TReatment of Irritable Bowel Syndrome With Diarrhoea Using Titrated ONdansetron Trial

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%, 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) 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\>\>. Exclusion Criteria: 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\>\>.