Irritable bowel syndrome Digestive System Irritable bowel syndrome
Conditions
Interventions
The overall aim of this study is to determine the clinical and cost-effectiveness of amitriptyline as a second-line treatment for IBS in primary care. The study aims to recruit 518 adult patients with
Sponsors
University of Leeds
Eligibility
Sex/Gender
All
Inclusion criteria
Inclusion criteria: 1. A diagnosis of IBS (of any subtype of stool pattern [diarrhoea, constipation, mixed]) in their primary care record, and fulfilling the Rome IV criteria 2. Age > = 18 years 3. Ongoing symptoms, defined as an IBS severity scoring system (IBS-SSS) score of > = 75 at screening, despite having tried dietary changes and first-line therapies as defined by NICE (antispasmodics [e.g. mebeverine], fibre supplements [e.g. fybogel], or anti-diarrhoeals [e.g. loperamide]), assessed at screening via patient self-report 4. A normal haemoglobin, total white cell count (WCC), and platelets within the last 6 months prior to screening 5. A normal CRP within the last 6 months prior to screening 6. Exclusion of coeliac disease, via anti-tTG antibodies, as per NICE guidance 7. No evidence of active suicidal ideation, as determined by three clinical screening questions below, and no recent history of self-harm (an episode of self-harm within the last 12 months prior to screening): 7.1. Whether the patient has experienced any thoughts of harming themselves, or ending their life in the last 7-10 days? 7.2. Whether the patient currently has any thoughts of harming themselves or ending their life? 7.3. Whether the patient has any active plans or ideas about harming themselves, or taking their life, in the near future? 8. If female, must be: 8.1. Postmenopausal (no menses for 12 months without an alternative medical cause), or 8.2. Surgically sterile (hysterectomy, bilateral salpingectomy or bilateral oophorectomy), or 8.3. Using highly effective contraception (must agree to be continued for 7 days after the last dose of the investigational medicinal product) 9. Able to complete questionnaires and trial assessments 10. Able to provide written informed consent
Exclusion criteria
Exclusion criteria: 1. Aged > 60 years and with no GP review in the 12 months prior to screening 2. Meeting locally adapted NICE 2-week referral criteria for suspected lower gastrointestinal cancer 3. A known documented diagnosis of inflammatory bowel disease or coeliac disease 4. A previous diagnosis of colorectal cancer 5. Patients currently participating in or who have been involved in any other CTIMP trial in the previous 3 months prior to screening 6. Pregnant or breastfeeding 7. Planning to become pregnant within the next 18 months 8. Current use of a TCA, or use of a TCA within the last 2 weeks prior to randomisation, for another indication 9. Allergy to TCAs 10. Other contraindications to the use of TCAs, including patients with any of the following: 10.1. Taking monoamine oxidase inhibitors (MAOIs), or receiving them within the last 2 weeks 10.2. Already prescribed a TCA for the treatment of depression 10.3. Previous myocardial infarction 10.4. Recorded arrhythmias, particularly heart block of any degree, prolonged Q-T interval on ECG 10.5. Mania 10.6. Severe liver disease 10.7. Porphyria 10.8. Congestive heart failure 10.9. Coronary artery insufficiency 10.10. Receiving concomitant drugs that prolong the QT interval (e.g. amiodarone, terfenadine, or sotalol) Other cautions to the use of TCAs will not be an exclusion, but these will be recorded at screening and clarified with the patient’s GP and the lead GP in each hub prior to study entry.
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Global symptoms of IBS measured using the IBS Severity Scoring System (IBS-SSS) at 6 months | — |
Secondary
| Measure | Time frame |
|---|---|
| 1. Relief of IBS symptoms measured using the Subjective Global Assessment (SGA) of relief of IBS symptoms at 3, 6 and 12 months 2. Relief of IBS symptoms measured via a binary response to the question: “Have you had adequate relief of your IBS symptoms?” asked electronically, or via a paper-based diary, weekly until 6 months. 3. Anxiety measured using the Hospital Anxiety and Depression Scale (HADS – anxiety score) at 3, 6 and 12 months 4. Depression measured using the Hospital Anxiety and Depression Scale (HADS – depression score) at 3, 6 and 12 months 5. Healthcare use, use of other medications for IBS, and need for referral to secondary care, self-reported by the participant via a resource use questionnaire using a 3-month recall period (6-month recall period at 12 months). This will collect data concerning all resource use and medications in the community, and in primary and secondary care. Private costs and days off work related to IBS will also be collected. This will be assessed at 3, 6 and 12 months. 6. Quality-adjusted life years measured using the EQ-5D-3L at 3, 6 and 12 months 7. Ability to work and participate in other activities measured using the Work and Social Adjustment Scale (WSAS) total score at 3, 6 and 12 months 8. IBS-associated somatic symptoms measured using Patient Health Questionnaire 12 (PHQ-12) at 6 months 9. Cost-effectiveness expressed in terms of incremental cost per Quality Adjusted Life Year (QALY) at 6 and 12 months 10. Tolerability measured using the Antidepressant Side-Effect Checklist (ASEC) at 3, 6 and 12 months 11. Acceptability of treatment measured by participant self-report, as well as the decision to continue trial medication beyond 6 months. Participants will be asked “On balance do you find this medication acceptable to take and would you want to keep taking it”. This will be assessed at 6 months. 12. Adherence to therapy measured by asking the participants “Since you were last asked, which of the options best describes | — |
Countries
England, United Kingdom
Outcome results
None listed