Mesalazine for the Treatment of Diarrhoea-predominant Irritable Bowel Syndrome (IBS-D)

Phase 4

Completed

• Conditions: Irritable Bowel Syndrome With Diarrhoea
• Interventions: Drug: Placebo; Drug: Mesalazine

• Registration Number: NCT01316718
• Lead Sponsor: University of Nottingham

Brief Summary

The purpose of the trial is to define the clinical benefit and possible mediators of the benefit of mesalazine in Irritable Bowel Syndrome (IBS) with diarrhoea.

The investigators will therefore evaluate symptoms (primarily bowel frequency) and markers reflecting mast cell activation and small bowel tone.

Detailed Description

Not available

Study Timeline

• Study First Submitted: 2010-09-21
• Study Start: 2011-03
• Study First Submitted QC: 2011-03-15
• Study First Posted: 2011-03-16
• Primary Completion: 2013-09
• Study Completion: 2013-09
• Status Verified: 2014-01
• Last Update Submitted: 2014-01-16
• Last Update Posted: 2014-01-17

Recruitment & Eligibility

• Status: COMPLETED
• Sex: All
• Target Recruitment: 108

Inclusion Criteria

1. Male or Female patients aged 18-75 years old able to give informed consent.

2. Patients should all have had a colonoscopy or a sigmoidoscopy within the last 12 months to exclude microscopic colitis. (If not, but they have had a negative colonoscopy within 5 years and symptoms are unchanged, then a sigmoidoscopy and mucosal biopsy of the left colon would be sufficient to exclude microscopic colitis).

3. IBS-D Patients meeting Rome III criteria prior to screening phase.

4. Patients with ≥ 25% soft (score > 4) and < 25% hard (score 1 or 2) stools during the screening phase, as scored by the daily symptom and stool diary*.

5. Patients with a stool frequency of 3 or more per day for 2 or more days per week during the screening phase*.

6. Satisfactory completion of the daily stool and symptom diary during the screening phase at the discretion of the investigator.

7. Women of child bearing potential willing or able to use at least one highly effective contraceptive method throughout the study. In the context of this study, an effective method is defined as those which result in low failure rate (i.e. less than 1% per year) when used consistently and correctly such as: implants, injectables, combined oral contraceptives, sexual abstinence or vasectomised partner.

   • If inclusion criterion 4 and/or 5 is/are not met but the results are considered atypical (as observed from medical history and patient recall) then the patient can be re-screen on 1 occasion only.

Exclusion Criteria

1. Women who are pregnant or breast feeding

2. Prior abdominal surgery which may cause bowel symptoms similar to IBS (note appendectomy and cholecystectomy will not be an exclusion)

3. Patients unable to stop anti-muscarinics, anti-spasmodics, high dose tricyclic antidepressants (i.e. above 50 mg/day), opiates/anti-diarrhoeal drugs*, NSAIDs (occasional over the counter use and topical formulations are allowed), long-term antibiotics, other anti-inflammatory drugs or 5-ASA containing drugs.

4. Patients on selective serotonin re-uptake inhibitors and low dose tricyclic antidepressants (i.e. up to 50 mg/day) for at least 3 months previous unwilling to remain on a stable dose for the duration of the trial.

5. Patients with other gastro-intestinal diseases including colitis and Crohn's disease.

6. Patients with the following conditions: Renal impairment, severe hepatic impairment or salicylate hypersensitivity.

7. Patients currently participating in another trial or have been in a trial within the previous 3 months

8. Patients who in the opinion of the investigator are considered unsuitable due to inability to comply with instructions

9. Patients with serious concomitant diseases e.g. cardiovascular, respiratory, neurological etc.

   • Loperamide is allowed as rescue medication through-out the trial, however if > 2 doses / week are taken during the screening phase then they are not eligible, though they can be re-screened on 1 occasion only.

Study & Design

• Study Type: INTERVENTIONAL
• Study Design: PARALLEL

Arm && Interventions

Group	Intervention	Description
Placebo Granules	Placebo	2g oral granules, once a day for 1 week, then 2g oral granules, twice a day for 11 weeks
Mesalazine Granules	Mesalazine	2g oral granules, once a day for 1 week, then 2g oral granules, twice a day for 11 weeks

Primary Outcome Measures

Name	Time	Method
Change from baseline of number of mast cell per mm2 at week 12	Week 0 and week 12	Mechanistic endpoint
Change from baseline in average stool frequency during weeks 11 and 12.	Week 0 and week 12	Clinical Endpoint

Secondary Outcome Measures

Name	Time	Method
Average daily severity of abdominal pain on a 0-10 scale	Week 0 to week 12	Clinical Endpoint
Days with urgency	weeks 11-12	Clinical Endpoint
Mean stool consistency using Bristol Stool Form Score	Week 0 to week 12	Clinical Endpoint
Mast cell tryptase release during 6 hour biopsy incubation	Week 0 and week 12	Mechanistic endpoint
IL-1β, TNF-a, histamine and serotonin secretion during same incubation	Week 0 and week 12	Mechanistic endpoint
Small bowel tone assessed by volume of fasting small bowel water	Week 0 and week 12	Mechanistic endpoint
Euro-Qol Score	Week 0 and week 12	Ancillary endpoint
Centres for disease control and prevention health related quality of life healthy days core module score	Week 0 and week 12	Ancillary endpoint
Hospital Anxiety Depression Scale Score	Week 0 and week 12	Ancillary endpoint
Patient Health Questionnaire -15	Week 0 and week 12	Ancillary endpoint
Global satisfaction with control of IBS symptoms	Week 0 to week 12	as assessed from the answer to the question "Have you had satisfactory relief of your IBS symptoms this week? Yes / No. "

Trial Locations

Locations (1)

Queen's Medical Centre; 🇬🇧 Nottingham, Notts, United Kingdom