IBS - Irritable Bowel SyndromePhase 3TRITONNCT03555188
TReatment of Irritable Bowel Syndrome With Diarrhoea Using Titrated ONdansetron Trial
A Phase 3 study testing Ondansetron in people with IBS - Irritable Bowel Syndrome, run by University of Leeds at 14 sites in United Kingdom.
Trial summary
A placebo controlled study to determine the efficacy and mode of action of ondansetron in the treatment of irritable bowel syndrome with diarrhoea. Read more about this study
- Who is it for?
- Ages 18 to 100 years
- Conditions the study is for
- IBS - Irritable Bowel Syndrome
- What is being tested?
- Ondansetron
- Type of treatment
- Pill or oral medicine
- Could I receive a placebo?
- Yes, some participants may receive a placebo
- How many people
- 80 participants
- Where
- 14 sitesUnited Kingdom
- Study dates
- 29 Mar 2018to 10 Sep 2020
- Phase
- Phase 3
- Are there results?
- None posted in the registry
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 to 100 years
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- 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),
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- 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)
- 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>>.
Who cannot join
- 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)
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- 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.
- 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).
- 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.
- Patients with stools of consistency X on the Bristol Stool Form score (BSFS) for X days a week <<redacted to prevent patient bias>>.
Trial locations and contacts
14 sites in 1 country.
14 sites in 1 country
United Kingdom14 sites
Barnsley Hospital NHS Foundation Trust
Barnsley
Sandwell and West Birmingham Hospitals NHS Trust
Birmingham
County Durham and Darlington NHS Foundation Trust
Durham
Westen General Hosptal, Edinburgh
Edinburgh
Leeds Teaching Hospitals NHS Trust
Leeds
London North West NHS Foundation Trust
London
Queen Mary, University of London
London
University College London Hospitals NHS Foundation Trust
London
Salford Royal Hospital
Manchester
University Hospital of South Manchester
Manchester
SouthTees Hospitals NHS FoundationTrust
Middlesbrough
Nottingham University Hospitals NHS Trust
Nottingham
Royal Hallamshire Hospital
Sheffield
University Hospitals of North Midlands NHS Trust
Stoke
About this study
Official title: A Randomised, Placebo Controlled Trial to Determine the Efficacy and Mode of Action of Ondansetron in the Treatment of Irritable Bowel Syndrome With Diarrhoea
A placebo controlled study to determine the efficacy and mode of action of ondansetron in the treatment of irritable bowel syndrome with diarrhoea.
Read the 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.
- Conditions
- IBS - Irritable Bowel Syndrome
- Being tested
- Ondansetron
- Keywords
- Diarrhoea
- Medical subject headings
- Irritable Bowel Syndrome, Diarrhea
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
OndansetronDrug
Ondansetron is a highly selective receptor antagonist (5-HT3RA)
| Study group | Role | What they receive |
|---|---|---|
| Ondansetron | Experimental | Taken orally 4mg-24mg daily for 12 weeks. Dose to be amended throughout according to symptoms. Receives: Drug: Ondansetron |
| Placebo | Placebo comparator | Taken orally 4mg-24mg daily for 12 weeks. Dose to be amended throughout according to symptoms. Receives: Drug: Ondansetron |
What is being measured
The primary outcome is the main question the study is designed to answer.
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.
Measured: 12 weeks
Secondary outcomes (14)
Stool Frequency
For the endpoint analysis, the mean number of stools per day over the last month (weeks 9-12) will be used.
Measured: 12 weeks
Stool Consistency
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)
Measured: 12 weeks
Urgency of defecation
The mean daily urgency score over last month (weeks 9-12)
Measured: 12 weeks
Satisfactory relief of IBS symptoms
Defined as satisfactory relief of IBS symptoms for at least 6 out of 12 weeks
Measured: 12 weeks c
Functional dyspepsia
SF-LDQ questionnaire at week 0 and week 12
Measured: 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).
IBS Symptom Severity Scale
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.
Measured: This information is collected at baseline (week 0) and again after treatment (week 12).
Rescue Medication
The total number of days taken loperamide throughout the 12 weeks
Measured: 12 weeks
Abdominal pain score
The mean daily pain score over the last month (weeks 9-12)
Measured: 12 weeks
Hospital Anxiety and Depression Scale
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.
Measured: This information is collected at baseline (week 0) and again after treatment (week 12).
IBS Quality of life summary score
IBS-QOL questionnaire at 0 and 12 weeks
Measured: 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).
Stool frequency post treatment
The mean number of stools per day for 1 months after treatment (weeks 13-16)
Measured: 4 weeks
Stool consistency post treatment
The mean daily stool consistency over 1 month (weeks 13-16) .
Measured: 4 weeks
Urgency of defecation post treatment
The mean daily urgency score over 1 month post treatment (weeks 13-16).
Measured: 4 weeks
Abdominal pain post treatment
The mean daily pain score over 1 month (weeks 13-16)
Measured: 4 weeks
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted13 Jun 2018
- Study start29 Mar 2018
- Primary completion3 Aug 2020
- Study completion10 Sep 2020
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (1)Papers the sponsor has linked to this study.
- Other trials for IBS - Irritable Bowel SyndromeStudies of the same condition, open and under way.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 3
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Model description
- TRITON is a parallel group, randomised, double-blinded, placebo controlled trial, to determine the superiority of Ondansetron.
- Masking
- Double blind
- Who is masked
- Participant, Investigator
- Enrolment
- 80 participants (actual)
Sponsor and investigators
- Lead sponsor
- University of Leeds
- Sponsor type
- University, hospital or other
- Collaborators
- 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
- Responsible party
- Sponsor
- Investigators
- Robin Spiller, Study chair, University of Nottingham
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT03555188
- Sponsor's protocol ID
- 15/74/01
- Acronym
- TRITON
- Status last verified
- Aug 2023
- First submitted
- 18 Apr 2018
- Last updated
- 7 Aug 2023
- Results posted
- No
- Data monitoring committee
- Yes
- FDA-regulated drug
- No
- FDA-regulated device
- No
- Individual data sharing
- No
Publications
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.
PubMed 36866724
Study at a glance
From the registry record, last updated by the sponsor on 7 Aug 2023. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- A Randomised, Placebo Controlled Trial to Determine the Efficacy and Mode of Action of Ondansetron in the Treatment of Irritable Bowel Syndrome With Diarrhoea
- ClinicalTrials.gov ID
- NCT03555188
- Acronym / sponsor ID
- TRITON / 15/74/01
- Conditions
- IBS - Irritable Bowel Syndrome
- Keywords
- Diarrhoea
- Phase
- Phase 3
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 80 participants (actual)
- Lead sponsor
- University of LeedsUniversity, hospital or other
- Collaborators
- 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
- Study start
- 29 Mar 2018 (actual)
- Primary completion
- 3 Aug 2020 (actual)
- Study completion
- 10 Sep 2020 (actual)
- First posted
- 13 Jun 2018 (actual)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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.
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Double blind (participant, investigator)
- Number of arms
- 2
- Model description
- TRITON is a parallel group, randomised, double-blinded, placebo controlled trial, to determine the superiority of Ondansetron.
| Arm | Type | Receives |
|---|---|---|
| Ondansetron | Experimental | Drug: OndansetronTaken orally 4mg-24mg daily for 12 weeks. Dose to be amended throughout according to symptoms. |
| Placebo | Placebo comparator | Drug: OndansetronTaken orally 4mg-24mg daily for 12 weeks. Dose to be amended throughout according to symptoms. |
Who may qualify
- Ages
- 18 to 100 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (13 listed)
- 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:
Key exclusion criteria (13 listed)
- 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.
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| OndansetronOndansetron is a highly selective receptor antagonist (5-HT3RA) | Drug | Ondansetron, Placebo |
Primary outcome
Weekly responder for abdominal pain and stool consistency
Time frame: 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.
14 secondary outcomes
Stool Frequency
Time frame: 12 weeks
Stool Consistency
Time frame: 12 weeks
Urgency of defecation
Time frame: 12 weeks
Satisfactory relief of IBS symptoms
Time frame: 12 weeks c
Functional dyspepsia
Time frame: 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).
IBS Symptom Severity Scale
Time frame: This information is collected at baseline (week 0) and again after treatment (week 12).
Rescue Medication
Time frame: 12 weeks
Abdominal pain score
Time frame: 12 weeks
Hospital Anxiety and Depression Scale
Time frame: This information is collected at baseline (week 0) and again after treatment (week 12).
IBS Quality of life summary score
Time frame: 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).
Stool frequency post treatment
Time frame: 4 weeks
Stool consistency post treatment
Time frame: 4 weeks
Urgency of defecation post treatment
Time frame: 4 weeks
Abdominal pain post treatment
Time frame: 4 weeks
Results and safety
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 7 Aug 2023.
- Results publication: PubMed 36866724Gunn 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.
- Individual participant dataSharing planned: No
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Robin Spiller study chair
University of Nottingham
14 sites in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 3 study testing Ondansetron in people with IBS - Irritable Bowel Syndrome, run by University of Leeds at 14 sites in United Kingdom.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 13 inclusion and 13 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: finished, as of the sponsor's last update on 7 Aug 2023. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 14 sites in United Kingdom. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. Some participants in this study may receive a placebo. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 3 studies compare the treatment with the current standard treatment or a placebo in a large group, to confirm how well it works and watch for side effects.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Weekly responder for abdominal pain and stool consistency (time frame: 12 weeks). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT03555188, which also lists 1 linked publication.
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 7 Aug 2023.