TReatment of Irritable Bowel Syndrome With Diarrhoea Using Titrated ONdansetron Trial

NCT03555188 | Completed Phase 3 DMC

• 1 other identifier: 15/74/01
• Study Type: interventional
• Target: 80
• Locations: 1 country
• Sites: 14

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.

Conditions

IBS - Irritable Bowel Syndrome

Keywords

Diarrhoea

Outcome Measures

Primary Outcomes (1)

• Weekly responder for abdominal pain and stool consistency

  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.

  12 weeks

Secondary Outcomes (14)

• Stool Frequency

  12 weeks

• Stool Consistency

  12 weeks

• Urgency of defecation

  12 weeks

• Satisfactory relief of IBS symptoms

  12 weeks c

• 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).

Other Outcomes (5)

• Colonic transit

  12 weeks

• Ondansetron and cyclical retrograde propagated contractions in the sigmoid colon

  12 weeks

• Ondansetron and rectal compliance/pressure thresholds for pain/urgency.

  12 weeks

Study Arms (2)

Ondansetron

EXPERIMENTAL

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

Drug: Ondansetron

Placebo

PLACEBO COMPARATOR

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

Drug: Ondansetron

Interventions

Ondansetron DRUG

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

Ondansetron; Placebo

Eligibility Criteria

• Age: 18 Years - 100 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Written (signed and dated) informed consent.
• Considered fit for study participation.
• Meeting Rome IV criteria for IBS-D
• Aged ≥ 18 years
• Undergone standardised workup to exclude the following alternative diagnoses:
• Microscopic colitis (colonoscopy or flexible sigmoidoscopy),

You may not qualify if:

• Lactose malabsorption.
• Coeliac disease (tTG or duodenal biopsy)
• 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).
• For women of child bearing potential, a negative pregnancy test should be performed within 72 hours of confirmation of eligibility.
• Weekly average worst pain score \>= X on a 0 to 100 point scale \<\<redacted to prevent patient bias\>\>.
• Any stools with a consistency of X on the Bristol Stool Form score (BSFS) for X day per week\<\<redacted to prevent patient bias\>\>.
• Gastrectomy
• Intestinal resection
• Other known organic GI diseases (e.g. Inflammatory bowel disease - Crohns disease, Ulcerative colitis.)
• 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
• QTc interval ≥450msec for men and ≥470msec for women. Assessed within the last 3 months by a 12-lead ECG.
• Previous chronic use of ondansetron or contraindications to it (rare as per BNF)
• 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.
• Women who are pregnant or breastfeeding
• 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.

Sponsors & Collaborators

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

Study Sites (14)

Barnsley Hospital NHS Foundation Trust

Barnsley, United Kingdom

Location

Sandwell and West Birmingham Hospitals NHS Trust

Birmingham, United Kingdom

Location

County Durham and Darlington NHS Foundation Trust

Durham, United Kingdom

Location

Westen General Hosptal, Edinburgh

Edinburgh, United Kingdom

Location

Leeds Teaching Hospitals NHS Trust

Leeds, United Kingdom

Location

London North West NHS Foundation Trust

London, United Kingdom

Location

Queen Mary, University of London

London, United Kingdom

Location

University College London Hospitals NHS Foundation Trust

London, United Kingdom

Location

Salford Royal Hospital

Manchester, United Kingdom

Location

University Hospital of South Manchester

Manchester, United Kingdom

Location

SouthTees Hospitals NHS FoundationTrust

Middlesbrough, United Kingdom

Location

Nottingham University Hospitals NHS Trust

Nottingham, United Kingdom

Location

Royal Hallamshire Hospital

Sheffield, United Kingdom

Location

University Hospitals of North Midlands NHS Trust

Stoke, United Kingdom

Location

Related Publications (1)

• 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.

  PMID: 36866724 RESULT

MeSH Terms

Conditions

Irritable Bowel Syndrome; Diarrhea

Interventions

Ondansetron

Condition Hierarchy (Ancestors)

Colonic Diseases, Functional; Colonic Diseases; Intestinal Diseases; Gastrointestinal Diseases; Digestive System Diseases; Signs and Symptoms, Digestive; Signs and Symptoms; Pathological Conditions, Signs and Symptoms

Intervention Hierarchy (Ancestors)

Imidazoles; Azoles; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds; Carbazoles; Indoles; Heterocyclic Compounds, 2-Ring; Heterocyclic Compounds, Fused-Ring; Heterocyclic Compounds, 3-Ring

Study Officials

• Robin Spiller

  University of Nottingham

  STUDY CHAIR

Study Design

• Study Type: interventional
• Phase: phase 3
• Allocation: RANDOMIZED
• Masking: DOUBLE
• Who Masked: PARTICIPANT, INVESTIGATOR
• Masking Details: This is a double-blinded study.
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Model Details: TRITON is a parallel group, randomised, double-blinded, placebo controlled trial, to determine the superiority of Ondansetron.

Study Record Dates

• First Submitted: April 18, 2018
• First Posted: June 13, 2018
• Study Start: March 29, 2018
• Primary Completion: August 3, 2020
• Study Completion: September 10, 2020
• Last Updated: August 7, 2023

Record last verified: 2023-08

Data Sharing

• IPD Sharing: Will not share

Locations

GB (14)