Mesalazine Treatment in IBS (The MIBS Study)
This study is currently recruiting participants.
Verified September 2012 by Karolinska Institutet
Sponsor:
Hans Törnblom
Collaborators:
Sahlgrenska University Hospital, Sweden
Smerud Medical Research International AS
Alimenta AB
Tillotts Pharma AG
Karolinska University Hospital
Norrlands University Hospital
Information provided by (Responsible Party):
Hans Törnblom, Karolinska Institutet
ClinicalTrials.gov Identifier:
NCT01699438
First received: September 16, 2012
Last updated: September 30, 2012
Last verified: September 2012
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Purpose
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:
- 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
| Condition | Intervention | Phase |
|---|---|---|
|
Irritable Bowel Syndrome |
Drug: Mesalazine Drug: Placebo |
Phase 2 |
| 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: | Mesalazine Treatment in IBS, a Double-blind Placebo-controlled Phase II Intervention Study in Adult Patients |
Resource links provided by NLM:
Further study details as provided by Karolinska Institutet:
Primary Outcome Measures:
- 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)
Secondary Outcome Measures:
- 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
| Estimated Enrollment: | 200 |
| Study Start Date: | April 2012 |
| Estimated Study Completion Date: | October 2013 |
| Estimated Primary Completion Date: | October 2013 (Final data collection date for primary outcome measure) |
| Arms | Assigned Interventions |
|---|---|
| Experimental: Mesalazine |
Drug: Mesalazine
2400 mg q.d. for 8 weeks
Other Name: Asacol
|
| Placebo Comparator: Placebo |
Drug: Placebo
3 tablets q.d. for 8 weeks
|
Eligibility| Ages Eligible for Study: | 18 Years to 70 Years |
| Genders Eligible for Study: | Both |
| Accepts Healthy Volunteers: | No |
Criteria
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.
Contacts and Locations
Please refer to this study by its ClinicalTrials.gov identifier: NCT01699438
Locations
| Sweden | |
| Sahlgrenska University Hospital | Recruiting |
| Göteborg, Sweden | |
| Contact: Hans Tornblom, MD, PhD +46313429939 hans.tornblom@gu.se | |
| Principal Investigator: Hans Törnblom, MD, PhD | |
| Sub-Investigator: Magnus Simrén, MD, PhD | |
| Karolinska University Hospital | Not yet recruiting |
| Huddinge, Sweden | |
| Contact: Greger Lindberg, MD, PhD +46858580000 greger.lindberg@ki.se | |
| Principal Investigator: Greger Lindberg, MD | |
| Sub-Investigator: Yesuf Taha, MD, PhD | |
| Norrland's University Hospital | Not yet recruiting |
| Umeå, Sweden | |
| Contact: Pontus Karling, MD, PhD +46907850000 pontus.karling@vll.se | |
| Principal Investigator: Pontus Karling, MD | |
Sponsors and Collaborators
Hans Törnblom
Sahlgrenska University Hospital, Sweden
Smerud Medical Research International AS
Alimenta AB
Tillotts Pharma AG
Karolinska University Hospital
Norrlands University Hospital
Investigators
| Principal Investigator: | Hans Törnblom, MD, PhD | Sahlgrenska University Hospital, Sweden |
More Information
No publications provided
| Responsible Party: | Hans Törnblom, MD, PhD, Karolinska Institutet |
| ClinicalTrials.gov Identifier: | NCT01699438 History of Changes |
| Other Study ID Numbers: | SMR-2268 |
| Study First Received: | September 16, 2012 |
| Last Updated: | September 30, 2012 |
| Health Authority: | Sweden: Medical Products Agency |
Keywords provided by Karolinska Institutet:
|
Irritable Bowel Syndrome Inflammation Mesalazine |
Additional relevant MeSH terms:
|
Irritable Bowel Syndrome 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 May 22, 2013