<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/NCT03266484</url>
  </required_header>
  <id_info>
    <org_study_id>2017P001489</org_study_id>
    <nct_id>NCT03266484</nct_id>
  </id_info>
  <brief_title>Effect of a Probiotic Mixture on the Gut Microbiome and Fatigue in Patients With Quiescent Inflammatory Bowel Disease</brief_title>
  <official_title>Effect of Dietary Therapy With a Probiotic Mixture on the Gut Microbiome and Fatigue Symptoms in Patients With Quiescent Inflammatory Bowel Disease - A Clinical Trial</official_title>
  <sponsors>
    <lead_sponsor>
      <agency>Massachusetts General Hospital</agency>
      <agency_class>Other</agency_class>
    </lead_sponsor>
    <collaborator>
      <agency>Winclove Bio Industries BV</agency>
      <agency_class>Industry</agency_class>
    </collaborator>
  </sponsors>
  <source>Massachusetts General Hospital</source>
  <oversight_info>
    <has_dmc>No</has_dmc>
    <is_fda_regulated_drug>No</is_fda_regulated_drug>
    <is_fda_regulated_device>No</is_fda_regulated_device>
    <is_us_export>No</is_us_export>
  </oversight_info>
  <brief_summary>
    <textblock>
      The study is proposed as a single-site randomized double-blind placebo-controlled trial&#xD;
      requiring 4 study visits, where two of the visits are combined with their appointment for&#xD;
      routine clinical care. The study population will consist of patients with quiescent CD and UC&#xD;
      and IBD-unspecified recruited from the Massachusetts General Hospital Crohn's and Colitis&#xD;
      center. All eligible subjects will have a confirmed diagnosis of CD, UC, or IBD-unspecified&#xD;
      according to accepted clinical, endoscopic, radiologic, and histologic criteria. Eligible&#xD;
      patients will be contacted at the time of their routinely scheduled office visit and&#xD;
      consented for the study. Self-report and review of medical records will be used to obtain&#xD;
      detailed information regarding their disease on an intake questionnaire completed by a&#xD;
      research study coordinator.&#xD;
&#xD;
      The study is proposed as a 12-week double-blind randomized controlled trial of the probiotic&#xD;
      supplement compared to placebo. We propose to examine the effect of a specific probiotic&#xD;
      supplement on the changes in the gut microbiome, serum metabolomic profile, and fatigue&#xD;
      symptoms in patients with quiescent IBD.&#xD;
&#xD;
      Within 2 weeks of screening, eligible patients will be invited to visit MGH for a baseline&#xD;
      visit. The patient will receive either the probiotic supplement or placebo for 4 weeks.&#xD;
&#xD;
      The first follow up visit will be at week 4 to check for adverse events on study treatment,&#xD;
      to check accountability of probiotics/placebo, and to complete the set of questionnaires.&#xD;
      Also, subjects will receive probiotic/placebo samples for the remaining 8 weeks of treatment.&#xD;
&#xD;
      At week 8, subjects will receive a phone call from a study research coordinator to check in&#xD;
      with probiotics/placebo intake for treatment compliance and accountability records, and to&#xD;
      complete the set of questionnaires ascertaining subjective symptoms.&#xD;
&#xD;
      Last study visit will be at week 12 which is often combined with a regular office&#xD;
      appointment. Subject will provide serum blood and stool sample, as well as complete the set&#xD;
      of questionnaires.&#xD;
    </textblock>
  </brief_summary>
  <overall_status>Active, not recruiting</overall_status>
  <start_date type="Actual">November 13, 2017</start_date>
  <completion_date type="Anticipated">July 2024</completion_date>
  <primary_completion_date type="Anticipated">July 2024</primary_completion_date>
  <phase>N/A</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>Diagnostic</primary_purpose>
    <masking>Triple (Participant, Care Provider, Investigator)</masking>
    <masking_description>Will be a double blinded randomized controlled trial. Masking will be done by the provider of the probiotics/placebo</masking_description>
  </study_design_info>
  <primary_outcome>
    <measure>Change in gut microbiome</measure>
    <time_frame>Week 12</time_frame>
    <description>Change in fecal microbiome pattern assessed using 16sRNA sequencing.</description>
  </primary_outcome>
  <primary_outcome>
    <measure>Change in serum inflammatory cytokines levels</measure>
    <time_frame>Week 12</time_frame>
    <description>Change in inflammatory cytokines will be performed using the Biosciences Cytometric Bead Array kits.</description>
  </primary_outcome>
  <primary_outcome>
    <measure>Change in metabolomic profiles</measure>
    <time_frame>Week 12</time_frame>
    <description>Change in metabolic profiling will be performed on serum samples using established targeted quantitative and semi-quantitative gas chromatography-mass spectrometry (GC-MS) and liquid chromatography-mass spectrometry (LC-MS) methods</description>
  </primary_outcome>
  <primary_outcome>
    <measure>Change in fatigue symptoms</measure>
    <time_frame>Week 4 and Week 12</time_frame>
    <description>Reduction of fatigue symptoms which will be assessed using FACIT-F questionnaire. FACIT-F score of &gt;43 at week 4 or week 12</description>
  </primary_outcome>
  <number_of_arms>2</number_of_arms>
  <enrollment type="Anticipated">100</enrollment>
  <condition>Inflammatory Bowel Diseases</condition>
  <condition>Crohn Disease</condition>
  <condition>Ulcerative Colitis</condition>
  <arm_group>
    <arm_group_label>Probiotic Mixture</arm_group_label>
    <arm_group_type>Active Comparator</arm_group_type>
    <description>Participants who are meeting the inclusion criteria will be randomized to either the probiotic mixture or an identical placebo.&#xD;
The probiotics sachets will be taken twice a day for 12 weeks.</description>
  </arm_group>
  <arm_group>
    <arm_group_label>Placebo</arm_group_label>
    <arm_group_type>Placebo Comparator</arm_group_type>
    <description>Participants who are meeting the inclusion criteria will be randomized to either the probiotic mixture or an identical placebo&#xD;
The identical placebo sachets will be taken twice a day for 12 weeks.</description>
  </arm_group>
  <intervention>
    <intervention_type>Dietary Supplement</intervention_type>
    <intervention_name>Probiotic Mixture</intervention_name>
    <description>The probiotic supplement contains 8 different strains of bacteria and participants will be dosed in two dosages per a total of 40 billion bacteria daily.</description>
    <arm_group_label>Probiotic Mixture</arm_group_label>
  </intervention>
  <intervention>
    <intervention_type>Dietary Supplement</intervention_type>
    <intervention_name>Placebo</intervention_name>
    <description>A placebo which is identical to the probiotic mixture. Participants will be dosed in two dosages daily.</description>
    <arm_group_label>Placebo</arm_group_label>
  </intervention>
  <eligibility>
    <criteria>
      <textblock>
        Inclusion Criteria:&#xD;
&#xD;
          -  Age 18-75 years&#xD;
&#xD;
          -  Confirmed CD or UC or IBD-unspecified diagnosed according to standard criteria&#xD;
&#xD;
          -  Quiescent disease defined as Harvey Bradshaw index &lt; 4 at baseline (week 0) or SCCAI &lt;&#xD;
             2&#xD;
&#xD;
          -  Persistent ongoing fatigue symptoms&#xD;
&#xD;
          -  Endoscopic or radiologic remission within 12 months of screening&#xD;
&#xD;
          -  Washout of non-study probiotic supplements for at least 4 weeks prior to screening.&#xD;
&#xD;
        Exclusion Criteria:&#xD;
&#xD;
          -  Patients with clinical or endoscopically active inflammatory bowel disease&#xD;
&#xD;
          -  Significant non-IBD comorbidity contributing to the fatigue (such as active cancer).&#xD;
&#xD;
          -  Untreated severe depression or anxiety&#xD;
&#xD;
          -  Known sleep disorders without adequate treatment,&#xD;
&#xD;
          -  Presence of J-pouch or a stoma&#xD;
&#xD;
          -  Ongoing use of other non-study probiotics&#xD;
&#xD;
          -  Women who are pregnant or lactating&#xD;
      </textblock>
    </criteria>
    <gender>All</gender>
    <minimum_age>18 Years</minimum_age>
    <maximum_age>75 Years</maximum_age>
    <healthy_volunteers>No</healthy_volunteers>
  </eligibility>
  <overall_official>
    <last_name>Ashwin N Ananthakrishnan, MBBS, MPH</last_name>
    <role>Principal Investigator</role>
    <affiliation>Massachusetts General Hospital</affiliation>
  </overall_official>
  <location>
    <facility>
      <name>Crohn's and Colitis Center, MGH</name>
      <address>
        <city>Boston</city>
        <state>Massachusetts</state>
        <zip>02114</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location_countries>
    <country>United States</country>
  </location_countries>
  <verification_date>March 2023</verification_date>
  <study_first_submitted>August 25, 2017</study_first_submitted>
  <study_first_submitted_qc>August 28, 2017</study_first_submitted_qc>
  <study_first_posted type="Actual">August 30, 2017</study_first_posted>
  <last_update_submitted>March 13, 2023</last_update_submitted>
  <last_update_submitted_qc>March 13, 2023</last_update_submitted_qc>
  <last_update_posted type="Actual">March 14, 2023</last_update_posted>
  <responsible_party>
    <responsible_party_type>Principal Investigator</responsible_party_type>
    <investigator_affiliation>Massachusetts General Hospital</investigator_affiliation>
    <investigator_full_name>Ashwin Ananthakrishnan</investigator_full_name>
    <investigator_title>Assistant Professor of Medicine</investigator_title>
  </responsible_party>
  <keyword>Microbiome</keyword>
  <keyword>Fatigue</keyword>
  <keyword>Probiotics</keyword>
  <condition_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Crohn Disease</mesh_term>
    <mesh_term>Intestinal Diseases</mesh_term>
    <mesh_term>Inflammatory Bowel Diseases</mesh_term>
    <mesh_term>Fatigue</mesh_term>
  </condition_browse>
  <patient_data>
    <sharing_ipd>No</sharing_ipd>
  </patient_data>
  <!-- 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/NCT03266484
org study id: 2017P001489
nct id: NCT03266484
lead sponsor: 
collaborator: 
has dmc: No
is fda regulated drug: No
is fda regulated device: No
is us export: No
The study is proposed as a single-site randomized double-blind placebo-controlled trial
      requiring 4 study visits, where two of the visits are combined with their appointment for
      routine clinical care. The study population will consist of patients with quiescent CD and UC
      and IBD-unspecified recruited from the Massachusetts General Hospital Crohn's and Colitis
      center. All eligible subjects will have a confirmed diagnosis of CD, UC, or IBD-unspecified
      according to accepted clinical, endoscopic, radiologic, and histologic criteria. Eligible
      patients will be contacted at the time of their routinely scheduled office visit and
      consented for the study. Self-report and review of medical records will be used to obtain
      detailed information regarding their disease on an intake questionnaire completed by a
      research study coordinator.

      The study is proposed as a 12-week double-blind randomized controlled trial of the probiotic
      supplement compared to placebo. We propose to examine the effect of a specific probiotic
      supplement on the changes in the gut microbiome, serum metabolomic profile, and fatigue
      symptoms in patients with quiescent IBD.

      Within 2 weeks of screening, eligible patients will be invited to visit MGH for a baseline
      visit. The patient will receive either the probiotic supplement or placebo for 4 weeks.

      The first follow up visit will be at week 4 to check for adverse events on study treatment,
      to check accountability of probiotics/placebo, and to complete the set of questionnaires.
      Also, subjects will receive probiotic/placebo samples for the remaining 8 weeks of treatment.

      At week 8, subjects will receive a phone call from a study research coordinator to check in
      with probiotics/placebo intake for treatment compliance and accountability records, and to
      complete the set of questionnaires ascertaining subjective symptoms.

      Last study visit will be at week 12 which is often combined with a regular office
      appointment. Subject will provide serum blood and stool sample, as well as complete the set
      of questionnaires.
allocation: Randomized
intervention model: Parallel Assignment
primary purpose: Diagnostic
masking: Triple (Participant, Care Provider, Investigator)
masking description: Will be a double blinded randomized controlled trial. Masking will be done by the provider of the probiotics/placebo
measure: Change in gut microbiome
time frame: Week 12
description: Change in fecal microbiome pattern assessed using 16sRNA sequencing.
measure: Change in serum inflammatory cytokines levels
time frame: Week 12
description: Change in inflammatory cytokines will be performed using the Biosciences Cytometric Bead Array kits.
measure: Change in metabolomic profiles
time frame: Week 12
description: Change in metabolic profiling will be performed on serum samples using established targeted quantitative and semi-quantitative gas chromatography-mass spectrometry (GC-MS) and liquid chromatography-mass spectrometry (LC-MS) methods
measure: Change in fatigue symptoms
time frame: Week 4 and Week 12
description: Reduction of fatigue symptoms which will be assessed using FACIT-F questionnaire. FACIT-F score of >43 at week 4 or week 12
arm group label: Probiotic Mixture
arm group type: Active Comparator
description: Participants who are meeting the inclusion criteria will be randomized to either the probiotic mixture or an identical placebo.
The probiotics sachets will be taken twice a day for 12 weeks.
arm group label: Placebo
arm group type: Placebo Comparator
description: Participants who are meeting the inclusion criteria will be randomized to either the probiotic mixture or an identical placebo
The identical placebo sachets will be taken twice a day for 12 weeks.
intervention type: Dietary Supplement
intervention name: Probiotic Mixture
description: The probiotic supplement contains 8 different strains of bacteria and participants will be dosed in two dosages per a total of 40 billion bacteria daily.
arm group label: Probiotic Mixture
intervention type: Dietary Supplement
intervention name: Placebo
description: A placebo which is identical to the probiotic mixture. Participants will be dosed in two dosages daily.
arm group label: Placebo
criteria: 
gender: All
minimum age: 18 Years
maximum age: 75 Years
healthy volunteers: No
last name: Ashwin N Ananthakrishnan, MBBS, MPH
role: Principal Investigator
affiliation: Massachusetts General Hospital
facility: 
country: United States
responsible party type: Principal Investigator
investigator affiliation: Massachusetts General Hospital
investigator full name: Ashwin Ananthakrishnan
investigator title: Assistant Professor of Medicine
mesh term: Crohn Disease
mesh term: Intestinal Diseases
mesh term: Inflammatory Bowel Diseases
mesh term: Fatigue
sharing ipd: No