MODULATE: a study to evaluate the effectiveness of either amitriptyline, ondansetron, loperamide, or dietary intervention (the low FODMAP diet) against standard dietary advice for the treatment of diarrhoea in patients with stable ulcerative colitis
- Conditions
- lcerative colitisDigestive SystemUlcerative colitis
- Registration Number
- ISRCTN16086699
- Lead Sponsor
- niversity of Leeds
- Brief Summary
Not available
- Detailed Description
Not available
Recruitment & Eligibility
- Status
- Stopped
- Sex
- All
- Target Recruitment
- 491
Current inclusion criteria as of 02/02/2024:
1. A histological diagnosis of UC in secondary care, including left-sided colitis or extensive colitis
2. Age > = 18 years
3. At least moderate discomfort from diarrhoea according to the GSRS-IBS [26] (equating to a score of > = 4 on the diarrhoea subscale of the GSRS-IBS)
4. On stable doses of UC-related medication for > = 2 months at time of initial screening telephone call
5. Ongoing diarrhoea for 3 months prior to initial screening telephone call
6. A CRP < = 5mg/L (measured as per local practise) within 4 weeks prior to randomisation
7. FC < 250mcg/g [29] within 4 weeks prior to randomisation
8. Stable UC at the time of randomisation, in the clinical opinion of the gastroenterologist (a flexible sigmoidoscopy with a Mayo score =1 is only required if there is clinical uncertainty regarding the stability of the patient’s UC and is at the discretion of the treating physician)
9. No evidence of active suicidal ideation at time of initial screening telephone call and prior to randomisation, as determined by the three clinical screening questions:
9.1. Whether the patient has experienced any thoughts of harming themselves, or ending their life in the last 7-10 days?
9.2. Whether the patient currently has any thoughts of harming themselves or ending their life?
9.3. Whether the patient has any active plans or ideas about harming themselves, or taking their life, in the near future?
10. No recent history of self-reported self-harm (an episode of self-harm within the last 12 months)
11. Willing to be considered for all treatment arms of the trial, and to remain in the treatment arm to which they are assigned
12. If female must be:
12.1. Post-menopausal (no menses for 12 months without an alternative medical cause), or;
12.2. Surgically sterile (hysterectomy, bilateral salpingectomy or bilateral oophorectomy), or;
12.3. Using highly effective contraception (and must agree to continue for 7 days after the last dose of the investigational medicinal product [IMP])
13. Able to complete questionnaires and trial assessments
14. Able to provide written informed consent
Previous inclusion criteria:
1. A histological diagnosis of UC in secondary care, including left-sided colitis or extensive colitis
2. Age > = 18 years
3. At least moderate discomfort from diarrhoea according to the GSRS-IBS [26] (equating to a score of > = 4 on the diarrhoea subscale of the GSRS-IBS)
4. On stable doses of UC-related medication for > = 2 months at time of initial screening telephone call
5. Ongoing diarrhoea for 3 months prior to initial screening telephone call
6. A CRP < = 5mg/L (measured as per local practise) within 4 weeks prior to randomisation
7. FC < 250mcg/g [29] within 4 weeks prior to randomisation
8. Mayo score of < = 1 at flexible sigmoidoscopy within the past 3 months prior to initial screening telephone call
9. No evidence of active suicidal ideation at time of initial screening telephone call and prior to randomisation, as determined by the three clinical screening questions:
9.1. Whether the patient has experienced any thoughts of harming themselves, or ending their life in the last 7-10 days?
9.2. Whether the patient currently has any thoughts of harming themselves or ending their life?
9.3. Whether the patient has any active plans or ideas about harming themselves, or taking their life, in the near future?
10. No recent history of self-reported self-harm (an episode of self-harm within the last 12 mo
Current exclusion criteria as of 02/02/2024:
1. Inflammatory bowel disease unclassifiable or Crohn’s disease
2. Ulcerative proctitis
3. Body mass index =18.5 kg/m2.
4. Previous or planned gastrointestinal IBD-related resectional surgery or previous cholecystectomy
5. Having received steroids for UC within the last 2 months prior to the initial screening telephone call
6. Coeliac disease (as confirmed via anti-tissue transglutaminase (tTG) antibodies)
7. A previous diagnosis of colorectal dysplasia or cancer, or no up to date surveillance colonoscopy, as per current British Society of Gastroenterology guidelines
8. Known allergy to TCAs, ondansetron, or loperamide.
9. Current use of a TCA at time of initial screening telephone call.
10. Previous failed treatment with regular use of amitriptyline, ondansetron, or loperamide for diarrhoea.
11. Currently on, or have previously tried and failed, a low FODMAP diet under dietitian guidance.3
12. Contraindications to the current use of TCAs including patients with any of the following:
12.1. Taking monoamine oxidase inhibitors, or receiving them within the last 2 weeks;
12.2. Already currently prescribed a TCA for the treatment of depression
12.3 Previous myocardial infarction;
12.4. Recorded arrhythmias, particularly heart block of any degree, or prolonged Q-T interval on electrocardiogram;
12.5. Mania;
12.6. Severe liver disease;
12.7. Porphyria;
12.8. Congestive heart failure;
12.9. Coronary artery insufficiency;
12.10 Receiving concomitant drugs that prolong the QT interval (e.g. amiodarone, terfenadine, or sotalol)
13. Contraindications to the current use of ondansetron, including:
13.1. Concomitant use of apomorphine;
13.2. Concomitant use of other drugs that prolong the QT interval.
14. Contraindications to the current use of loperamide, including:
14.1. Acute UC;
14.2. Acute dysentery, which is characterised by blood in stools and high fever;
14.3. Bacterial enterocolitis caused by invasive organisms;
14.4. Pseudomembranous colitis associated with the use of broad-spectrum antibiotics
15. Pregnancy, planned pregnancy within 3 months of study completion, or breastfeeding
Previous exclusion criteria:
1. Inflammatory bowel disease unclassifiable or Crohn’s disease
2. Ulcerative proctitis
3. Previous or planned gastrointestinal IBD-related resectional surgery or previous cholecystectomy
4. Having received steroids for UC within the last 2 months prior to the initial screening telephone call
5. Coeliac disease (as confirmed via anti-tissue transglutaminase (tTG) antibodies)
6. A previous diagnosis of colorectal dysplasia or cancer, or no up to date surveillance colonoscopy, as per current British Society of Gastroenterology guidelines
7. Known allergy to TCAs, ondansetron, or loperamide.
8. Current use of a TCA at time of initial screening telephone call.
9. Previous failed treatment with regular use of amitriptyline, ondansetron, or loperamide for diarrhoea.
10. Currently on, or have previously tried and failed, a low FODMAP diet under dietitian guidance.3
11. Contraindications to the current use of TCAs including patients with any of the following:
11.1. Taking monoamine oxidase inhibitors, or receiving them within the last 2 weeks;
11.2. Already currently prescribed a TCA for the treatment of depression
11.3 Previous myocardial infarction;
11.4. Recorded arrhythmias, particularly heart block of any degree, or prolonged Q-T interval on electrocardiogram;
11.5. Mania;
11.6. Severe liv
Study & Design
- Study Type
- Interventional
- Study Design
- Not specified
- Primary Outcome Measures
Name Time Method
- Secondary Outcome Measures
Name Time Method