Mesalazine Treatment in IBS (The MIBS Study)
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.
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.
To assess mesalazine (Asacol®) treatment compared to placebo regarding:
- 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)
- Effects on number of immune cells (count per high power field) and cytokine content (immunohistochemistry) in mucosal biopsies
- Calprotectin levels in faeces (mg/kg)
- Individual IBS symptom parameters derived from a symptom diary and also measured by IBS-SSS
|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:||Mesalazine Treatment in IBS, a Double-blind Placebo-controlled Phase II Intervention Study in Adult Patients|
- Global Irritable Bowel Syndrome (IBS) symptoms [ Time Frame: 8 weeks ] [ Designated as safety issue: No ]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)
- Inflammatory mediators [ Time Frame: 8 weeks ] [ Designated as safety issue: No ]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).
- Effect on immune cells and cytokines in mucosal biopsies [ Time Frame: 8 weeks ] [ Designated as safety issue: No ]Counts per high-power field in microscopy and by immunohistochemistry
- Levels of calprotectin in faeces [ Time Frame: 8 weeks ] [ Designated as safety issue: No ]Enzyme-Linked Immunosorbent Assay (ELISA), mg/kg
- Change in total IBS symptom severity score (IBS-SSS) [ Time Frame: 8 weeks ] [ Designated as safety issue: No ]Absolute change in IBS-SSS compared to baseline.
- Individual symptom parameters in IBS symptom severity score (IBS-SSS) and the IBS diary [ Time Frame: 8 weeks ] [ Designated as safety issue: No ]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.
- Exploratory responder variables [ Time Frame: 8 weeks ] [ Designated as safety issue: No ]
- Satisfactory symptom relief ≥75% of the time
- Reduction in IBS-SSS ≥50 at end of treatment compared to baseline
|Study Start Date:||April 2012|
|Estimated Study Completion Date:||December 2015|
|Estimated Primary Completion Date:||September 2015 (Final data collection date for primary outcome measure)|
2400 mg q.d. for 8 weeks
Other Name: Asacol
|Placebo Comparator: Placebo||
3 tablets q.d. for 8 weeks
Please refer to this study by its ClinicalTrials.gov identifier: NCT01699438
|Sahlgrenska University Hospital||Recruiting|
|Contact: Hans Tornblom, MD, PhD +46313429939 firstname.lastname@example.org|
|Principal Investigator: Hans Törnblom, MD, PhD|
|Sub-Investigator: Magnus Simrén, MD, PhD|
|Karolinska University Hospital||Not yet recruiting|
|Contact: Greger Lindberg, MD, PhD +46858580000 email@example.com|
|Principal Investigator: Greger Lindberg, MD|
|Sub-Investigator: Yesuf Taha, MD, PhD|
|Norrland's University Hospital||Not yet recruiting|
|Contact: Pontus Karling, MD, PhD +46907850000 firstname.lastname@example.org|
|Principal Investigator: Pontus Karling, MD|
|Principal Investigator:||Hans Törnblom, MD, PhD||Sahlgrenska University Hospital, Sweden|