<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/NCT03795233</url>
  </required_header>
  <id_info>
    <org_study_id>H-37574</org_study_id>
    <nct_id>NCT03795233</nct_id>
  </id_info>
  <brief_title>Fecal Microbiota Transplant for Primary CDI</brief_title>
  <official_title>Fecal Microbiota Transplant (FMT) After Treatment for a First Episode of Clostridium Difficile Infection (CDI)</official_title>
  <sponsors>
    <lead_sponsor>
      <agency>Boston Medical Center</agency>
      <agency_class>Other</agency_class>
    </lead_sponsor>
  </sponsors>
  <source>Boston Medical Center</source>
  <oversight_info>
    <has_dmc>Yes</has_dmc>
    <is_fda_regulated_drug>Yes</is_fda_regulated_drug>
    <is_fda_regulated_device>No</is_fda_regulated_device>
  </oversight_info>
  <brief_summary>
    <textblock>
      Clostridium difficile infection (CDI) is one of the most urgent health threats in the U.S.&#xD;
      associated with antibiotic use. After an initial episode, disease recurrence is high and&#xD;
      relapses can occur in 20-30% of people treated with oral vancomycin. An antibiotic course can&#xD;
      affect the gut microbiome for years, and patients with CDI have additional dysbiosis of their&#xD;
      gut flora. Oral vancomycin perturbs the gut microbiome further. Restoration of the microbiome&#xD;
      with Fecal Microbiota Transplant (FMT) has been proven a highly efficacious and&#xD;
      cost-effective treatment for recurrent CDI. FMT has had very limited study for a primary&#xD;
      episode of CDI to date because an endoscopic procedure was the recommended route of delivery.&#xD;
      However, FMT is now available via frozen oral capsules and has been shown to be non-inferior&#xD;
      to FMT via colonoscopy in randomized controlled trials.&#xD;
&#xD;
      The investigators hypothesize that outcomes after a first episode of CDI can be improved if&#xD;
      the microbiome is restored with oral FMT. It is further hypothesized that this will&#xD;
      compensate for any additional microbiome perturbation caused by administration of oral&#xD;
      vancomycin and decrease the likelihood of recurrence. Because the hypothesis is based on&#xD;
      restoration of the microbiome, the investigators propose this proof-of-concept pilot study to&#xD;
      examine whether FMT administered after oral vancomycin therapy for primary CDI restores&#xD;
      microbiome diversity compared to patients who do not receive FMT. Because of the potential&#xD;
      health benefits, this approach deserves further study. The results from this pilot study on&#xD;
      the microbiome diversity as well as the surveys to be conducted about GI symptomatology&#xD;
      (e.g., diarrhea, abdominal pain, bloating), CDI recurrence and healthcare utilization, would&#xD;
      provide preliminary data to support a randomized controlled, multicenter clinical trial.&#xD;
    </textblock>
  </brief_summary>
  <detailed_description>
    <textblock>
      Population: Patients &gt;= 18 years hospitalized at Boston Medical Center (BMC) with a first&#xD;
      documented episode of CDI.&#xD;
&#xD;
      Intervention: 30 FMT capsules administered orally under direct observation within 7 days of&#xD;
      completion of 10-14 day treatment of oral vancomycin for CDI.&#xD;
&#xD;
      Objectives:&#xD;
&#xD;
        1. To characterize the microbial diversity in stool samples from subjects with a primary&#xD;
           episode of CDI before and after oral vancomycin and determine the impact of FMT after&#xD;
           completion of oral vancomycin course.&#xD;
&#xD;
        2. To characterize the feasibility and tolerability of FMT after completion of a course of&#xD;
           oral vancomycin therapy for primary CDI, and to describe 30-day hospital readmission and&#xD;
           gastrointestinal symptomatology and/or CDI recurrence during 60-day follow-up.&#xD;
&#xD;
      Design/Methodology:&#xD;
&#xD;
      15 subjects will be enrolled who are hospitalized at BMC for a primary episode of CDI. A&#xD;
      discard aliquot from baseline stool samples obtained clinically for diagnosis will be frozen.&#xD;
      Subjects will receive the standard of care treatment (oral vancomycin for 10-14 days) and&#xD;
      within 7 days following completion will receive oral FMT during a 2 hour visit in the&#xD;
      Infectious Disease (ID) Clinical Trials Unit. An additional 5 subjects will be enrolled as&#xD;
      controls. Stool samples will be collected at time of CDI diagnosis and again 3 weeks after&#xD;
      FMT for intervention group and 4 weeks after completion of oral vancomycin treatment for&#xD;
      control subjects. The post-treatment samples will be obtained by the patient using special&#xD;
      stool sample collection kits known as RNAlater kits (ribonucleic acid stabilization). These&#xD;
      contain a liquid nontoxic tissue storage reagent known as RNAlater and helps preserve the&#xD;
      stool sample. The subjects will mail this stool sample to the BMC Clinical Trials Unit (CTU)&#xD;
      where it will aliquoted, centrifuged and frozen.&#xD;
&#xD;
      Samples will be processed at a collaborating lab at Tufts to characterize the fecal&#xD;
      microbiome pre- and post oral FMT.&#xD;
&#xD;
      Study personnel will contact participants via telephone 60 days after FMT dosing to&#xD;
      administer a follow-up survey (including questions on residual symptoms. CDI recurrence,&#xD;
      re-hospitalization, adverse events and FMT acceptability).&#xD;
&#xD;
      Total Study Duration: Anticipated time: 12 months&#xD;
&#xD;
      Subject Participation Duration: The researchers anticipate a period of 1-2 hours while an&#xD;
      inpatient for the screening and consent process, 2 hours for the CTU visit for FMT and 20-30&#xD;
      minutes responding to a follow up telephone survey. Total time in the study from enrollment&#xD;
      to completion of follow-up will be approximately 3 months and will include 10-14 days of CDI&#xD;
      treatment with oral vancomycin (per standard of care treatment), the FMT administration and a&#xD;
      60 day follow up.&#xD;
    </textblock>
  </detailed_description>
  <overall_status>Terminated</overall_status>
  <why_stopped>
    The study was terminated after a covid-related suspension and the unavailability of drug.&#xD;
  </why_stopped>
  <start_date type="Actual">August 23, 2019</start_date>
  <completion_date type="Actual">January 15, 2021</completion_date>
  <primary_completion_date type="Actual">January 15, 2021</primary_completion_date>
  <phase>Phase 1/Phase 2</phase>
  <study_type>Interventional</study_type>
  <has_expanded_access>No</has_expanded_access>
  <study_design_info>
    <allocation>Non-Randomized</allocation>
    <intervention_model>Parallel Assignment</intervention_model>
    <primary_purpose>Treatment</primary_purpose>
    <masking>None (Open Label)</masking>
  </study_design_info>
  <primary_outcome>
    <measure>Stool Microbiome With and Without FMT Administration</measure>
    <time_frame>11 months</time_frame>
    <description>The stool microbiome in participants who receive additional FMT at end of Clostridium difficile infection (CDI) treatment with oral vancomycin will be compared to the stool microbiome in participants with standard treatment or oral vancomycin alone</description>
  </primary_outcome>
  <secondary_outcome>
    <measure>Feasibility of Administering FMT After Completion of a Course of Oral Vancomycin Therapy</measure>
    <time_frame>12 months</time_frame>
    <description>The number and proportion of FMT pills participants ingest after completion of a course of oral vancomycin therapy will be documented.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Incidence of Treatment-Emergent Adverse Events [Safety and Tolerability] of FMT After a Course of Oral Vancomycin Therapy</measure>
    <time_frame>During test dose, during 90 minutes of FMT administration, 30 minutes after FMT administration, 48-72 hours after FMT administration</time_frame>
    <description>Study participants will be monitored for any adverse events to FMT such as nausea or vomiting, abdominal pain or diarrhea.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Incidence of Gastrointestinal Symptomatology Based on a Survey After CDI</measure>
    <time_frame>60 days</time_frame>
    <description>A detailed survey with 15 questions will be administered on GI symptoms Physicians will go over any significant adverse events to determine if they are related, possibly related or unrelated to oral FMT administration</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>CDI Recurrence</measure>
    <time_frame>60 days</time_frame>
    <description>Patients will be monitored for recurrent C difficile infection defined as non-resolution or recurrence of GI symptoms (abdominal pain, diarrhea etc) and/or a positive stool C difficile test The proportion of participants with CDI recurrence will be documented.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Number of Hospital Readmissions After Treatment</measure>
    <time_frame>30 days</time_frame>
    <description>The number of hospital readmissions within 30 days after CDI treatment per patient history and chart review will be obtained</description>
  </secondary_outcome>
  <number_of_arms>2</number_of_arms>
  <enrollment type="Actual">5</enrollment>
  <condition>Clostridium Difficile Infection</condition>
  <arm_group>
    <arm_group_label>Fecal microbiota transplantation</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>Fecal microbiota transplant G3 capsules will be administered after standard of care with oral vancomycin therapy in participants with primary Clostridium difficile infection.</description>
  </arm_group>
  <arm_group>
    <arm_group_label>Oral vancomycin alone (Control)</arm_group_label>
    <arm_group_type>Active Comparator</arm_group_type>
    <description>Oral vancomycin therapy will be administered as per standard of care in participants with primary clostridium difficile infection.</description>
  </arm_group>
  <intervention>
    <intervention_type>Biological</intervention_type>
    <intervention_name>Fecal microbiota transplant G3 capsules</intervention_name>
    <description>After standard of care therapy with oral vancomycin, frozen oral FMT capsules will be provided in a formulation designed to deliver the product to the large intestine. 30 FMT capsules will be administered over a 2 hour period under direct observation</description>
    <arm_group_label>Fecal microbiota transplantation</arm_group_label>
    <other_name>FMT</other_name>
  </intervention>
  <intervention>
    <intervention_type>Other</intervention_type>
    <intervention_name>Oral Vancomycin alone</intervention_name>
    <description>Standard of care will be provided with oral vancomycin therapy.</description>
    <arm_group_label>Oral vancomycin alone (Control)</arm_group_label>
    <other_name>Oral Vancocin alone</other_name>
  </intervention>
  <eligibility>
    <criteria>
      <textblock>
        Inclusion Criteria:&#xD;
&#xD;
          -  Diagnosis of primary clostridium difficile infection (CDI) defined by the presence of&#xD;
             diarrhea and a positive C. difficile Polymerase chain reaction (PCR) test&#xD;
&#xD;
          -  Admitted to Boston Medical Center&#xD;
&#xD;
          -  English speaking&#xD;
&#xD;
        Exclusion Criteria:&#xD;
&#xD;
          -  Primary CDI treatment failure&#xD;
&#xD;
          -  History of CDI&#xD;
&#xD;
          -  Diagnosis of inflammatory bowel disease, immunocompromised state, or active malignancy&#xD;
&#xD;
          -  Dysphagia: oropharyngeal, esophageal, functional, neuromuscular (e.g. stroke, multiple&#xD;
             sclerosis, ALS), or patient shows evidence of dysphagia when the 'safety test' capsule&#xD;
             is administered&#xD;
&#xD;
          -  History of aspiration&#xD;
&#xD;
          -  History of gastroparesis&#xD;
&#xD;
          -  History of intestinal obstruction&#xD;
&#xD;
          -  Severe food allergy (e.g. anaphylaxis or anaphylactoid reaction) Adverse event&#xD;
             attributable to a previous FMT&#xD;
&#xD;
          -  Patients with allergies to sodium chloride, glycerol, theobroma oil, hide bovine&#xD;
             gelatin, sodium lauryl sulfate, Food, Drugs &amp; Cosmetics certified colorants (FD&amp;C), or&#xD;
             titanium dioxide, all ingredients Generally Recognized As Safe (GRAS)&#xD;
&#xD;
          -  History of ongoing antibiotic use (e.g. nitrofurantoin for urinary tract infection&#xD;
             (UTI) prophylaxis) Currently pregnant or breastfeeding -Any condition for which the&#xD;
             treating physician thinks the treatment may pose a health risk (e.g. severely&#xD;
             immunocompromised)-&#xD;
      </textblock>
    </criteria>
    <gender>All</gender>
    <minimum_age>18 Years</minimum_age>
    <maximum_age>N/A</maximum_age>
    <healthy_volunteers>No</healthy_volunteers>
  </eligibility>
  <overall_official>
    <last_name>Tamar Barlam, MD MSC</last_name>
    <role>Principal Investigator</role>
    <affiliation>Boston Medical Center</affiliation>
  </overall_official>
  <location>
    <facility>
      <name>Boston Medical Center</name>
      <address>
        <city>Boston</city>
        <state>Massachusetts</state>
        <zip>02118</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location_countries>
    <country>United States</country>
  </location_countries>
  <verification_date>November 2021</verification_date>
  <study_first_submitted>November 21, 2018</study_first_submitted>
  <study_first_submitted_qc>January 3, 2019</study_first_submitted_qc>
  <study_first_posted type="Actual">January 7, 2019</study_first_posted>
  <results_first_submitted>November 16, 2021</results_first_submitted>
  <results_first_submitted_qc>November 16, 2021</results_first_submitted_qc>
  <results_first_posted type="Actual">December 15, 2021</results_first_posted>
  <last_update_submitted>November 16, 2021</last_update_submitted>
  <last_update_submitted_qc>November 16, 2021</last_update_submitted_qc>
  <last_update_posted type="Actual">December 15, 2021</last_update_posted>
  <responsible_party>
    <responsible_party_type>Sponsor</responsible_party_type>
  </responsible_party>
  <keyword>Fecal Microbiota Transplant (FMT)</keyword>
  <keyword>Vancomycin</keyword>
  <keyword>Dysbiosis</keyword>
  <keyword>fecal microbiome</keyword>
  <keyword>C difficile infection</keyword>
  <condition_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Infections</mesh_term>
    <mesh_term>Clostridium Infections</mesh_term>
  </condition_browse>
  <intervention_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Vancomycin</mesh_term>
  </intervention_browse>
  <patient_data>
    <sharing_ipd>No</sharing_ipd>
  </patient_data>
  <provided_document_section>
    <provided_document>
      <document_type>Study Protocol and Statistical Analysis Plan</document_type>
      <document_has_protocol>Yes</document_has_protocol>
      <document_has_icf>No</document_has_icf>
      <document_has_sap>Yes</document_has_sap>
      <document_date>February 18, 2020</document_date>
      <document_url>https://ClinicalTrials.gov/ProvidedDocs/33/NCT03795233/Prot_SAP_000.pdf</document_url>
    </provided_document>
  </provided_document_section>

  <clinical_results>

    <participant_flow>
      <group_list>
        <group group_id="P1">
          <title>Fecal Microbiota Transplantation</title>
          <description>Fecal microbiota transplant (FMT) G3 capsules will be administered after standard of care with oral vancomycin therapy in participants with primary Clostridium difficile infection.&#xD;
Fecal microbiota transplant G3 capsules: After standard of care therapy with oral vancomycin, frozen oral FMT capsules will be provided in a formulation designed to deliver the product to the large intestine. 30 FMT capsules will be administered over a 2 hour period under direct observation</description>
        </group>
        <group group_id="P2">
          <title>Oral Vancomycin Alone (Control)</title>
          <description>Oral vancomycin therapy will be administered as per standard of care in participants with primary clostridium difficile infection.&#xD;
Oral Vancomycin alone: Standard of care will be provided with oral vancomycin therapy.</description>
        </group>
      </group_list>
      <period_list>
        <period>
          <title>Overall Study</title>
          <milestone_list>
            <milestone>
              <title>STARTED</title>
              <participants_list>
                <participants group_id="P1" count="4"/>
                <participants group_id="P2" count="1"/>
              </participants_list>
            </milestone>
            <milestone>
              <title>COMPLETED</title>
              <participants_list>
                <participants group_id="P1" count="0"/>
                <participants group_id="P2" count="0"/>
              </participants_list>
            </milestone>
            <milestone>
              <title>NOT COMPLETED</title>
              <participants_list>
                <participants group_id="P1" count="4"/>
                <participants group_id="P2" count="1"/>
              </participants_list>
            </milestone>
          </milestone_list>
          <drop_withdraw_reason_list>
            <drop_withdraw_reason>
              <title>Withdrawal by Subject</title>
              <participants_list>
                <participants group_id="P1" count="2"/>
                <participants group_id="P2" count="1"/>
              </participants_list>
            </drop_withdraw_reason>
            <drop_withdraw_reason>
              <title>Lost to Follow-up</title>
              <participants_list>
                <participants group_id="P1" count="1"/>
                <participants group_id="P2" count="0"/>
              </participants_list>
            </drop_withdraw_reason>
            <drop_withdraw_reason>
              <title>Death</title>
              <participants_list>
                <participants group_id="P1" count="1"/>
                <participants group_id="P2" count="0"/>
              </participants_list>
            </drop_withdraw_reason>
          </drop_withdraw_reason_list>
        </period>
      </period_list>
    </participant_flow>

    <baseline>
      <group_list>
        <group group_id="B1">
          <title>Fecal Microbiota Transplantation</title>
          <description>Fecal microbiota transplant G3 capsules will be administered after standard of care with oral vancomycin therapy in participants with primary Clostridium difficile infection.&#xD;
Fecal microbiota transplant G3 capsules: After standard of care therapy with oral vancomycin, frozen oral FMT capsules will be provided in a formulation designed to deliver the product to the large intestine. 30 FMT capsules will be administered over a 2 hour period under direct observation</description>
        </group>
        <group group_id="B2">
          <title>Oral Vancomycin Alone (Control)</title>
          <description>Oral vancomycin therapy will be administered as per standard of care in participants with primary clostridium difficile infection.&#xD;
Oral Vancomycin alone: Standard of care will be provided with oral vancomycin therapy.</description>
        </group>
        <group group_id="B3">
          <title>Total</title>
          <description>Total of all reporting groups</description>
        </group>
      </group_list>
      <analyzed_list>
        <analyzed>
          <units>Participants</units>
          <scope>Overall</scope>
          <count_list>
            <count group_id="B1" value="4"/>
            <count group_id="B2" value="1"/>
            <count group_id="B3" value="5"/>
          </count_list>
        </analyzed>
      </analyzed_list>
      <measure_list>
        <measure>
          <title>Age</title>
          <units>Participants</units>
          <param>Count of Participants</param>
          <class_list>
            <class>
              <category_list>
                <category>
                  <title>&lt;=18 years</title>
                  <measurement_list>
                    <measurement group_id="B1" value="0"/>
                    <measurement group_id="B2" value="0"/>
                    <measurement group_id="B3" value="0"/>
                  </measurement_list>
                </category>
                <category>
                  <title>Between 18 and 65 years</title>
                  <measurement_list>
                    <measurement group_id="B1" value="4"/>
                    <measurement group_id="B2" value="1"/>
                    <measurement group_id="B3" value="5"/>
                  </measurement_list>
                </category>
                <category>
                  <title>&gt;=65 years</title>
                  <measurement_list>
                    <measurement group_id="B1" value="0"/>
                    <measurement group_id="B2" value="0"/>
                    <measurement group_id="B3" value="0"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
        <measure>
          <title>Age</title>
          <units>years</units>
          <param>Mean</param>
          <dispersion>Standard Deviation</dispersion>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="B1" value="49.8" spread="11.9"/>
                    <measurement group_id="B2" value="58"/>
                    <measurement group_id="B3" value="51.4" spread="10.9"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
        <measure>
          <title>Sex: Female, Male</title>
          <units>Participants</units>
          <param>Count of Participants</param>
          <class_list>
            <class>
              <category_list>
                <category>
                  <title>Female</title>
                  <measurement_list>
                    <measurement group_id="B1" value="2"/>
                    <measurement group_id="B2" value="0"/>
                    <measurement group_id="B3" value="2"/>
                  </measurement_list>
                </category>
                <category>
                  <title>Male</title>
                  <measurement_list>
                    <measurement group_id="B1" value="2"/>
                    <measurement group_id="B2" value="1"/>
                    <measurement group_id="B3" value="3"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
        <measure>
          <title>Race/Ethnicity, Customized</title>
          <units>Participants</units>
          <param>Count of Participants</param>
          <class_list>
            <class>
              <title>Black or African Am</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="B1" value="2"/>
                    <measurement group_id="B2" value="0"/>
                    <measurement group_id="B3" value="2"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>White</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="B1" value="2"/>
                    <measurement group_id="B2" value="1"/>
                    <measurement group_id="B3" value="3"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
        <measure>
          <title>Region of Enrollment</title>
          <units>participants</units>
          <param>Number</param>
          <class_list>
            <class>
              <title>United States</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="B1" value="4"/>
                    <measurement group_id="B2" value="1"/>
                    <measurement group_id="B3" value="5"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </measure_list>
    </baseline>

    <outcome_list>
      <outcome>
        <type>Primary</type>
        <title>Stool Microbiome With and Without FMT Administration</title>
        <description>The stool microbiome in participants who receive additional FMT at end of Clostridium difficile infection (CDI) treatment with oral vancomycin will be compared to the stool microbiome in participants with standard treatment or oral vancomycin alone</description>
        <time_frame>11 months</time_frame>
        <population>This outcome measure was not obtained on any of the participants as no participant was in the study at 11 months.</population>
        <group_list>
          <group group_id="O1">
            <title>Fecal Microbiota Transplantation</title>
            <description>Fecal microbiota transplant G3 capsules will be administered after standard of care with oral vancomycin therapy in participants with primary Clostridium difficile infection.&#xD;
Fecal microbiota transplant G3 capsules: After standard of care therapy with oral vancomycin, frozen oral FMT capsules will be provided in a formulation designed to deliver the product to the large intestine. 30 FMT capsules will be administered over a 2 hour period under direct observation</description>
          </group>
          <group group_id="O2">
            <title>Oral Vancomycin Alone (Control)</title>
            <description>Oral vancomycin therapy will be administered as per standard of care in participants with primary clostridium difficile infection.&#xD;
Oral Vancomycin alone: Standard of care will be provided with oral vancomycin therapy.</description>
          </group>
        </group_list>
        <measure>
          <title>Stool Microbiome With and Without FMT Administration</title>
          <description>The stool microbiome in participants who receive additional FMT at end of Clostridium difficile infection (CDI) treatment with oral vancomycin will be compared to the stool microbiome in participants with standard treatment or oral vancomycin alone</description>
          <population>This outcome measure was not obtained on any of the participants as no participant was in the study at 11 months.</population>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="0"/>
                <count group_id="O2" value="0"/>
              </count_list>
            </analyzed>
          </analyzed_list>
        </measure>
      </outcome>
      <outcome>
        <type>Secondary</type>
        <title>Feasibility of Administering FMT After Completion of a Course of Oral Vancomycin Therapy</title>
        <description>The number and proportion of FMT pills participants ingest after completion of a course of oral vancomycin therapy will be documented.</description>
        <time_frame>12 months</time_frame>
        <population>This outcome measure was not obtained on any of the participants as no participant was in the study at 12 months.</population>
        <group_list>
          <group group_id="O1">
            <title>Fecal Microbiota Transplantation</title>
            <description>Fecal microbiota transplant G3 capsules will be administered after standard of care with oral vancomycin therapy in participants with primary Clostridium difficile infection.&#xD;
Fecal microbiota transplant G3 capsules: After standard of care therapy with oral vancomycin, frozen oral FMT capsules will be provided in a formulation designed to deliver the product to the large intestine. 30 FMT capsules will be administered over a 2 hour period under direct observation</description>
          </group>
          <group group_id="O2">
            <title>Oral Vancomycin Alone (Control)</title>
            <description>Oral vancomycin therapy will be administered as per standard of care in participants with primary clostridium difficile infection.&#xD;
Oral Vancomycin alone: Standard of care will be provided with oral vancomycin therapy.</description>
          </group>
        </group_list>
        <measure>
          <title>Feasibility of Administering FMT After Completion of a Course of Oral Vancomycin Therapy</title>
          <description>The number and proportion of FMT pills participants ingest after completion of a course of oral vancomycin therapy will be documented.</description>
          <population>This outcome measure was not obtained on any of the participants as no participant was in the study at 12 months.</population>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="0"/>
                <count group_id="O2" value="0"/>
              </count_list>
            </analyzed>
          </analyzed_list>
        </measure>
      </outcome>
      <outcome>
        <type>Secondary</type>
        <title>Incidence of Treatment-Emergent Adverse Events [Safety and Tolerability] of FMT After a Course of Oral Vancomycin Therapy</title>
        <description>Study participants will be monitored for any adverse events to FMT such as nausea or vomiting, abdominal pain or diarrhea.</description>
        <time_frame>During test dose, during 90 minutes of FMT administration, 30 minutes after FMT administration, 48-72 hours after FMT administration</time_frame>
        <population>Only one participant in the FMT arm ingested the intervention.</population>
        <group_list>
          <group group_id="O1">
            <title>Fecal Microbiota Transplantation</title>
            <description>Fecal microbiota transplant G3 capsules will be administered after standard of care with oral vancomycin therapy in participants with primary Clostridium difficile infection.&#xD;
Fecal microbiota transplant G3 capsules: After standard of care therapy with oral vancomycin, frozen oral FMT capsules will be provided in a formulation designed to deliver the product to the large intestine. 30 FMT capsules will be administered over a 2 hour period under direct observation</description>
          </group>
          <group group_id="O2">
            <title>Oral Vancomycin Alone (Control)</title>
            <description>Oral vancomycin therapy will be administered as per standard of care in participants with primary clostridium difficile infection.&#xD;
Oral Vancomycin alone: Standard of care will be provided with oral vancomycin therapy.</description>
          </group>
        </group_list>
        <measure>
          <title>Incidence of Treatment-Emergent Adverse Events [Safety and Tolerability] of FMT After a Course of Oral Vancomycin Therapy</title>
          <description>Study participants will be monitored for any adverse events to FMT such as nausea or vomiting, abdominal pain or diarrhea.</description>
          <population>Only one participant in the FMT arm ingested the intervention.</population>
          <units>Participants</units>
          <param>Count of Participants</param>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="1"/>
                <count group_id="O2" value="0"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="0"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </outcome>
      <outcome>
        <type>Secondary</type>
        <title>Incidence of Gastrointestinal Symptomatology Based on a Survey After CDI</title>
        <description>A detailed survey with 15 questions will be administered on GI symptoms Physicians will go over any significant adverse events to determine if they are related, possibly related or unrelated to oral FMT administration</description>
        <time_frame>60 days</time_frame>
        <population>This outcome measure was not obtained on any of the participants.</population>
        <group_list>
          <group group_id="O1">
            <title>Fecal Microbiota Transplantation</title>
            <description>Fecal microbiota transplant G3 capsules will be administered after standard of care with oral vancomycin therapy in participants with primary Clostridium difficile infection.&#xD;
Fecal microbiota transplant G3 capsules: After standard of care therapy with oral vancomycin, frozen oral FMT capsules will be provided in a formulation designed to deliver the product to the large intestine. 30 FMT capsules will be administered over a 2 hour period under direct observation</description>
          </group>
          <group group_id="O2">
            <title>Oral Vancomycin Alone (Control)</title>
            <description>Oral vancomycin therapy will be administered as per standard of care in participants with primary clostridium difficile infection.&#xD;
Oral Vancomycin alone: Standard of care will be provided with oral vancomycin therapy.</description>
          </group>
        </group_list>
        <measure>
          <title>Incidence of Gastrointestinal Symptomatology Based on a Survey After CDI</title>
          <description>A detailed survey with 15 questions will be administered on GI symptoms Physicians will go over any significant adverse events to determine if they are related, possibly related or unrelated to oral FMT administration</description>
          <population>This outcome measure was not obtained on any of the participants.</population>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="0"/>
                <count group_id="O2" value="0"/>
              </count_list>
            </analyzed>
          </analyzed_list>
        </measure>
      </outcome>
      <outcome>
        <type>Secondary</type>
        <title>CDI Recurrence</title>
        <description>Patients will be monitored for recurrent C difficile infection defined as non-resolution or recurrence of GI symptoms (abdominal pain, diarrhea etc) and/or a positive stool C difficile test The proportion of participants with CDI recurrence will be documented.</description>
        <time_frame>60 days</time_frame>
        <population>This outcome measure was not obtained on any of the participants.</population>
        <group_list>
          <group group_id="O1">
            <title>Fecal Microbiota Transplantation</title>
            <description>Fecal microbiota transplant G3 capsules will be administered after standard of care with oral vancomycin therapy in participants with primary Clostridium difficile infection.&#xD;
Fecal microbiota transplant G3 capsules: After standard of care therapy with oral vancomycin, frozen oral FMT capsules will be provided in a formulation designed to deliver the product to the large intestine. 30 FMT capsules will be administered over a 2 hour period under direct observation</description>
          </group>
          <group group_id="O2">
            <title>Oral Vancomycin Alone (Control)</title>
            <description>Oral vancomycin therapy will be administered as per standard of care in participants with primary clostridium difficile infection.&#xD;
Oral Vancomycin alone: Standard of care will be provided with oral vancomycin therapy.</description>
          </group>
        </group_list>
        <measure>
          <title>CDI Recurrence</title>
          <description>Patients will be monitored for recurrent C difficile infection defined as non-resolution or recurrence of GI symptoms (abdominal pain, diarrhea etc) and/or a positive stool C difficile test The proportion of participants with CDI recurrence will be documented.</description>
          <population>This outcome measure was not obtained on any of the participants.</population>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="0"/>
                <count group_id="O2" value="0"/>
              </count_list>
            </analyzed>
          </analyzed_list>
        </measure>
      </outcome>
      <outcome>
        <type>Secondary</type>
        <title>Number of Hospital Readmissions After Treatment</title>
        <description>The number of hospital readmissions within 30 days after CDI treatment per patient history and chart review will be obtained</description>
        <time_frame>30 days</time_frame>
        <population>This outcome measure was not obtained on any of the participants.</population>
        <group_list>
          <group group_id="O1">
            <title>Fecal Microbiota Transplantation</title>
            <description>Fecal microbiota transplant G3 capsules will be administered after standard of care with oral vancomycin therapy in participants with primary Clostridium difficile infection.&#xD;
Fecal microbiota transplant G3 capsules: After standard of care therapy with oral vancomycin, frozen oral FMT capsules will be provided in a formulation designed to deliver the product to the large intestine. 30 FMT capsules will be administered over a 2 hour period under direct observation</description>
          </group>
          <group group_id="O2">
            <title>Oral Vancomycin Alone (Control)</title>
            <description>Oral vancomycin therapy will be administered as per standard of care in participants with primary clostridium difficile infection.&#xD;
Oral Vancomycin alone: Standard of care will be provided with oral vancomycin therapy.</description>
          </group>
        </group_list>
        <measure>
          <title>Number of Hospital Readmissions After Treatment</title>
          <description>The number of hospital readmissions within 30 days after CDI treatment per patient history and chart review will be obtained</description>
          <population>This outcome measure was not obtained on any of the participants.</population>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="0"/>
                <count group_id="O2" value="0"/>
              </count_list>
            </analyzed>
          </analyzed_list>
        </measure>
      </outcome>
    </outcome_list>

    <reported_events>
      <time_frame>6 months</time_frame>
      <group_list>
        <group group_id="E1">
          <title>Fecal Microbiota Transplantation</title>
          <description>Fecal microbiota transplant G3 capsules will be administered after standard of care with oral vancomycin therapy in participants with primary Clostridium difficile infection.&#xD;
Fecal microbiota transplant G3 capsules: After standard of care therapy with oral vancomycin, frozen oral FMT capsules will be provided in a formulation designed to deliver the product to the large intestine. 30 FMT capsules will be administered over a 2 hour period under direct observation</description>
        </group>
        <group group_id="E2">
          <title>Oral Vancomycin Alone (Control)</title>
          <description>Oral vancomycin therapy will be administered as per standard of care in participants with primary clostridium difficile infection.&#xD;
Oral Vancomycin alone: Standard of care will be provided with oral vancomycin therapy.</description>
        </group>
      </group_list>
      <serious_events>
        <category_list>
          <category>
            <title>Total</title>
            <event_list>
              <event>
                <sub_title>Total, all-cause mortality</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="4"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="1"/>
              </event>
              <event>
                <sub_title>Total, serious adverse events</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="4"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="1"/>
              </event>
            </event_list>
          </category>
        </category_list>
      </serious_events>
      <other_events>
        <frequency_threshold>0</frequency_threshold>
        <category_list>
          <category>
            <title>Total</title>
            <event_list>
              <event>
                <sub_title>Total, other adverse events</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="4"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="1"/>
              </event>
            </event_list>
          </category>
        </category_list>
      </other_events>
    </reported_events>

    <certain_agreements>
      <pi_employee>All Principal Investigators ARE employed by the organization sponsoring the study.</pi_employee>
      <restrictive_agreement>There is NOT an agreement between Principal Investigators and the Sponsor (or its agents) that restricts the PI's rights to discuss or publish trial results after the trial is completed. </restrictive_agreement>
    </certain_agreements>
    <limitations_and_caveats>The study was terminated after a covid-related suspension and the unavailability of drug. Data were not collected for 5 of the 6 outcomes measures and no data were collected for the primary outcome measure as no participant was in the study at the timeframe of 11 months.</limitations_and_caveats>
    <point_of_contact>
      <name_or_title>Tamar Barlam, MD MSC</name_or_title>
      <organization>Boston Medical Center</organization>
      <phone>617 414 5190</phone>
      <email>tamar.barlam@bmc.org</email>
    </point_of_contact>
  </clinical_results>
</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/NCT03795233
org study id: H-37574
nct id: NCT03795233
lead sponsor: 
has dmc: Yes
is fda regulated drug: Yes
is fda regulated device: No
Clostridium difficile infection (CDI) is one of the most urgent health threats in the U.S.
      associated with antibiotic use. After an initial episode, disease recurrence is high and
      relapses can occur in 20-30% of people treated with oral vancomycin. An antibiotic course can
      affect the gut microbiome for years, and patients with CDI have additional dysbiosis of their
      gut flora. Oral vancomycin perturbs the gut microbiome further. Restoration of the microbiome
      with Fecal Microbiota Transplant (FMT) has been proven a highly efficacious and
      cost-effective treatment for recurrent CDI. FMT has had very limited study for a primary
      episode of CDI to date because an endoscopic procedure was the recommended route of delivery.
      However, FMT is now available via frozen oral capsules and has been shown to be non-inferior
      to FMT via colonoscopy in randomized controlled trials.

      The investigators hypothesize that outcomes after a first episode of CDI can be improved if
      the microbiome is restored with oral FMT. It is further hypothesized that this will
      compensate for any additional microbiome perturbation caused by administration of oral
      vancomycin and decrease the likelihood of recurrence. Because the hypothesis is based on
      restoration of the microbiome, the investigators propose this proof-of-concept pilot study to
      examine whether FMT administered after oral vancomycin therapy for primary CDI restores
      microbiome diversity compared to patients who do not receive FMT. Because of the potential
      health benefits, this approach deserves further study. The results from this pilot study on
      the microbiome diversity as well as the surveys to be conducted about GI symptomatology
      (e.g., diarrhea, abdominal pain, bloating), CDI recurrence and healthcare utilization, would
      provide preliminary data to support a randomized controlled, multicenter clinical trial.
Population: Patients >= 18 years hospitalized at Boston Medical Center (BMC) with a first
      documented episode of CDI.

      Intervention: 30 FMT capsules administered orally under direct observation within 7 days of
      completion of 10-14 day treatment of oral vancomycin for CDI.

      Objectives:

        1. To characterize the microbial diversity in stool samples from subjects with a primary
           episode of CDI before and after oral vancomycin and determine the impact of FMT after
           completion of oral vancomycin course.

        2. To characterize the feasibility and tolerability of FMT after completion of a course of
           oral vancomycin therapy for primary CDI, and to describe 30-day hospital readmission and
           gastrointestinal symptomatology and/or CDI recurrence during 60-day follow-up.

      Design/Methodology:

      15 subjects will be enrolled who are hospitalized at BMC for a primary episode of CDI. A
      discard aliquot from baseline stool samples obtained clinically for diagnosis will be frozen.
      Subjects will receive the standard of care treatment (oral vancomycin for 10-14 days) and
      within 7 days following completion will receive oral FMT during a 2 hour visit in the
      Infectious Disease (ID) Clinical Trials Unit. An additional 5 subjects will be enrolled as
      controls. Stool samples will be collected at time of CDI diagnosis and again 3 weeks after
      FMT for intervention group and 4 weeks after completion of oral vancomycin treatment for
      control subjects. The post-treatment samples will be obtained by the patient using special
      stool sample collection kits known as RNAlater kits (ribonucleic acid stabilization). These
      contain a liquid nontoxic tissue storage reagent known as RNAlater and helps preserve the
      stool sample. The subjects will mail this stool sample to the BMC Clinical Trials Unit (CTU)
      where it will aliquoted, centrifuged and frozen.

      Samples will be processed at a collaborating lab at Tufts to characterize the fecal
      microbiome pre- and post oral FMT.

      Study personnel will contact participants via telephone 60 days after FMT dosing to
      administer a follow-up survey (including questions on residual symptoms. CDI recurrence,
      re-hospitalization, adverse events and FMT acceptability).

      Total Study Duration: Anticipated time: 12 months

      Subject Participation Duration: The researchers anticipate a period of 1-2 hours while an
      inpatient for the screening and consent process, 2 hours for the CTU visit for FMT and 20-30
      minutes responding to a follow up telephone survey. Total time in the study from enrollment
      to completion of follow-up will be approximately 3 months and will include 10-14 days of CDI
      treatment with oral vancomycin (per standard of care treatment), the FMT administration and a
      60 day follow up.
allocation: Non-Randomized
intervention model: Parallel Assignment
primary purpose: Treatment
masking: None (Open Label)
measure: Stool Microbiome With and Without FMT Administration
time frame: 11 months
description: The stool microbiome in participants who receive additional FMT at end of Clostridium difficile infection (CDI) treatment with oral vancomycin will be compared to the stool microbiome in participants with standard treatment or oral vancomycin alone
measure: Feasibility of Administering FMT After Completion of a Course of Oral Vancomycin Therapy
time frame: 12 months
description: The number and proportion of FMT pills participants ingest after completion of a course of oral vancomycin therapy will be documented.
measure: Incidence of Treatment-Emergent Adverse Events [Safety and Tolerability] of FMT After a Course of Oral Vancomycin Therapy
time frame: During test dose, during 90 minutes of FMT administration, 30 minutes after FMT administration, 48-72 hours after FMT administration
description: Study participants will be monitored for any adverse events to FMT such as nausea or vomiting, abdominal pain or diarrhea.
measure: Incidence of Gastrointestinal Symptomatology Based on a Survey After CDI
time frame: 60 days
description: A detailed survey with 15 questions will be administered on GI symptoms Physicians will go over any significant adverse events to determine if they are related, possibly related or unrelated to oral FMT administration
measure: CDI Recurrence
time frame: 60 days
description: Patients will be monitored for recurrent C difficile infection defined as non-resolution or recurrence of GI symptoms (abdominal pain, diarrhea etc) and/or a positive stool C difficile test The proportion of participants with CDI recurrence will be documented.
measure: Number of Hospital Readmissions After Treatment
time frame: 30 days
description: The number of hospital readmissions within 30 days after CDI treatment per patient history and chart review will be obtained
arm group label: Fecal microbiota transplantation
arm group type: Experimental
description: Fecal microbiota transplant G3 capsules will be administered after standard of care with oral vancomycin therapy in participants with primary Clostridium difficile infection.
arm group label: Oral vancomycin alone (Control)
arm group type: Active Comparator
description: Oral vancomycin therapy will be administered as per standard of care in participants with primary clostridium difficile infection.
intervention type: Biological
intervention name: Fecal microbiota transplant G3 capsules
description: After standard of care therapy with oral vancomycin, frozen oral FMT capsules will be provided in a formulation designed to deliver the product to the large intestine. 30 FMT capsules will be administered over a 2 hour period under direct observation
arm group label: Fecal microbiota transplantation
other name: FMT
intervention type: Other
intervention name: Oral Vancomycin alone
description: Standard of care will be provided with oral vancomycin therapy.
arm group label: Oral vancomycin alone (Control)
other name: Oral Vancocin alone
criteria: 
gender: All
minimum age: 18 Years
maximum age: N/A
healthy volunteers: No
last name: Tamar Barlam, MD MSC
role: Principal Investigator
affiliation: Boston Medical Center
facility: 
country: United States
responsible party type: Sponsor
mesh term: Infections
mesh term: Clostridium Infections
mesh term: Vancomycin
sharing ipd: No
provided document: 
participant flow: 
baseline: 
outcome list: 
reported events: 
certain agreements: 
limitations and caveats: The study was terminated after a covid-related suspension and the unavailability of drug. Data were not collected for 5 of the 6 outcomes measures and no data were collected for the primary outcome measure as no participant was in the study at the timeframe of 11 months.
point of contact: 