Management of diarrhoea in ulcerative colitis: multi-arm multi stage trial of low FODMAP diet, amitriptyline, ondansetron, or loperamide: MODULATE.

Phase 1

• Conditions: Diarrhoea in patients with stable ulcerative colitis.; MedDRA version: 20.1Level: LLTClassification code 10045365Term: Ulcerative colitisSystem Organ Class: 100000004856; MedDRA version: 20.1Level: LLTClassification code 10033007Term: Other ulcerative colitisSystem Organ Class: 100000004856; MedDRA version: 20.1Level: LLTClassification code 10066557Term: Chronic diarrhoeaSystem Organ Class: 100000004856; Therapeutic area: Diseases [C] - Digestive System Diseases [C06]

• Registration Number: EUCTR2019-003220-21-GB
• Lead Sponsor: niversity of Leeds

Brief Summary

Not available

Detailed Description

Not available

Study Timeline

• Results First Posted: 1900-01-01
• Study Start: 2019-12-12
• Last Update Posted: 19 October 2020

Recruitment & Eligibility

• Status: Authorised-recruitment may be ongoing or finished
• Sex: All
• Target Recruitment: 491

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. Stable UC at the time of randomisation, in the clinical opinion of the gastroenterologist1,
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 below2:
a.Whether the patient has experienced any thoughts of harming themselves, or ending their life in the last 7-10 days?
b.Whether the patient currently has any thoughts of harming themselves or ending their life?
c.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:
a.post-menopausal (no menses for 12 months without an alternative medical cause), or;
b.surgically sterile (hysterectomy, bilateral salpingectomy or bilateral oophorectomy), or;
c.using highly effective contraception (and must agree to continue for 7 days after the last dose of the investigational medicinal product [IMP]). 3
13.Able to complete questionnaires and trial assessments.
14.Able to provide written informed consent.

Are the trial subjects under 18? no
Number of subjects for this age range: 0
F.1.2 Adults (18-64 years) yes
F.1.2.1 Number of subjects for this age range 417
F.1.3 Elderly (>=65 years) yes
F.1.3.1 Number of subjects for this age range 74

Exclusion Criteria

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 or at randomisation.
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 [30].
8.Known allergy to TCAs, ondansetron, or loperamide.
9.Current use of a TCA at the time of the initial screening telephone call or at randomisation.
10.Previous failed treatment with, or 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.4
12.Contraindications5 to the current use of TCAs including patients with any of the following:
a.taking monoamine oxidase inhibitors, or receiving them within the last 2 weeks;
b.already currently prescribed a TCA for the treatment of depression
c.previous myocardial infarction;
d.recorded arrhythmias, particularly heart block of any degree, or prolonged Q-T interval on electrocardiogram;
e.mania;
f.severe liver disease;
g.porphyria;
h.congestive heart failure;
i.coronary artery insufficiency;
j.receiving concomitant drugs that prolong the QT interval (e.g. amiodarone, terfenadine, or sotalol).
13. Contraindications to the current use of ondansetron, including:
a.concomitant use of apomorphine;
b.concomitant use of other drugs that prolong the QT interval.
14.Contraindications to the current use of loperamide, including:
a.acute UC;
b.acute dysentery, which is characterised by blood in stools and high fever;
c.bacterial enterocolitis caused by invasive organisms;
d.pseudomembranous colitis associated with the use of broad-spectrum antibiotics.
15.Pregnancy, planned pregnancy during the study, pregnancy within 3 months of study completion, or breastfeeding6.

1 A flexible sigmoidoscopy with 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. Rectal bleeding reported by the patient would contribute to the assessment of disease stability and if present should be assessed by flexible sigmoidoscopy.
2Suicidal ideation should be assessed on the screening telephone call. No more than 14 days should elapse between the initial suicidal ideation assessment and study entry/ randomisation. If more than 14 days have elapsed then the suicidal ideation assessment should be repeated.
3Highly effective contraception is defined as one of the following: combined (oestrogen and progestogen-containing) hormonal contraception associated with inhibition of ovulation (oral, intravaginal, or transdermal); progestogen-only hormonal contraception associated with inhibition of ovulation (oral, injectable, or implantable); intrauterine device (IUD); intrauterine hormone-releasing system (IUS); bilateral tubal occlusion; vasectomised partner; practising true abstinence ( defined as refraining from heterosexual intercourse, when this is in line with the preferred and usual lifestyle of the subject).
4Patients currently waiting to see a dietitian for a low FODMAP diet must agree not

Study & Design

• Study Type: Interventional clinical trial of medicinal product
• Study Design: Not specified