Mesalazine Treatment in IBS (The MIBS Study) (MIBS)

February 23, 2017 updated by: Hans Törnblom

Mesalazine Treatment in IBS, a Double-blind Placebo-controlled Phase II Intervention Study in Adult Patients

Irritable bowel syndrome (IBS) is a condition characterised by abdominal pain or discomfort in combination with altered bowel function (stool frequency and/or stool consistency), currently defined by the Rome III criteria. The current IBS definition specifies that there are no structural or biochemical abnormalities to account for the symptoms but there is growing evidence that in at least a subset of IBS patients, a discrete immune activation might be a key pathogenetic factor. The condition is prone to develop after a gastroenteritis, post-infectious IBS, and increased numbers of lymphocytes, mast cells and pro-inflammatory cytokines like Interleukin (IL)-1β, IL-6, Tumor necrosis factor (TNF)-α and a general increase in mucosal cellularity have been reported. Despite this, the efficacy of anti-inflammatory agents has been poorly investigated.

This will be a randomised, double blind, placebo-controlled, parallel-group, multi-centre study that aims to include a total of 200 subjects with irritable bowel syndrome (IBS). All subjects will be randomised to receive either 3x800 mg of mesalazine (Asacol®) or corresponding placebo once daily for a total treatment duration of 8 weeks. Males and females aged 18 to 70 years who already are diagnosed with IBS based on the Rome III diagnostic criteria and with a symptom intensity of at least moderate level; defined as an IBS Severity Scoring System (IBS-SSS) score of ≥175 at both Screening (Visit 1, Day -21±2) and Baseline (Visit 2, Day 0) will be eligible to enter the study.

Primary aim:

To assess the effect of mesalazine (Asacol®) treatment compared to placebo on global IBS symptoms: A treatment responder will be defined by answering the satisfactory relief of IBS-symptoms question "yes" at the end of at least 4 out of of 8 treatment weeks.

Secondary aims:

To assess mesalazine (Asacol®) treatment compared to placebo regarding:

  1. Levels of inflammatory mediators in the rectal mucosa (e.g. neutrophil mediators, eosinophilic mediators, mast cell activity mediators and cytokines) measured by a new diagnostic tool, the Mucosal Patch Technology (MPT) by means of Enzyme-Linked Immunosorbent Assays (ELISA)
  2. Effects on number of immune cells (count per high power field) and cytokine content (immunohistochemistry) in mucosal biopsies
  3. Calprotectin levels in faeces (mg/kg)
  4. Individual IBS symptom parameters derived from a symptom diary and also measured by IBS-SSS

Study Overview

Status

Completed

Conditions

Intervention / Treatment

Study Type

Interventional

Enrollment (Actual)

211

Phase

  • Phase 2

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Locations

  • Sweden
      • Göteborg, Sweden
        • Sahlgrenska University Hospital
      • Huddinge, Sweden
        • Karolinska University Hospital
      • Umeå, Sweden
        • Norrland's University Hospital

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

18 years to 70 years (ADULT, OLDER_ADULT)

Accepts Healthy Volunteers

No

Genders Eligible for Study

All

Description

Inclusion Criteria:

  • Males and females aged 18 to 70 years, both inclusive
  • Subject is diagnosed with irritable bowel syndrome (IBS) prior to Screening based on the Rome III diagnostic criteria.
  • Subject presents with IBS symptom intensity of at least moderate level; defined as an IBS Severity Scoring System (IBS-SSS) score of ≥175 at both Screening (Visit 1, Day -21±2) and Baseline (Visit 2, Day 0)
  • Provision of signed informed consent

Exclusion Criteria:

  • Subjects who are unable to understand the written and verbal instructions
  • Presence of a systemic inflammatory disease
  • Presence of other gastrointestinal diseases likely to explain the IBS symptoms
  • Presence of other severe somatic disease
  • Treatment with non-steroidal anti-inflammatory drugs (NSAID), opioid analgetics or acetylsalicylic acid (ASA) compounds within 7 days prior to screening (Visit 1, Day -21±2)
  • Treatment with systemic antibiotics within 28 days prior to Screening (Visit 1, Day -21±2)
  • Treatment with immunosuppressant drugs within 28 days prior to Screening (Visit 1, Day -21±2)
  • Other significant medical treatment, which, in the opinion of the investigator, may compromise the safety and efficacy objectives of the study, within 28 days prior to Screening (Visit 1, Day -21±2)
  • Previously confirmed allergy towards ASA or mesalazine
  • Presence of renal disease and/or concomitant treatment with medications with potential renal side effects
  • Current ongoing infection
  • History of, or current, drug or alcohol dependence
  • Pregnant or lactating women
  • Subjects suspected not to follow instructions based on the discretion of the Investigator
  • Current participation in other intervention studies
  • Female subjects of childbearing potential unwilling to use adequate contraceptive measures throughout the duration of the study.

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: TREATMENT
  • Allocation: RANDOMIZED
  • Interventional Model: PARALLEL
  • Masking: QUADRUPLE

Arms and Interventions

Participant Group / Arm
Intervention / Treatment
PLACEBO_COMPARATOR: Placebo
Drug: Placebo
3 tablets q.d. for 8 weeks
EXPERIMENTAL: Mesalazine
Drug: Mesalazine
2400 mg q.d. for 8 weeks
Other Names:
  • Asacol

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Global Irritable Bowel Syndrome (IBS) symptoms
Time Frame: 8 weeks
The main measurement parameter of symptom alleviation will be a weekly question regarding satisfactory relief of global IBS symptoms. A treatment responder will be defined as answering "yes" ≥50% of the weeks (≥4 weeks)
8 weeks

Secondary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Inflammatory mediators
Time Frame: 8 weeks
Measured by the Mucosal Patch Technology (MPT), e.g. neutrophil mediators (myeloperoxidase (MPO)), eosinophilic mediators (eosinophil cationic protein (ECP)), mast cell activity mediators (tryptase) and cytokines (Interleukin (IL)-2, IL-6, Tumor necrosis factor (TNF)-alpha, IL-1beta etc) by Enzyme-Linked Immunosorbent Assays (ELISA), (ug/ml).
8 weeks
Effect on immune cells and cytokines in mucosal biopsies
Time Frame: 8 weeks
Counts per high-power field in microscopy and by immunohistochemistry
8 weeks
Levels of calprotectin in faeces
Time Frame: 8 weeks
Enzyme-Linked Immunosorbent Assay (ELISA), mg/kg
8 weeks
Change in total IBS symptom severity score (IBS-SSS)
Time Frame: 8 weeks
Absolute change in IBS-SSS compared to baseline.
8 weeks
Individual symptom parameters in IBS symptom severity score (IBS-SSS) and the IBS diary
Time Frame: 8 weeks
Reduction of scores regarding individual question components (visual analog scale (VAS)) in IBS-SSS. Stool frequency and consistency expressed by Bristol Stool Form Scale in a separate IBS diary.
8 weeks
Exploratory responder variables
Time Frame: 8 weeks
  1. Satisfactory symptom relief ≥75% of the time
  2. Reduction in IBS-SSS ≥50 at end of treatment compared to baseline
8 weeks

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

Hans Törnblom

Collaborators

Karolinska University Hospital
Oslo University Hospital
Sahlgrenska University Hospital, Sweden
Haukeland University Hospital
Sykehuset Innlandet HF
Tillotts Pharma AG
Smerud Medical Research International AS
Alimenta AB

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start (ACTUAL)

April 1, 2012

Primary Completion (ACTUAL)

December 1, 2016

Study Completion (ACTUAL)

February 1, 2017

Study Registration Dates

First Submitted

September 16, 2012

First Submitted That Met QC Criteria

September 30, 2012

First Posted (ESTIMATE)

October 3, 2012

Study Record Updates

Last Update Posted (ACTUAL)

February 24, 2017

Last Update Submitted That Met QC Criteria

February 23, 2017

Last Verified

February 1, 2017

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

  • SMR-2268

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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