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

Efficacy and Mode of Action of Mesalazine in the Treatment of Diarrhoea-predominant Irritable Bowel Syndrome (IBS-D).

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.

Study Overview

• Status: Completed
• Conditions: Irritable Bowel Syndrome With Diarrhoea
• Intervention / Treatment: Drug: Mesalazine; Drug: Placebo

• Study Type: Interventional
• Enrollment (Actual): 108
• Phase: Phase 4

Contacts and Locations

Study Locations

• United Kingdom
  • Notts
    • Nottingham, Notts, United Kingdom, NG7 2UH
      • Queen's Medical Centre

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 75 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

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 Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Quadruple

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Mesalazine Granules; 2g oral granules, once a day for 1 week, then 2g oral granules, twice a day for 11 weeks	Drug: Mesalazine; 2g oral granules, once a day for 1 week, then 2g oral granules, twice a day for 11 weeks
Placebo Comparator: Placebo Granules; 2g oral granules, once a day for 1 week, then 2g oral granules, twice a day for 11 weeks	Drug: Placebo; 2g oral granules, once a day for 1 week, then 2g oral granules, twice a day for 11 weeks

What is the study measuring?

Primary Outcome Measures

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

Secondary Outcome Measures

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

Collaborators and Investigators

• Sponsor: University of Nottingham
• Collaborators: National Institute for Health Research, United Kingdom
• Investigators: Principal Investigator: Robin C Spiller, MD, NIHR Biomedical Research Unit, Nottingham University

Publications and helpful links

General Publications

• Lam C, Tan W, Leighton M, Hastings M, Lingaya M, Falcone Y, Zhou X, Xu L, Whorwell P, Walls AF, Zaitoun A, Montgomery A, Spiller R. A mechanistic multicentre, parallel group, randomised placebo-controlled trial of mesalazine for the treatment of IBS with diarrhoea (IBS-D). Gut. 2016 Jan;65(1):91-9. doi: 10.1136/gutjnl-2015-309122. Epub 2015 Mar 12.

Study record dates

Study Major Dates

• Study Start: March 1, 2011
• Primary Completion (Actual): September 1, 2013
• Study Completion (Actual): September 1, 2013

Study Registration Dates

• First Submitted: September 21, 2010
• First Submitted That Met QC Criteria: March 15, 2011
• First Posted (Estimate): March 16, 2011

Study Record Updates

• Last Update Posted (Estimate): January 17, 2014
• Last Update Submitted That Met QC Criteria: January 16, 2014
• Last Verified: January 1, 2014

More Information

Terms related to this study

• Keywords: IBS; diarrhoea
• Additional Relevant MeSH Terms: Digestive System Diseases; Pathologic Processes; Disease; Signs and Symptoms, Digestive; Gastrointestinal Diseases; Colonic Diseases, Functional; Colonic Diseases; Intestinal Diseases; Syndrome; Irritable Bowel Syndrome; Diarrhea; Physiological Effects of Drugs; Peripheral Nervous System Agents; Analgesics; Sensory System Agents; Anti-Inflammatory Agents, Non-Steroidal; Analgesics, Non-Narcotic; Anti-Inflammatory Agents; Antirheumatic Agents; Mesalamine
• Other Study ID Numbers: 10085 (DAIDS ES)