TReatment of Irritable Bowel Syndrome With Diarrhoea Using Titrated ONdansetron Trial

NCT ID: NCT03555188

Last Updated: 2023-08-07

Study Results

Results pending

The study team has not published outcome measurements, participant flow, or safety data for this trial yet. Check back later for updates.

Basic Information

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Recruitment Status

COMPLETED

Clinical Phase

PHASE3

Total Enrollment

80 participants

Study Classification

INTERVENTIONAL

Study Start Date

2018-03-29

Study Completion Date

2020-09-10

Brief Summary

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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

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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.

Conditions

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IBS - Irritable Bowel Syndrome

Study Design

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Allocation Method

RANDOMIZED

Intervention Model

PARALLEL

TRITON is a parallel group, randomised, double-blinded, placebo controlled trial, to determine the superiority of Ondansetron.
Primary Study Purpose

TREATMENT

Blinding Strategy

DOUBLE

Participants Investigators
This is a double-blinded study.

Study Groups

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Ondansetron

Taken orally 4mg-24mg daily for 12 weeks. Dose to be amended throughout according to symptoms.

Group Type EXPERIMENTAL

Ondansetron

Intervention Type DRUG

Ondansetron is a highly selective receptor antagonist (5-HT3RA)

Placebo

Taken orally 4mg-24mg daily for 12 weeks. Dose to be amended throughout according to symptoms.

Group Type PLACEBO_COMPARATOR

Ondansetron

Intervention Type DRUG

Ondansetron is a highly selective receptor antagonist (5-HT3RA)

Interventions

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Ondansetron

Ondansetron is a highly selective receptor antagonist (5-HT3RA)

Intervention Type DRUG

Eligibility Criteria

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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),

Exclusion Criteria

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\>\>.


1. Gastrectomy
2. Intestinal resection
3. Other known organic GI diseases (e.g. Inflammatory bowel disease - Crohns 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
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, FBC or LFTs 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 stools of consistency X on the Bristol Stool Form score (BSFS) for X days a week \<\<redacted to prevent patient bias\>\>.
Minimum Eligible Age

18 Years

Maximum Eligible Age

100 Years

Eligible Sex

ALL

Accepts Healthy Volunteers

No

Sponsors

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Barnsley Hospital NHS Foundation Trust

OTHER

Sponsor Role collaborator

Barts & The London NHS Trust

OTHER

Sponsor Role collaborator

County Durham and Darlington NHS Foundation Trust

OTHER_GOV

Sponsor Role collaborator

Flinders University

OTHER

Sponsor Role collaborator

The Leeds Teaching Hospitals NHS Trust

OTHER

Sponsor Role collaborator

London North West Healthcare NHS Trust

OTHER

Sponsor Role collaborator

NHS Lothian

OTHER_GOV

Sponsor Role collaborator

Queen Mary University of London

OTHER

Sponsor Role collaborator

Sandwell & West Birmingham Hospitals NHS Trust

OTHER

Sponsor Role collaborator

Sheffield Teaching Hospitals NHS Foundation Trust

OTHER

Sponsor Role collaborator

University College London Hospitals

OTHER

Sponsor Role collaborator

University Hospitals of North Midlands NHS Trust

OTHER

Sponsor Role collaborator

Manchester University NHS Foundation Trust

OTHER_GOV

Sponsor Role collaborator

University of Manchester

OTHER

Sponsor Role collaborator

National Institute for Health Research, United Kingdom

OTHER_GOV

Sponsor Role collaborator

University of Leeds

OTHER

Sponsor Role lead

Responsible Party

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Responsibility Role SPONSOR

Principal Investigators

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Robin Spiller

Role: STUDY_CHAIR

University of Nottingham

Locations

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Barnsley Hospital NHS Foundation Trust

Barnsley, , United Kingdom

Site Status

Sandwell and West Birmingham Hospitals NHS Trust

Birmingham, , United Kingdom

Site Status

County Durham and Darlington NHS Foundation Trust

Durham, , United Kingdom

Site Status

Westen General Hosptal, Edinburgh

Edinburgh, , United Kingdom

Site Status

Leeds Teaching Hospitals NHS Trust

Leeds, , United Kingdom

Site Status

London North West NHS Foundation Trust

London, , United Kingdom

Site Status

Queen Mary, University of London

London, , United Kingdom

Site Status

University College London Hospitals NHS Foundation Trust

London, , United Kingdom

Site Status

Salford Royal Hospital

Manchester, , United Kingdom

Site Status

University Hospital of South Manchester

Manchester, , United Kingdom

Site Status

SouthTees Hospitals NHS FoundationTrust

Middlesbrough, , United Kingdom

Site Status

Nottingham University Hospitals NHS Trust

Nottingham, , United Kingdom

Site Status

Royal Hallamshire Hospital

Sheffield, , United Kingdom

Site Status

University Hospitals of North Midlands NHS Trust

Stoke, , United Kingdom

Site Status

Countries

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United Kingdom

References

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Gunn D, Topan R, Barnard L, Fried R, Holloway I, Brindle R, Corsetti M, Scott M, Farmer A, Kapur K, Sanders D, Eugenicos M, Trudgill N, Whorwell P, Mclaughlin J, Akbar A, Houghton L, Dinning PG, Aziz Q, Ford AC, Farrin AJ, Spiller R. Randomised, placebo-controlled trial and meta-analysis show benefit of ondansetron for irritable bowel syndrome with diarrhoea: The TRITON trial. Aliment Pharmacol Ther. 2023 Jun;57(11):1258-1271. doi: 10.1111/apt.17426. Epub 2023 Mar 3.

Reference Type RESULT
PMID: 36866724 (View on PubMed)

Other Identifiers

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15/74/01

Identifier Type: -

Identifier Source: org_study_id

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