Fig. 1

Schedule of enrolment, interventions and assessments throughout the TRITON study. ¹ Date of birth, National Health Service (NHS) number, address, telephone number (if consented to text messages), smoking history, height, weight. ² White blood cell count (WBC), full blood count (FBC), liver function tests (LFTs), urea and electrolytes (UEs), C-reactive protein (CRP). ³ Titrated to optimum dose during the first 2 weeks. ⁴ Recording worst abdominal pain (0–100), worst urgency (0–100), number of investigational medicinal product (IMP) taken, use of loperamide, stool consistency of each stool passed, and relief from irritable bowel syndrome (IBS) symptoms at the end of each week. ⁵ Asking if they have passed a stool type 6 or 7, and what their worst abdominal pain score was that day. ⁶ At baseline only, Physical Symptoms Questionnaire (PHQ)-12; at baseline and visits, IBS Severity Scoring System (IBS-SSS), Short-form Leeds Dyspepsia Questionnaire (SF-LDQ), Hospital Anxiety and Depression Scale (HADS), and IBS Quality of Life Questionnaire (IBS-QOL). ⁷ Six high-rectal biopsies taken either during mechanistic assessment or at visit 3. ⁸ Whole blood (5 ml) at visit 3; serum (5 ml) at visits 3 and 5. ⁹ Four aliquots obtained and frozen at home prior to visit. ¹⁰ Performed at University of Nottingham & QMUL only (n = 40); patients will receive additional payment for participation. ¹¹ Performed at Nottingham/Leeds/QMUL/UCL only (n = 80); patients will receive additional payment for participation