week 12 |
| Does ondansetron reduce total faecal bile acids and total tryptase and does the reduction correlate with changes in urgency? | 12 weeks | Stool samples collected at baseline and week 12 |
| Do polymorphisms in the TPH-1 gene predict response to ondansetron and does this alter 5-HT or TPH1-mRNA | 12 weeks | Bloods and biopsies taken at baseline and week 12 |
| Ondansetron and cyclical retrograde propagated contractions in the sigmoid colon | 12 weeks | High resolution colonic manometry at baseline and week 12 |
| Colonic transit | 12 weeks | Colonic Transit study to determine if ondansetron slows colonic transit. |
Countries
United Kingdom
Outcome results
None listed