<clinical_study>
  <!-- This xml conforms to an XML Schema at:
    https://clinicaltrials.gov/ct2/html/images/info/public.xsd -->
  <required_header>
    <download_date>ClinicalTrials.gov processed this data on September 20, 2023</download_date>
    <link_text>Link to the current ClinicalTrials.gov record.</link_text>
    <url>https://clinicaltrials.gov/ct2/show/NCT01699438</url>
  </required_header>
  <id_info>
    <org_study_id>SMR-2268</org_study_id>
    <nct_id>NCT01699438</nct_id>
  </id_info>
  <brief_title>Mesalazine Treatment in IBS (The MIBS Study)</brief_title>
  <acronym>MIBS</acronym>
  <official_title>Mesalazine Treatment in IBS, a Double-blind Placebo-controlled Phase II Intervention Study in Adult Patients</official_title>
  <sponsors>
    <lead_sponsor>
      <agency>Hans Törnblom</agency>
      <agency_class>Other</agency_class>
    </lead_sponsor>
    <collaborator>
      <agency>Sahlgrenska University Hospital, Sweden</agency>
      <agency_class>Other</agency_class>
    </collaborator>
    <collaborator>
      <agency>Smerud Medical Research International AS</agency>
      <agency_class>Other</agency_class>
    </collaborator>
    <collaborator>
      <agency>Alimenta AB</agency>
      <agency_class>Other</agency_class>
    </collaborator>
    <collaborator>
      <agency>Tillotts Pharma AG</agency>
      <agency_class>Industry</agency_class>
    </collaborator>
    <collaborator>
      <agency>Karolinska University Hospital</agency>
      <agency_class>Other</agency_class>
    </collaborator>
    <collaborator>
      <agency>Haukeland University Hospital</agency>
      <agency_class>Other</agency_class>
    </collaborator>
    <collaborator>
      <agency>Oslo University Hospital</agency>
      <agency_class>Other</agency_class>
    </collaborator>
    <collaborator>
      <agency>Sykehuset Innlandet HF</agency>
      <agency_class>Other</agency_class>
    </collaborator>
  </sponsors>
  <source>Göteborg University</source>
  <oversight_info>
    <has_dmc>Yes</has_dmc>
  </oversight_info>
  <brief_summary>
    <textblock>
      Irritable bowel syndrome (IBS) is a condition characterised by abdominal pain or discomfort&#xD;
      in combination with altered bowel function (stool frequency and/or stool consistency),&#xD;
      currently defined by the Rome III criteria. The current IBS definition specifies that there&#xD;
      are no structural or biochemical abnormalities to account for the symptoms but there is&#xD;
      growing evidence that in at least a subset of IBS patients, a discrete immune activation&#xD;
      might be a key pathogenetic factor. The condition is prone to develop after a&#xD;
      gastroenteritis, post-infectious IBS, and increased numbers of lymphocytes, mast cells and&#xD;
      pro-inflammatory cytokines like Interleukin (IL)-1β, IL-6, Tumor necrosis factor (TNF)-α and&#xD;
      a general increase in mucosal cellularity have been reported. Despite this, the efficacy of&#xD;
      anti-inflammatory agents has been poorly investigated.&#xD;
&#xD;
      This will be a randomised, double blind, placebo-controlled, parallel-group, multi-centre&#xD;
      study that aims to include a total of 200 subjects with irritable bowel syndrome (IBS). All&#xD;
      subjects will be randomised to receive either 3x800 mg of mesalazine (Asacol®) or&#xD;
      corresponding placebo once daily for a total treatment duration of 8 weeks. Males and females&#xD;
      aged 18 to 70 years who already are diagnosed with IBS based on the Rome III diagnostic&#xD;
      criteria and with a symptom intensity of at least moderate level; defined as an IBS Severity&#xD;
      Scoring System (IBS-SSS) score of ≥175 at both Screening (Visit 1, Day -21±2) and Baseline&#xD;
      (Visit 2, Day 0) will be eligible to enter the study.&#xD;
&#xD;
      Primary aim:&#xD;
&#xD;
      To assess the effect of mesalazine (Asacol®) treatment compared to placebo on global IBS&#xD;
      symptoms: A treatment responder will be defined by answering the satisfactory relief of&#xD;
      IBS-symptoms question &quot;yes&quot; at the end of at least 4 out of of 8 treatment weeks.&#xD;
&#xD;
      Secondary aims:&#xD;
&#xD;
      To assess mesalazine (Asacol®) treatment compared to placebo regarding:&#xD;
&#xD;
        1. Levels of inflammatory mediators in the rectal mucosa (e.g. neutrophil mediators,&#xD;
           eosinophilic mediators, mast cell activity mediators and cytokines) measured by a new&#xD;
           diagnostic tool, the Mucosal Patch Technology (MPT) by means of Enzyme-Linked&#xD;
           Immunosorbent Assays (ELISA)&#xD;
&#xD;
        2. Effects on number of immune cells (count per high power field) and cytokine content&#xD;
           (immunohistochemistry) in mucosal biopsies&#xD;
&#xD;
        3. Calprotectin levels in faeces (mg/kg)&#xD;
&#xD;
        4. Individual IBS symptom parameters derived from a symptom diary and also measured by&#xD;
           IBS-SSS&#xD;
    </textblock>
  </brief_summary>
  <overall_status>Completed</overall_status>
  <start_date type="Actual">April 2012</start_date>
  <completion_date type="Actual">February 2017</completion_date>
  <primary_completion_date type="Actual">December 2016</primary_completion_date>
  <phase>Phase 2</phase>
  <study_type>Interventional</study_type>
  <has_expanded_access>No</has_expanded_access>
  <study_design_info>
    <allocation>Randomized</allocation>
    <intervention_model>Parallel Assignment</intervention_model>
    <primary_purpose>Treatment</primary_purpose>
    <masking>Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)</masking>
  </study_design_info>
  <primary_outcome>
    <measure>Global Irritable Bowel Syndrome (IBS) symptoms</measure>
    <time_frame>8 weeks</time_frame>
    <description>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 &quot;yes&quot; ≥50% of the weeks (≥4 weeks)</description>
  </primary_outcome>
  <secondary_outcome>
    <measure>Inflammatory mediators</measure>
    <time_frame>8 weeks</time_frame>
    <description>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).</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Effect on immune cells and cytokines in mucosal biopsies</measure>
    <time_frame>8 weeks</time_frame>
    <description>Counts per high-power field in microscopy and by immunohistochemistry</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Levels of calprotectin in faeces</measure>
    <time_frame>8 weeks</time_frame>
    <description>Enzyme-Linked Immunosorbent Assay (ELISA), mg/kg</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Change in total IBS symptom severity score (IBS-SSS)</measure>
    <time_frame>8 weeks</time_frame>
    <description>Absolute change in IBS-SSS compared to baseline.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Individual symptom parameters in IBS symptom severity score (IBS-SSS) and the IBS diary</measure>
    <time_frame>8 weeks</time_frame>
    <description>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.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Exploratory responder variables</measure>
    <time_frame>8 weeks</time_frame>
    <description>Satisfactory symptom relief ≥75% of the time&#xD;
Reduction in IBS-SSS ≥50 at end of treatment compared to baseline</description>
  </secondary_outcome>
  <number_of_arms>2</number_of_arms>
  <enrollment type="Actual">211</enrollment>
  <condition>Irritable Bowel Syndrome</condition>
  <arm_group>
    <arm_group_label>Mesalazine</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
  </arm_group>
  <arm_group>
    <arm_group_label>Placebo</arm_group_label>
    <arm_group_type>Placebo Comparator</arm_group_type>
  </arm_group>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>Mesalazine</intervention_name>
    <description>2400 mg q.d. for 8 weeks</description>
    <arm_group_label>Mesalazine</arm_group_label>
    <other_name>Asacol</other_name>
  </intervention>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>Placebo</intervention_name>
    <description>3 tablets q.d. for 8 weeks</description>
    <arm_group_label>Placebo</arm_group_label>
  </intervention>
  <eligibility>
    <criteria>
      <textblock>
        Inclusion Criteria:&#xD;
&#xD;
          -  Males and females aged 18 to 70 years, both inclusive&#xD;
&#xD;
          -  Subject is diagnosed with irritable bowel syndrome (IBS) prior to Screening based on&#xD;
             the Rome III diagnostic criteria.&#xD;
&#xD;
          -  Subject presents with IBS symptom intensity of at least moderate level; defined as an&#xD;
             IBS Severity Scoring System (IBS-SSS) score of ≥175 at both Screening (Visit 1, Day&#xD;
             -21±2) and Baseline (Visit 2, Day 0)&#xD;
&#xD;
          -  Provision of signed informed consent&#xD;
&#xD;
        Exclusion Criteria:&#xD;
&#xD;
          -  Subjects who are unable to understand the written and verbal instructions&#xD;
&#xD;
          -  Presence of a systemic inflammatory disease&#xD;
&#xD;
          -  Presence of other gastrointestinal diseases likely to explain the IBS symptoms&#xD;
&#xD;
          -  Presence of other severe somatic disease&#xD;
&#xD;
          -  Treatment with non-steroidal anti-inflammatory drugs (NSAID), opioid analgetics or&#xD;
             acetylsalicylic acid (ASA) compounds within 7 days prior to screening (Visit 1, Day&#xD;
             -21±2)&#xD;
&#xD;
          -  Treatment with systemic antibiotics within 28 days prior to Screening (Visit 1, Day&#xD;
             -21±2)&#xD;
&#xD;
          -  Treatment with immunosuppressant drugs within 28 days prior to Screening (Visit 1, Day&#xD;
             -21±2)&#xD;
&#xD;
          -  Other significant medical treatment, which, in the opinion of the investigator, may&#xD;
             compromise the safety and efficacy objectives of the study, within 28 days prior to&#xD;
             Screening (Visit 1, Day -21±2)&#xD;
&#xD;
          -  Previously confirmed allergy towards ASA or mesalazine&#xD;
&#xD;
          -  Presence of renal disease and/or concomitant treatment with medications with potential&#xD;
             renal side effects&#xD;
&#xD;
          -  Current ongoing infection&#xD;
&#xD;
          -  History of, or current, drug or alcohol dependence&#xD;
&#xD;
          -  Pregnant or lactating women&#xD;
&#xD;
          -  Subjects suspected not to follow instructions based on the discretion of the&#xD;
             Investigator&#xD;
&#xD;
          -  Current participation in other intervention studies&#xD;
&#xD;
          -  Female subjects of childbearing potential unwilling to use adequate contraceptive&#xD;
             measures throughout the duration of the study.&#xD;
      </textblock>
    </criteria>
    <gender>All</gender>
    <minimum_age>18 Years</minimum_age>
    <maximum_age>70 Years</maximum_age>
    <healthy_volunteers>No</healthy_volunteers>
  </eligibility>
  <overall_official>
    <last_name>Hans Törnblom, MD, PhD</last_name>
    <role>Principal Investigator</role>
    <affiliation>Sahlgrenska University Hospital, Sweden</affiliation>
  </overall_official>
  <location>
    <facility>
      <name>Sahlgrenska University Hospital</name>
      <address>
        <city>Göteborg</city>
        <country>Sweden</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Karolinska University Hospital</name>
      <address>
        <city>Huddinge</city>
        <country>Sweden</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Norrland's University Hospital</name>
      <address>
        <city>Umeå</city>
        <country>Sweden</country>
      </address>
    </facility>
  </location>
  <location_countries>
    <country>Sweden</country>
  </location_countries>
  <verification_date>February 2017</verification_date>
  <study_first_submitted>September 16, 2012</study_first_submitted>
  <study_first_submitted_qc>September 30, 2012</study_first_submitted_qc>
  <study_first_posted type="Estimate">October 3, 2012</study_first_posted>
  <last_update_submitted>February 23, 2017</last_update_submitted>
  <last_update_submitted_qc>February 23, 2017</last_update_submitted_qc>
  <last_update_posted type="Actual">February 24, 2017</last_update_posted>
  <responsible_party>
    <responsible_party_type>Sponsor-Investigator</responsible_party_type>
    <investigator_affiliation>Göteborg University</investigator_affiliation>
    <investigator_full_name>Hans Törnblom</investigator_full_name>
    <investigator_title>MD, PhD</investigator_title>
  </responsible_party>
  <keyword>Irritable Bowel Syndrome</keyword>
  <keyword>Inflammation</keyword>
  <keyword>Mesalazine</keyword>
  <condition_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Irritable Bowel Syndrome</mesh_term>
  </condition_browse>
  <intervention_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Mesalamine</mesh_term>
  </intervention_browse>
  <!-- Results have not yet been posted for this study                                          -->
</clinical_study>


download date: ClinicalTrials.gov processed this data on September 20, 2023
link text: Link to the current ClinicalTrials.gov record.
url: https://clinicaltrials.gov/ct2/show/NCT01699438
org study id: SMR-2268
nct id: NCT01699438
lead sponsor: 
collaborator: 
collaborator: 
collaborator: 
collaborator: 
collaborator: 
collaborator: 
collaborator: 
collaborator: 
has dmc: Yes
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
allocation: Randomized
intervention model: Parallel Assignment
primary purpose: Treatment
masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
measure: Global Irritable Bowel Syndrome (IBS) symptoms
time frame: 8 weeks
description: 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)
measure: Inflammatory mediators
time frame: 8 weeks
description: 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).
measure: Effect on immune cells and cytokines in mucosal biopsies
time frame: 8 weeks
description: Counts per high-power field in microscopy and by immunohistochemistry
measure: Levels of calprotectin in faeces
time frame: 8 weeks
description: Enzyme-Linked Immunosorbent Assay (ELISA), mg/kg
measure: Change in total IBS symptom severity score (IBS-SSS)
time frame: 8 weeks
description: Absolute change in IBS-SSS compared to baseline.
measure: Individual symptom parameters in IBS symptom severity score (IBS-SSS) and the IBS diary
time frame: 8 weeks
description: 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.
measure: Exploratory responder variables
time frame: 8 weeks
description: Satisfactory symptom relief ≥75% of the time
Reduction in IBS-SSS ≥50 at end of treatment compared to baseline
arm group label: Mesalazine
arm group type: Experimental
arm group label: Placebo
arm group type: Placebo Comparator
intervention type: Drug
intervention name: Mesalazine
description: 2400 mg q.d. for 8 weeks
arm group label: Mesalazine
other name: Asacol
intervention type: Drug
intervention name: Placebo
description: 3 tablets q.d. for 8 weeks
arm group label: Placebo
criteria: 
gender: All
minimum age: 18 Years
maximum age: 70 Years
healthy volunteers: No
last name: Hans Törnblom, MD, PhD
role: Principal Investigator
affiliation: Sahlgrenska University Hospital, Sweden
facility: 
facility: 
facility: 
country: Sweden
responsible party type: Sponsor-Investigator
investigator affiliation: Göteborg University
investigator full name: Hans Törnblom
investigator title: MD, PhD
mesh term: Irritable Bowel Syndrome
mesh term: Mesalamine