Irritable Bowel Syndrome with Diarrhoea MedDRA version: 20.1 Level: LLT Classification code 10060845 Term: Diarrhea predominant irritable bowel syndrome System Organ Class: 100000004856 MedDRA version: 21.1 Level: LLT Classification code 10060849 Term: Diarrhoea predominant irritable bowel syndrome System Organ Class: 100000004856
Conditions
Interventions
Product Name: Ondansetron
Pharmaceutical Form: Capsule
Concentration unit: mg milligram(s)
Concentration type: equal
Concentration numbe
Sponsors
Nottingham University Hospitals NHS Trust
Eligibility
Sex/Gender
All
Inclusion criteria
Inclusion criteria: Patients must fulfil all of the following criteria. 1. Written (signed and dated) informed consent. 2. Considered fit for study participation. 3. Meeting Rome IV criteria for IBS-D (see Appendices) 4. Aged = 18 years 5. Undergone standardised workup to exclude the following alternative diagnoses a) Microscopic colitis (colonoscopy or flexible sigmoidoscopy), within previous 2 years b) Bile acid diarrhoea (SeHCAT results of > 10%, C4 results of =65 years) yes F.1.3.1 Number of subjects for this age range 10
Exclusion criteria
Exclusion criteria: Patients must not fulfil any of the following criteria: 1. Gastrectomy 2. Intestinal resection 3. Other known organic GI diseases (e.g. inflammatory bowel disease – Crohn’s disease, ulcerative colitis). 4. Unable or unwilling to stop restricted medication including regular loperamide, antispasmodics (e.g. buscopan, mebeverine, peppermint oil, alverine citrate), eluxadoline, tricyclic antidepressant doses >30mg/day or other drugs likely in the opinion of the investigator to alter bowel habit. These medicines should be discontinued for a 7 day washout period prior to registration. Note: Intermittent loperamide will be permitted but only as rescue medication (see section 8.7) 5. QTc interval =450msec for men and =470msec for women. Assessed within the last 3 months by a 12-lead ECG. 6. Previous chronic use of ondansetron or contraindications to it (rare as per BNF) 7. Pulse, blood pressure, laboratory blood values outside the normal ranges according to the site’s local definition of normal. Assessed within the last 3 months. Note: Minor rises in ALT (<2 x upper limit of normal) will be acceptable but the patient’s GP will be informed if they remain elevated at end of the study. 8. Women who are pregnant or breastfeeding 9. Patients currently participating or who have been in an IMP trial in the previous three months where the use of the IMP may cause issues with the assessment of causality in this study. 10. Currently taking SSRIs or tricyclic antidepressants (unless at a stable dose for at least 3 months and with no plan to change the dose during the study). 11. Currently taking and unwilling or unable to stop any of the prohibited medications.* * Prohibited medications – Apomorphine & tramadol which interact with ondansetron. Caution should be taken with patients on QT prolonging drugs and cardio toxic drugs. These patients should be reviewed by the PI to determine if they are suitable for the study. 12. Patients with only stools of consistency 7 on the Bristol Stool Form score (BSFS) for 7 days a week. ^^ ^^ Exclusion criterion 12 will be assessed after the patient has completed the 14 day pre-treatment daily stool and pain diary and returned at visit 2.
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Main Objective: Does 12 weeks treatment with Ondansetron improve symptoms on pain and loose stools in patients with irritable bowel syndrome with diarrhoea compared to placebo?;Secondary Objective: What effect can be seen with Ondansetron on stool frequency, consistency, urgency of defecation, satisfactory relief of IBS symptoms and use of rescue medication and abdominal pain over 12 weeks of treatment?; Primary end point(s): The primary endpoint will be defined, as recommended by the FDA, as a patient being a weekly responder for BOTH pain intensity AND stool consistency for at least 6 weeks in the 12 week follow-up period. Weekly responder status is defined as follows: 1. Weekly responder for Abdominal Pain Intensity: • At least 30% decrease from baseline in weekly average of worst daily abdominal pain score (abdominal pain score measured on a 0 to 100 point scale in past 24 hours) 2. Weekly responder for Stool Consistency: • A decrease of at least 50% in the number of days per week with at least one loose stool consistency (BSFS = 6 or 7) compared with baseline. To achieve success in the primary endpoint, a patient must be a weekly responder for both pain and for consistency during the same 6 weeks within the 12 week follow-up period. ;Timepoint(s) of evaluation of this end point: The primary endpoint will be measured at 12 weeks post randomisation. | — |
Secondary
| Measure | Time frame |
|---|---|
| Secondary end point(s): What is the estimated treatment effect of ondansetron in relation to stool frequency, consistency, urgency of defecation, satisfactory relief of IBS symptoms and use of rescue medication and abdominal pain over 12 weeks of treatment? 1. Stool frequency will be defined as number of stools per day up to 12 weeks post randomisation using patient’s diary. For the endpoint analysis, the mean number of stools per day over the last month (weeks 9-12) will be used. 2. a. Stool consistency will be defined as number of days per week with at least 1 loose stool b. Average stool consistency over the last month (weeks 9-12) Consistency will be assessed daily by Bristol Stool Form Score (BSFS) and a loose stool is defined as BSFS >5. For the endpoint analyses, the mean number of days per week with at least 1 loose stool over last month (weeks 9-12) and the mean daily stool consistency over the last month (weeks 9-12) will be used. 3. Urgency of defecation (on a scale 0-100) For the endpoint analyses, the mean daily urgency score over last month (weeks 9-12) will be used. 4. Satisfactory relief of IBS symptoms will be defined as moderate or significant relief of IBS symptoms for at least 6 out of 12 weeks For the endpoint analyses, the proportion of patients with satisfactory relief of symptoms will be used. 5. Score of functional dyspepsia Questionnaire For the endpoint analyses, the functional dyspepsia score at 12 weeks will be used. 6. Score of IBS Symptom Severity Scale Questionnaire for IBS (IBS-SSS) For the endpoint analyses, the IBS-SSS score at 12 weeks will be used. 7. Use of rescue medication will be defined as use of loperamide and assessed by total number of days having to take l | — |
Countries
United Kingdom
Contacts
Public ContactLorna Barnard
University of Leeds
Outcome results
None listed