Amitriptyline at low-dose and titrated for irritable bowel syndrome as second-line treatment (The ATLANTIS trial): protocol for a randomised double-blind placebo-controlled trial in primary care
Sarah L. Alderson,
Alexandra Wright-Hughes,
Alexander C. Ford,
Amanda Farrin,
Suzanne Hartley,
Catherine Fernandez,
Christopher Taylor,
Pei Loo Ow,
Emma Teasdale,
Daniel Howdon,
Elspeth Guthrie,
Robbie Foy,
Matthew J. Ridd,
Felicity L. Bishop,
Delia Muir,
Matthew Chaddock,
Amy Herbert,
Deborah Cooper,
Ruth Gibbins,
Sonia Newman,
Heather Cook,
Roberta Longo,
Hazel Everitt
Affiliations
Sarah L. Alderson
School of Medicine, Leeds Institute of Health Sciences, University of Leeds, University of Leeds
Alexandra Wright-Hughes
Clinical Trial Research Unit, Leeds Institute of Clinical Trials Research, School of Medicine, University of Leeds
Alexander C. Ford
Leeds Gastroenterology Institute, St James’s University Hospital
Amanda Farrin
Clinical Trial Research Unit, Leeds Institute of Clinical Trials Research, School of Medicine, University of Leeds
Suzanne Hartley
Clinical Trial Research Unit, Leeds Institute of Clinical Trials Research, School of Medicine, University of Leeds
Catherine Fernandez
Clinical Trial Research Unit, Leeds Institute of Clinical Trials Research, School of Medicine, University of Leeds
Christopher Taylor
Clinical Trial Research Unit, Leeds Institute of Clinical Trials Research, School of Medicine, University of Leeds
Pei Loo Ow
Clinical Trial Research Unit, Leeds Institute of Clinical Trials Research, School of Medicine, University of Leeds
Emma Teasdale
Centre for Clinical and Community Applications of Health Psychology, School of Psychology, University of Southampton
Daniel Howdon
School of Medicine, Leeds Institute of Health Sciences, University of Leeds, University of Leeds
Elspeth Guthrie
School of Medicine, Leeds Institute of Health Sciences, University of Leeds, University of Leeds
Robbie Foy
School of Medicine, Leeds Institute of Health Sciences, University of Leeds, University of Leeds
Matthew J. Ridd
Population Health Sciences, Bristol Medical School, University of Bristol
Felicity L. Bishop
Centre for Clinical and Community Applications of Health Psychology, School of Psychology, University of Southampton
Delia Muir
Clinical Trial Research Unit, Leeds Institute of Clinical Trials Research, School of Medicine, University of Leeds
Matthew Chaddock
Let’s Cure IBS
Amy Herbert
Population Health Sciences, Bristol Medical School, University of Bristol
Deborah Cooper
School of Medicine, Leeds Institute of Health Sciences, University of Leeds, University of Leeds
Ruth Gibbins
Primary Care Research Centre, Faculty of Medicine, University of Southampton
Sonia Newman
Primary Care Research Centre, Faculty of Medicine, University of Southampton
Heather Cook
Exeter Clinical Trials Unit, University of Exeter
Roberta Longo
School of Medicine, Leeds Institute of Health Sciences, University of Leeds, University of Leeds
Hazel Everitt
Primary Care Research Centre, Faculty of Medicine, University of Southampton
Abstract Background Irritable bowel syndrome (IBS) is a common functional bowel disorder that has a considerable impact on patient quality of life and substantial societal and health care resource costs. Current treatments are often ineffective. Tricyclic antidepressants have shown promise in secondary care populations but their effectiveness in a primary care setting remains unclear. Methods ATLANTIS is a randomised, multi-centre, parallel-group, two-arm, double-blind, placebo-controlled trial of low-dose amitriptyline as a second-line treatment for IBS in primary care. Participants will be invited by letter, or recruited opportunistically, from general practices in three regions of England (West Yorkshire, Wessex, and West of England) and screened for eligibility. A total of 518 adult patients with IBS, who are symptomatic despite first-line therapies, will be randomised 1:1 to amitriptyline or identical placebo for 6 months. Treatment will commence at a dose of 10 mg (or one placebo tablet) daily at night, with dose titration up to a maximum of 30 mg at night, depending on side effects and response to treatment. Participant-reported assessments will be conducted at baseline and 3, 6, and 12 months post-randomisation. The primary objective is to determine the effectiveness of amitriptyline, compared with placebo, in improving participant-reported global symptoms of IBS at 6 months (using the IBS Severity Scoring System). Secondary outcomes include relief of IBS symptoms, effect on IBS-associated somatic symptoms (Patient Health Questionnaire-12), anxiety and depression (Hospital Anxiety and Depression Scale), ability to work and participate in other activities (Work and Social Adjustment Scale), acceptability and tolerability of treatment, self-reported health care use, health-related quality of life (EQ-5D-3L), and cost-effectiveness. A nested, qualitative study will explore patient and general practitioner experiences of treatments and trial participation, including acceptability, adherence, unanticipated effects, and implications for wider use of amitriptyline for IBS in primary care. Discussion Determining the clinical and cost-effectiveness of low-dose amitriptyline as a second-line treatment for IBS in primary care will provide robust evidence to inform management decisions. Trial registration ISRCTN ISRCTN48075063 . Registered on 7th June 2019.
