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

NCT01316718 | Completed Phase 4 DMC

• 1 other identifier: 10085
• Study Type: interventional
• Target: 108
• Locations: 1 country
• Sites: 1

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.

Conditions

Irritable Bowel Syndrome With Diarrhoea

Keywords

IBS; diarrhoea

Outcome Measures

Primary Outcomes (2)

• 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 Outcomes (11)

• Average daily severity of abdominal pain on a 0-10 scale

  Week 0 to week 12

• Days with urgency

  weeks 11-12

• Mean stool consistency using Bristol Stool Form Score

  Week 0 to week 12

• Global satisfaction with control of IBS symptoms

  Week 0 to week 12

• Mast cell tryptase release during 6 hour biopsy incubation

  Week 0 and week 12

Study Arms (2)

Mesalazine Granules

EXPERIMENTAL

2g oral granules, once a day for 1 week, then 2g oral granules, twice a day for 11 weeks

Drug: Mesalazine

Placebo Granules

PLACEBO COMPARATOR

2g oral granules, once a day for 1 week, then 2g oral granules, twice a day for 11 weeks

Drug: Placebo

Interventions

Mesalazine DRUG

2g oral granules, once a day for 1 week, then 2g oral granules, twice a day for 11 weeks

Mesalazine Granules

Placebo DRUG

2g oral granules, once a day for 1 week, then 2g oral granules, twice a day for 11 weeks

Placebo Granules

Eligibility Criteria

• Age: 18 Years - 75 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Male or Female patients aged 18-75 years old able to give informed consent.
• 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).
• IBS-D Patients meeting Rome III criteria prior to screening phase.
• 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\*.
• Patients with a stool frequency of 3 or more per day for 2 or more days per week during the screening phase\*.
• Satisfactory completion of the daily stool and symptom diary during the screening phase at the discretion of the investigator.
• 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.

You may not qualify if:

• Women who are pregnant or breast feeding
• 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.
• 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.
• Patients with other gastro-intestinal diseases including colitis and Crohn's disease.
• Patients with the following conditions: Renal impairment, severe hepatic impairment or salicylate hypersensitivity.
• Patients currently participating in another trial or have been in a trial within the previous 3 months
• Patients who in the opinion of the investigator are considered unsuitable due to inability to comply with instructions
• 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.

Sponsors & Collaborators

• University of Nottingham: lead
• National Institute for Health Research, United Kingdom: collaborator

Study Sites (1)

Queen's Medical Centre

Nottingham, Notts, NG7 2UH, United Kingdom

Location

Related Publications (1)

• 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.

  PMID: 25765462 DERIVED

MeSH Terms

Conditions

Diarrhea

Interventions

Mesalamine

Condition Hierarchy (Ancestors)

Signs and Symptoms, Digestive; Signs and Symptoms; Pathological Conditions, Signs and Symptoms

Intervention Hierarchy (Ancestors)

meta-Aminobenzoates; Aminobenzoates; Benzoates; Acids, Carbocyclic; Carboxylic Acids; Organic Chemicals; Aminosalicylic Acids; Salicylates; Hydroxybenzoates; Hydroxy Acids; Benzene Derivatives; Hydrocarbons, Aromatic; Hydrocarbons, Cyclic; Hydrocarbons; Phenols

Study Officials

• Robin C Spiller, MD

  NIHR Biomedical Research Unit, Nottingham University

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 4
• Allocation: RANDOMIZED
• Masking: QUADRUPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR, OUTCOMES ASSESSOR
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: September 21, 2010
• First Posted: March 16, 2011
• Study Start: March 1, 2011
• Primary Completion: September 1, 2013
• Study Completion: September 1, 2013
• Last Updated: January 17, 2014

Record last verified: 2014-01

Locations

GB (1)