Amitriptyline at Low-dose and Titrated for Irritable Bowel Syndrome as Second-line Treatment (The ATLANTIS study): A Double-blind Placebo-controlled Trial
Irritable Bowel syndrome (IBS) is common, causing abdominal pain, bloating and changes in bowel habit that can significantly affect quality of life. Many people suffer ongoing troublesome symptoms despite having been offered first line treatments. NICE IBS guidelines recommend low dose amitriptyline as a potential second-line treatment option but evidence for its use is limited and it is infrequently prescribed for IBS in primary care.The aim of this NIHR HTA funded ATLANTIS trial is to determine the clinical and cost-effectiveness of low-dose amitriptyline as a second-line treatment for IBS in primary care.
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 people with irritable bowel syndrome (IBS) in primary care. It includes an internal pilot and a nested, qualitative study. The aim is to recruit 518 participants from approximately 75 GP surgeries in 3 geographical areas: West Yorkshire, Wessex and , West of England, with the support of local Clinical Research Networks. Participants will be identified by searching GP lists for people with a diagnosis of IBS and sending of invite letters or by opportunistic recruitment when people present to the GP surgery. Those eligible after screening will be randomised to receive 6 months of trial treatment, taking either 1 to 3 tablets (10-30 mg) of amitriptyline or placebo once-daily. Participants will be able to titrate their dose (between 1 and 3 tablets) depending on symptoms and side effects. At 6 months participants will have the option to continue treatment for an additional 6 months (12 months total treatment).Outcome measures will be self-completed online or on paper (participant preference) at 3, 6, and 12 months following randomisation and a weekly question about relief of IBS symptoms. The primary outcome is IBS symptom severity score at 6 months. Secondary outcomes include the work and social adjustment scale, hospital anxiety and depression score (HADs), subjects global assessment of relief of IBS symptoms , quality of life using EQ5D and health care resource use to determine QALYs. A sub-sample of participants and recruiting GPs will undertake two semi-structured telephone interviews at 6 and 12 months to identify factors affecting the prescribing, acceptability and adherence of low-dose amitriptyline, and explore factors that might shape wider use of amitriptyline for IBS.
Trial set up and ethical approval has been completed and recruitment has begun. Reflections on the challenges of setting up this large RCT and initial recruitment figures will be presented at the conference
This large RCT will provide robust evidence on the clinical and cost effectiveness of amitriptyline for IBS in the primary care population and enable patients and clinicians to make better informed treatment decisions.