Amitriptyline at low-dose and titrated for irritable bowel syndrome as second-line treatment

Recruitment & Eligibility

Status: Completed

Sex: All

Target Recruitment: 463

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

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.

Study & Design

Study Type: Interventional

Study Design: Not specified

Primary Outcome Measures

Name	Time	Method
Global symptoms of IBS measured using the IBS Severity Scoring System (IBS-SSS) at 6 months

Secondary Outcome Measures

Name	Time	Method

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