<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/NCT02251483</url>
  </required_header>
  <id_info>
    <org_study_id>35543</org_study_id>
    <nct_id>NCT02251483</nct_id>
  </id_info>
  <brief_title>Use of SBI in IBS Subjects Following a Successful Treatment of Small Intestinal Bacterial Overgrowth</brief_title>
  <official_title>Use of Serum-derived Immunoglobulin/Protein Isolate (SBI) for the Maintenance of Health in Subjects With Irritable Bowel Syndrome (IBS) Following Successful Treatment of Small Intestinal Bacterial Overgrowth (SIBO)</official_title>
  <sponsors>
    <lead_sponsor>
      <agency>Cedars-Sinai Medical Center</agency>
      <agency_class>Other</agency_class>
    </lead_sponsor>
    <collaborator>
      <agency>Entera Health, Inc</agency>
      <agency_class>Industry</agency_class>
    </collaborator>
  </sponsors>
  <source>Cedars-Sinai Medical Center</source>
  <oversight_info>
    <has_dmc>Yes</has_dmc>
  </oversight_info>
  <brief_summary>
    <textblock>
      The primary objective of this study is to determine whether giving SBI as a medical food&#xD;
      starting with maintenance of health in the management of chronic loose and frequent stools in&#xD;
      IBS-D subjects with SIBO after successful treatment with rifaximin can lead to more prolonged&#xD;
      duration of benefit and delay symptom recurrence. SBI is the main ingredient in EnteraGam™,&#xD;
      an orally administered prescription medical food for the dietary management of patients with&#xD;
      enteropathy or chronic loose or frequent stools, including patients with IBS-D.&#xD;
    </textblock>
  </brief_summary>
  <detailed_description>
    <textblock>
      Irritable bowel syndrome (IBS) is one of the most common gastrointestinal disorders, with a&#xD;
      global prevalence of 11%. IBS manifests itself in 3 major forms; diarrhea-predominant&#xD;
      (IBS-D), constipation-predominant (IBS-C), and mixed (IBS-M), and is predominantly&#xD;
      characterized by symptoms of abdominal pain, changes in stool frequency and consistency, and&#xD;
      abdominal bloating.&#xD;
&#xD;
      SIBO is a condition in which there is an increase in the number of bacteria in the small&#xD;
      bowel, and typically includes an overgrowth of coliform bacteria which are normally found in&#xD;
      the colon. These ferment carbohydrates into gas (which can be measured using the lactulose&#xD;
      breath test (LBT)), and the SIBO hypothesis proposes that it is this expansion of bacteria in&#xD;
      the small bowel that leads to IBS symptoms including bloating, abdominal discomfort and&#xD;
      changes in stool form. The antibiotic rifaximin is used to treat IBS-D, and has been shown to&#xD;
      normalize the LBT in 70% of subjects. Despite this success, symptoms such as SIBO tend to&#xD;
      recur, usually within 4 months of finishing the antibiotic treatment. Therefore, there&#xD;
      remains a significant need to identify therapeutic agents which can maintain the health of&#xD;
      subjects with IBS and SIBO and increase the duration of benefit in subjects with IBS and SIBO&#xD;
      following antibiotic treatment.&#xD;
&#xD;
      SBI is intended for the dietary management of enteropathy under medical supervision in&#xD;
      patients with chronic loose or frequent stools, including IBS-D patients. In vitro and animal&#xD;
      studies have shown that SBI supports digestive and absorptive properties of the intestinal&#xD;
      tracts by:&#xD;
&#xD;
        1. Binding and neutralizing microbial components&#xD;
&#xD;
        2. Helping to maintain beneficial gut microbiota&#xD;
&#xD;
        3. Managing gut barrier function&#xD;
&#xD;
        4. Maintaining GI immune balance&#xD;
&#xD;
      Clinical studies have also demonstrated that oral SBI improves nutrient absorption,&#xD;
      nutritional status and GI symptoms in patients with HIV-associated enteropathy, IBS-D, or&#xD;
      malnutrition. It is important to note that SBI is not used to treat patients with IBS-D or&#xD;
      other enteropathies, but is given as a medical food to assist in the maintenance of health&#xD;
      only.&#xD;
&#xD;
      This study will assess whether giving SBI as a medical food to subjects with IBS-D and SIBO&#xD;
      after they successfully complete a course of rifaximin can lead to more prolonged maintenance&#xD;
      of health and duration of benefit of antibiotic treatment in IBS-D patients.&#xD;
    </textblock>
  </detailed_description>
  <overall_status>Completed</overall_status>
  <start_date>September 2014</start_date>
  <completion_date type="Actual">July 2015</completion_date>
  <primary_completion_date type="Actual">July 2015</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>Supportive Care</primary_purpose>
    <masking>Double (Participant, Investigator)</masking>
  </study_design_info>
  <primary_outcome>
    <measure>Time to relapse (symptom recurrence) in subjects with IBS-D after successful treatment with rifaximin</measure>
    <time_frame>up to 4 months</time_frame>
  </primary_outcome>
  <secondary_outcome>
    <measure>Change in symptoms based on comparison of baseline symptom questionnaire to weekly symptom questionnaires</measure>
    <time_frame>baseline and weekly questionnaires for up to 4 months</time_frame>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Comparison of baseline Bristol stool score based on 7 day stool diary</measure>
    <time_frame>last week of every month for up to 4 months</time_frame>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Comparison of KT ratios in plasma samples</measure>
    <time_frame>up to 4 months</time_frame>
  </secondary_outcome>
  <number_of_arms>2</number_of_arms>
  <enrollment type="Actual">2</enrollment>
  <condition>Diarrhea Predominant Irritable Bowel Syndrome</condition>
  <condition>Small Intestinal Bacterial Overgrowth</condition>
  <arm_group>
    <arm_group_label>SBI</arm_group_label>
    <arm_group_type>Other</arm_group_type>
    <description>Group 1: SBI (N=30) - one packet daily</description>
  </arm_group>
  <arm_group>
    <arm_group_label>Placebo</arm_group_label>
    <arm_group_type>Placebo Comparator</arm_group_type>
    <description>Group 2: Placebo (N=30) - one packet daily</description>
  </arm_group>
  <intervention>
    <intervention_type>Other</intervention_type>
    <intervention_name>Serum-derived bovine immunoglobulin protein isolate (SBI)</intervention_name>
    <arm_group_label>SBI</arm_group_label>
  </intervention>
  <intervention>
    <intervention_type>Other</intervention_type>
    <intervention_name>Placebo</intervention_name>
    <arm_group_label>Placebo</arm_group_label>
  </intervention>
  <eligibility>
    <criteria>
      <textblock>
        Inclusion Criteria:&#xD;
&#xD;
          -  Male or female aged 18-75 years old&#xD;
&#xD;
          -  Meet Rome II criteria for IBS-D&#xD;
&#xD;
          -  Meet criteria for SIBO&#xD;
&#xD;
          -  If ≥50 years old, a colonoscopy must have been completed within the past 10 years&#xD;
&#xD;
          -  Have just completed a course of antibiotic treatment with rifaximin and successfully&#xD;
             responded to this treatment.&#xD;
&#xD;
        Exclusion Criteria:&#xD;
&#xD;
          -  Had intestinal surgery (except appendectomy or cholecystectomy)&#xD;
&#xD;
          -  Pelvic floor dysfunction&#xD;
&#xD;
          -  Pregnancy or nursing mothers&#xD;
&#xD;
          -  History of bowel obstruction&#xD;
&#xD;
          -  History of celiac disease&#xD;
&#xD;
          -  History of inflammatory bowel disease&#xD;
&#xD;
          -  Cirrhosis&#xD;
&#xD;
          -  Diabetes&#xD;
&#xD;
          -  Use of tricyclic antidepressants&#xD;
&#xD;
          -  Use of antidiarrheal medications&#xD;
&#xD;
          -  Allergy or hypersensitivity to beef or any component of SBI&#xD;
      </textblock>
    </criteria>
    <gender>All</gender>
    <minimum_age>18 Years</minimum_age>
    <maximum_age>75 Years</maximum_age>
    <healthy_volunteers>No</healthy_volunteers>
  </eligibility>
  <location>
    <facility>
      <name>GI Motility Program Cedars-Sinai Medical Center</name>
      <address>
        <city>Los Angeles</city>
        <state>California</state>
        <zip>90048</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location_countries>
    <country>United States</country>
  </location_countries>
  <verification_date>July 2015</verification_date>
  <study_first_submitted>September 17, 2014</study_first_submitted>
  <study_first_submitted_qc>September 25, 2014</study_first_submitted_qc>
  <study_first_posted type="Estimate">September 29, 2014</study_first_posted>
  <last_update_submitted>July 27, 2015</last_update_submitted>
  <last_update_submitted_qc>July 27, 2015</last_update_submitted_qc>
  <last_update_posted type="Estimate">July 29, 2015</last_update_posted>
  <responsible_party>
    <responsible_party_type>Principal Investigator</responsible_party_type>
    <investigator_affiliation>Cedars-Sinai Medical Center</investigator_affiliation>
    <investigator_full_name>Mark Pimentel, MD</investigator_full_name>
    <investigator_title>Director, GI Motility Program</investigator_title>
  </responsible_party>
  <keyword>DIBS</keyword>
  <keyword>SIBO</keyword>
  <condition_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Irritable Bowel Syndrome</mesh_term>
    <mesh_term>Syndrome</mesh_term>
    <mesh_term>Diarrhea</mesh_term>
  </condition_browse>
  <intervention_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Immunoglobulins</mesh_term>
    <mesh_term>Immunoglobulins, Intravenous</mesh_term>
    <mesh_term>Antibodies</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/NCT02251483
org study id: 35543
nct id: NCT02251483
lead sponsor: 
collaborator: 
has dmc: Yes
The primary objective of this study is to determine whether giving SBI as a medical food
      starting with maintenance of health in the management of chronic loose and frequent stools in
      IBS-D subjects with SIBO after successful treatment with rifaximin can lead to more prolonged
      duration of benefit and delay symptom recurrence. SBI is the main ingredient in EnteraGam™,
      an orally administered prescription medical food for the dietary management of patients with
      enteropathy or chronic loose or frequent stools, including patients with IBS-D.
Irritable bowel syndrome (IBS) is one of the most common gastrointestinal disorders, with a
      global prevalence of 11%. IBS manifests itself in 3 major forms; diarrhea-predominant
      (IBS-D), constipation-predominant (IBS-C), and mixed (IBS-M), and is predominantly
      characterized by symptoms of abdominal pain, changes in stool frequency and consistency, and
      abdominal bloating.

      SIBO is a condition in which there is an increase in the number of bacteria in the small
      bowel, and typically includes an overgrowth of coliform bacteria which are normally found in
      the colon. These ferment carbohydrates into gas (which can be measured using the lactulose
      breath test (LBT)), and the SIBO hypothesis proposes that it is this expansion of bacteria in
      the small bowel that leads to IBS symptoms including bloating, abdominal discomfort and
      changes in stool form. The antibiotic rifaximin is used to treat IBS-D, and has been shown to
      normalize the LBT in 70% of subjects. Despite this success, symptoms such as SIBO tend to
      recur, usually within 4 months of finishing the antibiotic treatment. Therefore, there
      remains a significant need to identify therapeutic agents which can maintain the health of
      subjects with IBS and SIBO and increase the duration of benefit in subjects with IBS and SIBO
      following antibiotic treatment.

      SBI is intended for the dietary management of enteropathy under medical supervision in
      patients with chronic loose or frequent stools, including IBS-D patients. In vitro and animal
      studies have shown that SBI supports digestive and absorptive properties of the intestinal
      tracts by:

        1. Binding and neutralizing microbial components

        2. Helping to maintain beneficial gut microbiota

        3. Managing gut barrier function

        4. Maintaining GI immune balance

      Clinical studies have also demonstrated that oral SBI improves nutrient absorption,
      nutritional status and GI symptoms in patients with HIV-associated enteropathy, IBS-D, or
      malnutrition. It is important to note that SBI is not used to treat patients with IBS-D or
      other enteropathies, but is given as a medical food to assist in the maintenance of health
      only.

      This study will assess whether giving SBI as a medical food to subjects with IBS-D and SIBO
      after they successfully complete a course of rifaximin can lead to more prolonged maintenance
      of health and duration of benefit of antibiotic treatment in IBS-D patients.
allocation: Randomized
intervention model: Parallel Assignment
primary purpose: Supportive Care
masking: Double (Participant, Investigator)
measure: Time to relapse (symptom recurrence) in subjects with IBS-D after successful treatment with rifaximin
time frame: up to 4 months
measure: Change in symptoms based on comparison of baseline symptom questionnaire to weekly symptom questionnaires
time frame: baseline and weekly questionnaires for up to 4 months
measure: Comparison of baseline Bristol stool score based on 7 day stool diary
time frame: last week of every month for up to 4 months
measure: Comparison of KT ratios in plasma samples
time frame: up to 4 months
arm group label: SBI
arm group type: Other
description: Group 1: SBI (N=30) - one packet daily
arm group label: Placebo
arm group type: Placebo Comparator
description: Group 2: Placebo (N=30) - one packet daily
intervention type: Other
intervention name: Serum-derived bovine immunoglobulin protein isolate (SBI)
arm group label: SBI
intervention type: Other
intervention name: Placebo
arm group label: Placebo
criteria: 
gender: All
minimum age: 18 Years
maximum age: 75 Years
healthy volunteers: No
facility: 
country: United States
responsible party type: Principal Investigator
investigator affiliation: Cedars-Sinai Medical Center
investigator full name: Mark Pimentel, MD
investigator title: Director, GI Motility Program
mesh term: Irritable Bowel Syndrome
mesh term: Syndrome
mesh term: Diarrhea
mesh term: Immunoglobulins
mesh term: Immunoglobulins, Intravenous
mesh term: Antibodies