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Mesalazine Treatment in IBS (The MIBS Study)

This study is currently recruiting participants. (see Contacts and Locations)
Verified November 2014 by Göteborg University
Sponsor:
Collaborators:
Sahlgrenska University Hospital, Sweden
Smerud Medical Research International AS
Alimenta AB
Tillotts Pharma AG
Karolinska University Hospital
Haukeland University Hospital
Oslo University Hospital
Sykehuset Innlandet HF
Information provided by (Responsible Party):
Hans Törnblom, Göteborg University
ClinicalTrials.gov Identifier:
NCT01699438
First received: September 16, 2012
Last updated: November 6, 2014
Last verified: November 2014
  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:

  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

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 Göteborg University:

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 ]
    1. Satisfactory symptom relief ≥75% of the time
    2. Reduction in IBS-SSS ≥50 at end of treatment compared to baseline


Estimated Enrollment: 200
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)
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
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

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
Haukeland University Hospital
Oslo University Hospital
Sykehuset Innlandet HF
Investigators
Principal Investigator: Hans Törnblom, MD, PhD Sahlgrenska University Hospital, Sweden
  More Information

No publications provided

Responsible Party: Hans Törnblom, MD, PhD, Göteborg University
ClinicalTrials.gov Identifier: NCT01699438     History of Changes
Other Study ID Numbers: SMR-2268
Study First Received: September 16, 2012
Last Updated: November 6, 2014
Health Authority: Sweden: Medical Products Agency

Keywords provided by Göteborg University:
Irritable Bowel Syndrome
Inflammation
Mesalazine

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

ClinicalTrials.gov processed this record on November 20, 2014