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

This study has been completed.
Sponsor:
Collaborator:
National Institute for Health Research, United Kingdom
Information provided by (Responsible Party):
University of Nottingham
ClinicalTrials.gov Identifier:
NCT01316718
First received: September 21, 2010
Last updated: January 16, 2014
Last verified: January 2014
  Purpose

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.


Condition Intervention Phase
Irritable Bowel Syndrome With Diarrhoea
Drug: Mesalazine
Drug: Placebo
Phase 4

Study Type: Interventional
Study Design: Allocation: Randomized
Endpoint Classification: Efficacy Study
Intervention Model: Parallel Assignment
Masking: Double Blind (Subject, Caregiver, Investigator, Outcomes Assessor)
Primary Purpose: Treatment
Official Title: Efficacy and Mode of Action of Mesalazine in the Treatment of Diarrhoea-predominant Irritable Bowel Syndrome (IBS-D).

Resource links provided by NLM:


Further study details as provided by University of Nottingham:

Primary Outcome Measures:
  • Change from baseline in average stool frequency during weeks 11 and 12. [ Time Frame: Week 0 and week 12 ] [ Designated as safety issue: No ]
    Clinical Endpoint

  • Change from baseline of number of mast cell per mm2 at week 12 [ Time Frame: Week 0 and week 12 ] [ Designated as safety issue: No ]
    Mechanistic endpoint


Secondary Outcome Measures:
  • Average daily severity of abdominal pain on a 0-10 scale [ Time Frame: Week 0 to week 12 ] [ Designated as safety issue: No ]
    Clinical Endpoint

  • Days with urgency [ Time Frame: weeks 11-12 ] [ Designated as safety issue: No ]
    Clinical Endpoint

  • Mean stool consistency using Bristol Stool Form Score [ Time Frame: Week 0 to week 12 ] [ Designated as safety issue: No ]
    Clinical Endpoint

  • Global satisfaction with control of IBS symptoms [ Time Frame: Week 0 to week 12 ] [ Designated as safety issue: No ]
    as assessed from the answer to the question "Have you had satisfactory relief of your IBS symptoms this week? Yes / No. "

  • Mast cell tryptase release during 6 hour biopsy incubation [ Time Frame: Week 0 and week 12 ] [ Designated as safety issue: No ]
    Mechanistic endpoint

  • IL-1β, TNF-a, histamine and serotonin secretion during same incubation [ Time Frame: Week 0 and week 12 ] [ Designated as safety issue: No ]
    Mechanistic endpoint

  • Small bowel tone assessed by volume of fasting small bowel water [ Time Frame: Week 0 and week 12 ] [ Designated as safety issue: No ]
    Mechanistic endpoint

  • Euro-Qol Score [ Time Frame: Week 0 and week 12 ] [ Designated as safety issue: No ]
    Ancillary endpoint

  • Centres for disease control and prevention health related quality of life healthy days core module score [ Time Frame: Week 0 and week 12 ] [ Designated as safety issue: No ]
    Ancillary endpoint

  • Hospital Anxiety Depression Scale Score [ Time Frame: Week 0 and week 12 ] [ Designated as safety issue: No ]
    Ancillary endpoint

  • Patient Health Questionnaire -15 [ Time Frame: Week 0 and week 12 ] [ Designated as safety issue: No ]
    Ancillary endpoint


Enrollment: 108
Study Start Date: March 2011
Study Completion Date: September 2013
Primary Completion Date: September 2013 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
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

  Eligibility

Ages Eligible for Study:   18 Years to 75 Years
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

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.
  Contacts and Locations
Please refer to this study by its ClinicalTrials.gov identifier: NCT01316718

Locations
United Kingdom
Queen's Medical Centre
Nottingham, Notts, United Kingdom, NG7 2UH
Sponsors and Collaborators
University of Nottingham
National Institute for Health Research, United Kingdom
Investigators
Principal Investigator: Robin C Spiller, MD NIHR Biomedical Research Unit, Nottingham University
  More Information

No publications provided

Responsible Party: University of Nottingham
ClinicalTrials.gov Identifier: NCT01316718     History of Changes
Other Study ID Numbers: 10085
Study First Received: September 21, 2010
Last Updated: January 16, 2014
Health Authority: United Kingdom: Medicines and Healthcare Products Regulatory Agency
United Kingdom: National Health Service
United Kingdom: National Institute for Health Research
United Kingdom: Research Ethics Committee

Keywords provided by University of Nottingham:
IBS
diarrhoea

Additional relevant MeSH terms:
Diarrhea
Irritable Bowel Syndrome
Signs and Symptoms, Digestive
Signs and Symptoms
Colonic Diseases, Functional
Colonic Diseases
Intestinal Diseases
Gastrointestinal Diseases
Digestive System Diseases
Mesalamine
Anti-Inflammatory Agents, Non-Steroidal
Analgesics, Non-Narcotic
Analgesics
Sensory System Agents
Peripheral Nervous System Agents
Physiological Effects of Drugs
Pharmacologic Actions
Anti-Inflammatory Agents
Therapeutic Uses
Antirheumatic Agents
Central Nervous System Agents

ClinicalTrials.gov processed this record on April 23, 2014