Authors' objectives: Many patients with ulcerative colitis report ongoing diarrhoea even when their disease is stable and in remission.

Authors' results and conclusions: The MODULATE trial opened in December 2021 and closed in January 2023. Of the eight secondary care sites that completed contracting, only four opened to recruitment during this time, and one person was randomised. Trial timelines coincided with the start of the COVID-19 pandemic, causing substantial delays and, ultimately, its early closure. During this time, the trial underwent two major redesign phases, enabling a fully remote participant pathway incorporating electronic consent, remote data capture, posted blood and stool sample kits for eligibility screening, delivery of the dietary intervention via telephone or video call platform, postage of trial investigational medicinal products directly to participants’ homes and all trial follow-up appointments conducted via telephone. The second phase of redesign pushed the trial towards a fully decentralised model. However, this stage was not implemented due to the decision to close the trial early. Although the trial closed early and with insufficient participants to proceed with full statistical analysis, lessons were learnt that could potentially inform future remote trial design and decentralised participant pathways.

Authors' methods: MODULATE was a pragmatic, multicentre, seamless, adaptive, phase 2/3 open-label, parallel-group, multiarm multistage randomised controlled trial. People aged over 18 years with stable ulcerative colitis who had diarrhoea, recruited from secondary care sites in the United Kingdom. The control arm consisted of modified first-line dietary advice given to all patients with irritable bowel syndrome; the first interventional arm was amitriptyline, a tricyclic antidepressant, which at low doses slows colonic transit; the second intervention was loperamide, an antidiarrhoeal drug also thought to slow colonic transit; the third was ondansetron, an antiemetic thought to slow colonic transit; and the fourth was a diet low in fermentable oligo-, di-, and mono-saccharides and polyols, which is thought to reduce bloating and gas within the small intestine. All patients randomised to an interventional arm were to receive treatment for 6 months. Phase 2: Improvement in diarrhoea measured using the Gastrointestinal Symptom Rating Scale-irritable bowel syndrome questionnaire at 8 weeks post randomisation: improvement defined as those reporting minor discomfort from diarrhoea or less (scoring ≤ 2 on the diarrhoea subscale). The study was unable to recruit the necessary sample size, preventing the trial from progressing. The trial met with several challenges. The Trial Steering Committee’s root cause analysis concluded that the pandemic was the leading factor in trial closure, especially regarding our ability to recruit both sites and participants.

Project Status: Completed

URL for project: https://www.journalslibrary.nihr.ac.uk/programmes/hta/17/33/03

Year Published: 2025

URL for published report: https://www.journalslibrary.nihr.ac.uk/hta/published-articles/GHFE4871

URL for additional information: English

English language abstract: An English language summary is available

Publication Type: Full HTA

Country: England, United Kingdom

DOI: 10.3310/GHFE4871

Organisation Name: NIHR Health Technology Assessment programme

Contact Address: NIHR Journals Library, National Institute for Health and Care Research, Evaluation, Trials and Studies Coordinating Centre, Alpha House, University of Southampton Science Park, Southampton SO16 7NS, UK

Contact Name: journals.library@nihr.ac.uk

Contact Email: journals.library@nihr.ac.uk