TReatment of Irritable Bowel Syndrome With Diarrhoea Using Titrated ONdansetron Trial

• Status: Unknown status
• Trial end date: 2020-02-28
• Target enrollment: 0
• Participant gender: All

Summary

A placebo controlled study to determine the efficacy and mode of action of ondansetron in the treatment of irritable bowel syndrome with diarrhoea.

• Phase: Phase 3
• Accepts Healthy Volunteers?: No

Details

• Lead Sponsor: University of Leeds
• Collaborators: Barnsley Hospital NHS Foundation Trust; Barts & The London NHS Trust; County Durham and Darlington NHS Foundation Trust; Flinders University; London North West Healthcare NHS Trust; Lothian Health Board; Manchester University NHS Foundation Trust; National Institute for Health Research, United Kingdom; NHS Lothian; Queen Mary University of London; Sandwell & West Birmingham Hospitals NHS Trust; Sheffield Teaching Hospitals NHS Foundation Trust; The Leeds Teaching Hospitals NHS Trust; University College London Hospitals; University Hospitals of North Midlands NHS Trust; University of Manchester
• Treatments: Ondansetron

Criteria

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% or C4 results of <19 ng/ml), Note:

Cholecystectomy will not be an exclusion criteria if bile acid diarrhoea has been excluded

3. Lactose malabsorption.

4. Coeliac disease (tTG or duodenal biopsy)

6. All patients 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, 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 >= 30 on a 0 to 100 point scale.

9. Any stools with a consistency of 6 or 7 on the Bristol Stool Form score (BSFS) for 2 -6 day per week.

Exclusion Criteria:

1. Gastrectomy

2. Intestinal resection

3. Other known organic GI diseases (e.g. Inflammatory bowel disease - Crohns disease, Ulcerative colitis.)

4. Inability to stop anti-diarrhoeal drugs for the duration of the study.

5. QTc interval >=420msec. 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, FBC or LFTs outside the normal ranges according to the site's local definition of normal. Assessed within the last 3 months.

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. Patients taking SSRIs or tricyclic antidepressants are not excluded if on a stable dose for at least 3 months and with no plan to change the dose during the study.

11. Patients currently taking any of the restricted medications.*

• Restricted medications - Apomorphine, Tramadol & medications likely to alter bowel habit (in the opinion of the investigator).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.