<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/NCT03755765</url>
  </required_header>
  <id_info>
    <org_study_id>2018-0736</org_study_id>
    <secondary_id>1R61AT009622-01A1</secondary_id>
    <nct_id>NCT03755765</nct_id>
  </id_info>
  <brief_title>Mechanisms of Preventing Antibiotic-Associated Diarrhea and the Role for Probiotics</brief_title>
  <acronym>YOBIOTIC</acronym>
  <official_title>Exploratory Pilot Studies to Demonstrate Mechanisms of Preventing Antibiotic-Associated Diarrhea and the Role for Probiotics</official_title>
  <sponsors>
    <lead_sponsor>
      <agency>Georgetown University</agency>
      <agency_class>Other</agency_class>
    </lead_sponsor>
    <collaborator>
      <agency>National Center for Complementary and Integrative Health (NCCIH)</agency>
      <agency_class>NIH</agency_class>
    </collaborator>
    <collaborator>
      <agency>University of Maryland, Baltimore</agency>
      <agency_class>Other</agency_class>
    </collaborator>
  </sponsors>
  <source>Georgetown University</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>
      The focus of the study is to better understand the mechanisms causing antibiotic-associated&#xD;
      diarrhea (AAD) and how probiotics may prevent some of the iatrogenic effects of antibiotic&#xD;
      medications. One of the most common indications for probiotics is for prevention of&#xD;
      antibiotic-associated diarrhea. Clinically, different probiotic strains have demonstrated the&#xD;
      ability to prevent AAD; however, the mechanism of action behind this effect has not been&#xD;
      elucidated. Data from several studies suggest that antibiotic-induced disruption of commensal&#xD;
      bacteria in the colon results in a significant (up to 50%) reduction in short chain fatty&#xD;
      acid (SCFA) production and a concomitant reduction in Na-dependent fluid absorption resulting&#xD;
      in AAD. Probiotics have been shown to ameliorate a variety of gastrointestinal disease states&#xD;
      and thus, the study investigators hypothesize that administration of a probiotic yogurt will&#xD;
      protect against the development of AAD.&#xD;
    </textblock>
  </brief_summary>
  <detailed_description>
    <textblock>
      Probiotics are live microorganisms that, when administered in adequate amounts, confer a&#xD;
      health benefit on the host. One of the most common indications for probiotic treatment is the&#xD;
      prevention of antibiotic-associated diarrhea (AAD). Unfortunately, the efficacy of many&#xD;
      probiotic products used for AAD is not supported by rigorous independent research, and&#xD;
      non-evidence-based clinical usage is common. Data from several studies are consistent with&#xD;
      the notion that antibiotic-induced disruption of commensal bacteria in the colon results in a&#xD;
      significant reduction of short chain fatty acid (SCFA) production and a concomitant reduction&#xD;
      in Na-dependent fluid absorption resulting in AAD. The probiotic strain being studied,&#xD;
      Bifidobacterium animalis subsp. lactis BB-12 (BB-12), has been shown to ameliorate a variety&#xD;
      of gastrointestinal disease states and is known to produce acetate at concentrations up to 50&#xD;
      mM in vitro. Thus, the investigators hypothesize that administration of BB-12 at the same&#xD;
      time as antibiotic consumption will protect against the development of AAD through its&#xD;
      ability to generate acetate directly, and also increase other SCFAs through cross-feeding of&#xD;
      certain bacteria in the Firmicutes phylum such Clostridium, Eubacterium and Roseburia, which&#xD;
      use acetate to produce butyrate.&#xD;
&#xD;
      The primary aim of the R61 phase (N=60) is to determine the ability of BB-12 to impact&#xD;
      antibiotic-induced reduction in SCFA as reflected by the levels of acetate, the most abundant&#xD;
      primary colonic SCFA. The primary hypothesis is that antibiotics will result in a reduction&#xD;
      in fecal SCFA, but BB-12 supplementation will protect against antibiotic-induced SCFA&#xD;
      reduction and/or be associated with a more rapid return to baseline SCFA levels as compared&#xD;
      to controls. Antibiotics also result in a decrease in total microbial counts and diversity in&#xD;
      the gut microbiota, disrupting the homeostasis of the gut ecosystem and allowing colonization&#xD;
      by pathogens. The secondary aim will be to determine the ability of BB-12 to impact&#xD;
      antibiotic-induced disruption of the gut microbiota with 16S (16 Svedberg) ribosomal&#xD;
      ribonucleic acid (rRNA) profiling. The secondary hypothesis is that antibiotics will result&#xD;
      in a decrease in the overall number and diversity of bacterial species present in the fecal&#xD;
      microbiota, and further BB-12 supplementation will protect against antibiotic-induced shifts&#xD;
      in the microbiota and/or will be associated with a more rapid return to a baseline microbiota&#xD;
      composition as compared to controls. The long-term goal is to determine the impact of BB-12&#xD;
      on a variety of gastrointestinal disease states and ages, through high-level independent&#xD;
      research. This mechanism elucidation is important for directing future translational and&#xD;
      effectiveness research.&#xD;
    </textblock>
  </detailed_description>
  <overall_status>Completed</overall_status>
  <start_date type="Actual">July 23, 2019</start_date>
  <completion_date type="Actual">January 8, 2020</completion_date>
  <primary_completion_date type="Actual">January 8, 2020</primary_completion_date>
  <phase>Early Phase 1</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>Other</primary_purpose>
    <masking>Triple (Participant, Investigator, Outcomes Assessor)</masking>
  </study_design_info>
  <primary_outcome>
    <measure>Level of Fecal Short-chain Fatty Acid (SCFA) Acetate</measure>
    <time_frame>day 0 (post run-in), 7, 14, 21, 30</time_frame>
    <description>Level of fecal short-chain fatty acid acetate (SCFA) after administration of amoxicillin clavulanate</description>
  </primary_outcome>
  <secondary_outcome>
    <measure>Level of Fecal SCFA Propionate</measure>
    <time_frame>day 0 (post run-in), 7, 14, 21, 30</time_frame>
    <description>Level of fecal short-chain fatty acid propionate after administration of amoxicillin clavulanate</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Level of Fecal SCFA Butyrate</measure>
    <time_frame>day 0 (post run-in), 7, 14, 21, 30</time_frame>
    <description>Level of fecal short-chain fatty acid butyrate (μM) after administration of amoxicillin clavulanate</description>
  </secondary_outcome>
  <other_outcome>
    <measure>Change in Community Diversity (Shannon Diversity Index) From Pre run-in Baseline</measure>
    <time_frame>day 0 (pre run-in), 7, 14, 21, 30</time_frame>
    <description>The Shannon diversity metric is a measure of community diversity and takes into account species richness (number of distinct taxa) and the relative abundance of each taxon. The Shannon diversity index was calculated for samples at each time point from subjects receiving control or BB-12 yogurt. The first of two baseline samples was collected from each subject at the time of enrollment (pre run-in) before a 30-day run-in period in which the consumption of dietary probiotics was stopped. A higher index indicates more diversity and a lower index indicates less diversity.</description>
  </other_outcome>
  <other_outcome>
    <measure>Change in Community Diversity (Shannon Diversity Index) From Post run-in Baseline</measure>
    <time_frame>day 0 (post run-in), 7, 14, 21, 30</time_frame>
    <description>The Shannon diversity metric is a measure of community diversity and takes into account species richness (number of distinct taxa) and the relative abundance of each taxon. The Shannon diversity index was calculated for samples at each time point from subjects receiving control or BB-12 yogurt. The second baseline sample was collected from each subject after a 30-day run-in period in which the consumption of dietary probiotics was stopped (post run-in). A higher index indicates more diversity and a lower index indicates less diversity.</description>
  </other_outcome>
  <other_outcome>
    <measure>Bray-Curtis Dissimilarity</measure>
    <time_frame>day 0, 7, 14, 21, 30</time_frame>
    <description>Community divergence over time with respect to the baseline sample (post run-in, day 0)</description>
  </other_outcome>
  <other_outcome>
    <measure>Change in Diarrhea/Stool Frequency</measure>
    <time_frame>day 7, 14, 21, 30</time_frame>
    <description>Change in diarrhea/stool frequency from baseline</description>
  </other_outcome>
  <number_of_arms>2</number_of_arms>
  <enrollment type="Actual">66</enrollment>
  <condition>Antibiotic-associated Diarrhea</condition>
  <arm_group>
    <arm_group_label>Control</arm_group_label>
    <arm_group_type>Placebo Comparator</arm_group_type>
    <description>Yogurt without Bifidobacterium animalis subsp. lactis BB-12 (BB-12) and Amoxicillin-Clavulanate 875 Mg-125 Mg Oral Tablet</description>
  </arm_group>
  <arm_group>
    <arm_group_label>BB-12</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>Bifidobacterium animalis subsp. lactis BB-12 (BB-12)-supplemented yogurt and Amoxicillin-Clavulanate 875 Mg-125 Mg Oral Tablet</description>
  </arm_group>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>Amoxicillin-Clavulanate 875 Mg-125 Mg Oral Tablet</intervention_name>
    <description>Amoxicillin-Clavulanate 875 Mg-125 Mg Oral Tablet</description>
    <arm_group_label>BB-12</arm_group_label>
    <arm_group_label>Control</arm_group_label>
    <other_name>Augmentin</other_name>
  </intervention>
  <intervention>
    <intervention_type>Biological</intervention_type>
    <intervention_name>BB-12</intervention_name>
    <description>Bifidobacterium animalis subsp. lactis BB-12-supplemented yogurt</description>
    <arm_group_label>BB-12</arm_group_label>
  </intervention>
  <intervention>
    <intervention_type>Other</intervention_type>
    <intervention_name>Control</intervention_name>
    <description>Yogurt without Bifidobacterium animalis subsp. lactis BB-12 (BB-12)</description>
    <arm_group_label>Control</arm_group_label>
  </intervention>
  <eligibility>
    <criteria>
      <textblock>
        Inclusion Criteria:&#xD;
&#xD;
          1. Has the ability to read, speak, and write in English&#xD;
&#xD;
          2. Has refrigerator (for proper storage of the study yogurt)&#xD;
&#xD;
          3. Has reliable telephone access&#xD;
&#xD;
          4. Is between ages of 18-65 years&#xD;
&#xD;
          5. Agree to refrain from eating yogurts, yogurt drinks, and other foods specified in the&#xD;
             provided What Not to Eat list&#xD;
&#xD;
          6. Agree to collect stool samples and participate in follow-up calls as specified&#xD;
&#xD;
        Exclusion Criteria:&#xD;
&#xD;
          1. Diabetes or asthma that requires medication&#xD;
&#xD;
          2. Allergy to strawberry&#xD;
&#xD;
          3. Active diarrhea (three or more loose stools per day for two consecutive days)&#xD;
&#xD;
          4. Any gastrointestinal (or digestive tract) medications, i.e. medicines for irritable&#xD;
             bowel syndrome, gastroesophageal (acid) reflux disease, inflammatory bowel disease,&#xD;
             etc.&#xD;
&#xD;
          5. History of heart disease, including valvulopathies or cardiac surgery, any implantable&#xD;
             device or prosthetic&#xD;
&#xD;
          6. History of gastrointestinal surgery or disease&#xD;
&#xD;
          7. Lactose intolerance that prevents participant from eating yogurt&#xD;
&#xD;
          8. Allergy to milk-protein&#xD;
&#xD;
          9. Allergy to any component of the product or the yogurt vehicle&#xD;
&#xD;
         10. Allergy to penicillin or cephalosporin class antibiotics&#xD;
&#xD;
         11. Allergy to any of the following medications: a) Penicillin; b) Erythromycin; c)&#xD;
             Tetracycline; d) Trimethoprim; e) Ciprofloxacin&#xD;
&#xD;
         12. Women who are breastfeeding, pregnant, or planning to become pregnant during the study&#xD;
      </textblock>
    </criteria>
    <gender>All</gender>
    <minimum_age>18 Years</minimum_age>
    <maximum_age>65 Years</maximum_age>
    <healthy_volunteers>Accepts Healthy Volunteers</healthy_volunteers>
  </eligibility>
  <overall_official>
    <last_name>Daniel Merenstein, MD</last_name>
    <role>Principal Investigator</role>
    <affiliation>Georgetown University</affiliation>
  </overall_official>
  <overall_official>
    <last_name>Claire Fraser, PhD</last_name>
    <role>Principal Investigator</role>
    <affiliation>University of Maryland, Baltimore</affiliation>
  </overall_official>
  <location>
    <facility>
      <name>Georgetown University Department of Family Medicine</name>
      <address>
        <city>Washington</city>
        <state>District of Columbia</state>
        <zip>20007</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location_countries>
    <country>United States</country>
  </location_countries>
  <results_reference>
    <citation>Merenstein D, Fraser CM, Roberts RF, Liu T, Grant-Beurmann S, Tan TP, Smith KH, Cronin T, Martin OA, Sanders ME, Lucan SC, Kane MA. Bifidobacterium animalis subsp. lactis BB-12 Protects against Antibiotic-Induced Functional and Compositional Changes in Human Fecal Microbiome. Nutrients. 2021 Aug 17;13(8):2814. doi: 10.3390/nu13082814.</citation>
    <PMID>34444974</PMID>
  </results_reference>
  <verification_date>February 2023</verification_date>
  <study_first_submitted>November 18, 2018</study_first_submitted>
  <study_first_submitted_qc>November 26, 2018</study_first_submitted_qc>
  <study_first_posted type="Actual">November 28, 2018</study_first_posted>
  <results_first_submitted>August 3, 2022</results_first_submitted>
  <results_first_submitted_qc>February 15, 2023</results_first_submitted_qc>
  <results_first_posted type="Actual">February 17, 2023</results_first_posted>
  <last_update_submitted>February 15, 2023</last_update_submitted>
  <last_update_submitted_qc>February 15, 2023</last_update_submitted_qc>
  <last_update_posted type="Actual">February 17, 2023</last_update_posted>
  <responsible_party>
    <responsible_party_type>Principal Investigator</responsible_party_type>
    <investigator_affiliation>Georgetown University</investigator_affiliation>
    <investigator_full_name>Daniel Merenstein</investigator_full_name>
    <investigator_title>Director of Research Programs</investigator_title>
  </responsible_party>
  <condition_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Diarrhea</mesh_term>
  </condition_browse>
  <intervention_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Amoxicillin</mesh_term>
    <mesh_term>Clavulanic Acid</mesh_term>
    <mesh_term>Clavulanic Acids</mesh_term>
    <mesh_term>Amoxicillin-Potassium Clavulanate Combination</mesh_term>
  </intervention_browse>
  <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>May 27, 2022</document_date>
      <document_url>https://ClinicalTrials.gov/ProvidedDocs/65/NCT03755765/Prot_SAP_001.pdf</document_url>
    </provided_document>
    <provided_document>
      <document_type>Informed Consent Form</document_type>
      <document_has_protocol>No</document_has_protocol>
      <document_has_icf>Yes</document_has_icf>
      <document_has_sap>No</document_has_sap>
      <document_date>June 22, 2019</document_date>
      <document_url>https://ClinicalTrials.gov/ProvidedDocs/65/NCT03755765/ICF_000.pdf</document_url>
    </provided_document>
  </provided_document_section>

  <clinical_results>

    <participant_flow>
      <group_list>
        <group group_id="P1">
          <title>Control</title>
          <description>Yogurt without Bifidobacterium animalis subsp. lactis BB-12 (BB-12) and Amoxicillin-Clavulanate 875 Mg-125 Mg Oral Tablet&#xD;
Amoxicillin-Clavulanate 875 Mg-125 Mg Oral Tablet: Amoxicillin-Clavulanate 875 Mg-125 Mg Oral Tablet&#xD;
Control: Yogurt without Bifidobacterium animalis subsp. lactis BB-12 (BB-12)</description>
        </group>
        <group group_id="P2">
          <title>BB-12</title>
          <description>Bifidobacterium animalis subsp. lactis BB-12 (BB-12)-supplemented yogurt and Amoxicillin-Clavulanate 875 Mg-125 Mg Oral Tablet&#xD;
Amoxicillin-Clavulanate 875 Mg-125 Mg Oral Tablet: Amoxicillin-Clavulanate 875 Mg-125 Mg Oral Tablet&#xD;
BB-12: Bifidobacterium animalis subsp. lactis BB-12-supplemented yogurt</description>
        </group>
        <group group_id="P3">
          <title>Not Randomized</title>
          <description>Withdrawals prior to randomization</description>
        </group>
      </group_list>
      <period_list>
        <period>
          <title>Overall Study</title>
          <milestone_list>
            <milestone>
              <title>STARTED</title>
              <participants_list>
                <participants group_id="P1" count="20"/>
                <participants group_id="P2" count="42"/>
                <participants group_id="P3" count="4"/>
              </participants_list>
            </milestone>
            <milestone>
              <title>COMPLETED</title>
              <participants_list>
                <participants group_id="P1" count="18"/>
                <participants group_id="P2" count="38"/>
                <participants group_id="P3" count="0"/>
              </participants_list>
            </milestone>
            <milestone>
              <title>NOT COMPLETED</title>
              <participants_list>
                <participants group_id="P1" count="2"/>
                <participants group_id="P2" count="4"/>
                <participants group_id="P3" count="4"/>
              </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="4"/>
                <participants group_id="P3" count="4"/>
              </participants_list>
            </drop_withdraw_reason>
          </drop_withdraw_reason_list>
        </period>
      </period_list>
    </participant_flow>

    <baseline>
      <group_list>
        <group group_id="B1">
          <title>Control</title>
          <description>Yogurt without Bifidobacterium animalis subsp. lactis BB-12 (BB-12) and Amoxicillin-Clavulanate 875 Mg-125 Mg Oral Tablet&#xD;
Amoxicillin-Clavulanate 875 Mg-125 Mg Oral Tablet: Amoxicillin-Clavulanate 875 Mg-125 Mg Oral Tablet&#xD;
Control: Yogurt without Bifidobacterium animalis subsp. lactis BB-12 (BB-12)</description>
        </group>
        <group group_id="B2">
          <title>BB-12</title>
          <description>Bifidobacterium animalis subsp. lactis BB-12 (BB-12)-supplemented yogurt and Amoxicillin-Clavulanate 875 Mg-125 Mg Oral Tablet&#xD;
Amoxicillin-Clavulanate 875 Mg-125 Mg Oral Tablet: Amoxicillin-Clavulanate 875 Mg-125 Mg Oral Tablet&#xD;
BB-12: Bifidobacterium animalis subsp. lactis BB-12-supplemented yogurt</description>
        </group>
        <group group_id="B3">
          <title>Not Randomized</title>
          <description>Withdrawals prior to randomization</description>
        </group>
        <group group_id="B4">
          <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="20"/>
            <count group_id="B2" value="42"/>
            <count group_id="B3" value="4"/>
            <count group_id="B4" value="66"/>
          </count_list>
        </analyzed>
      </analyzed_list>
      <measure_list>
        <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="29.4" spread="8.1"/>
                    <measurement group_id="B2" value="29.6" spread="10.3"/>
                    <measurement group_id="B3" value="31.8" spread="21.6"/>
                    <measurement group_id="B4" value="29.7" spread="10.6"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
        <measure>
          <title>Sex/Gender, Customized</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="11"/>
                    <measurement group_id="B2" value="23"/>
                    <measurement group_id="B3" value="1"/>
                    <measurement group_id="B4" value="35"/>
                  </measurement_list>
                </category>
                <category>
                  <title>Male</title>
                  <measurement_list>
                    <measurement group_id="B1" value="9"/>
                    <measurement group_id="B2" value="18"/>
                    <measurement group_id="B3" value="3"/>
                    <measurement group_id="B4" value="30"/>
                  </measurement_list>
                </category>
                <category>
                  <title>Not reported</title>
                  <measurement_list>
                    <measurement group_id="B1" value="0"/>
                    <measurement group_id="B2" value="1"/>
                    <measurement group_id="B3" value="0"/>
                    <measurement group_id="B4" value="1"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
        <measure>
          <title>Ethnicity (NIH/OMB)</title>
          <units>Participants</units>
          <param>Count of Participants</param>
          <class_list>
            <class>
              <category_list>
                <category>
                  <title>Hispanic or Latino</title>
                  <measurement_list>
                    <measurement group_id="B1" value="2"/>
                    <measurement group_id="B2" value="2"/>
                    <measurement group_id="B3" value="0"/>
                    <measurement group_id="B4" value="4"/>
                  </measurement_list>
                </category>
                <category>
                  <title>Not Hispanic or Latino</title>
                  <measurement_list>
                    <measurement group_id="B1" value="18"/>
                    <measurement group_id="B2" value="36"/>
                    <measurement group_id="B3" value="4"/>
                    <measurement group_id="B4" value="58"/>
                  </measurement_list>
                </category>
                <category>
                  <title>Unknown or Not Reported</title>
                  <measurement_list>
                    <measurement group_id="B1" value="0"/>
                    <measurement group_id="B2" value="4"/>
                    <measurement group_id="B3" value="0"/>
                    <measurement group_id="B4" value="4"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
        <measure>
          <title>Race (NIH/OMB)</title>
          <units>Participants</units>
          <param>Count of Participants</param>
          <class_list>
            <class>
              <category_list>
                <category>
                  <title>American Indian or Alaska Native</title>
                  <measurement_list>
                    <measurement group_id="B1" value="0"/>
                    <measurement group_id="B2" value="0"/>
                    <measurement group_id="B3" value="0"/>
                    <measurement group_id="B4" value="0"/>
                  </measurement_list>
                </category>
                <category>
                  <title>Asian</title>
                  <measurement_list>
                    <measurement group_id="B1" value="3"/>
                    <measurement group_id="B2" value="6"/>
                    <measurement group_id="B3" value="3"/>
                    <measurement group_id="B4" value="12"/>
                  </measurement_list>
                </category>
                <category>
                  <title>Native Hawaiian or Other Pacific Islander</title>
                  <measurement_list>
                    <measurement group_id="B1" value="0"/>
                    <measurement group_id="B2" value="0"/>
                    <measurement group_id="B3" value="0"/>
                    <measurement group_id="B4" value="0"/>
                  </measurement_list>
                </category>
                <category>
                  <title>Black or African American</title>
                  <measurement_list>
                    <measurement group_id="B1" value="5"/>
                    <measurement group_id="B2" value="8"/>
                    <measurement group_id="B3" value="0"/>
                    <measurement group_id="B4" value="13"/>
                  </measurement_list>
                </category>
                <category>
                  <title>White</title>
                  <measurement_list>
                    <measurement group_id="B1" value="11"/>
                    <measurement group_id="B2" value="28"/>
                    <measurement group_id="B3" value="1"/>
                    <measurement group_id="B4" value="40"/>
                  </measurement_list>
                </category>
                <category>
                  <title>More than one race</title>
                  <measurement_list>
                    <measurement group_id="B1" value="1"/>
                    <measurement group_id="B2" value="0"/>
                    <measurement group_id="B3" value="0"/>
                    <measurement group_id="B4" value="1"/>
                  </measurement_list>
                </category>
                <category>
                  <title>Unknown or Not Reported</title>
                  <measurement_list>
                    <measurement group_id="B1" value="0"/>
                    <measurement group_id="B2" value="0"/>
                    <measurement group_id="B3" value="0"/>
                    <measurement group_id="B4" value="0"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
        <measure>
          <title>Health insurance status</title>
          <units>Participants</units>
          <param>Count of Participants</param>
          <class_list>
            <class>
              <category_list>
                <category>
                  <title>Yes</title>
                  <measurement_list>
                    <measurement group_id="B1" value="20"/>
                    <measurement group_id="B2" value="41"/>
                    <measurement group_id="B3" value="4"/>
                    <measurement group_id="B4" value="65"/>
                  </measurement_list>
                </category>
                <category>
                  <title>No</title>
                  <measurement_list>
                    <measurement group_id="B1" value="0"/>
                    <measurement group_id="B2" value="1"/>
                    <measurement group_id="B3" value="0"/>
                    <measurement group_id="B4" value="1"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
        <measure>
          <title>Household smoking</title>
          <units>Participants</units>
          <param>Count of Participants</param>
          <class_list>
            <class>
              <category_list>
                <category>
                  <title>No</title>
                  <measurement_list>
                    <measurement group_id="B1" value="18"/>
                    <measurement group_id="B2" value="40"/>
                    <measurement group_id="B3" value="4"/>
                    <measurement group_id="B4" value="62"/>
                  </measurement_list>
                </category>
                <category>
                  <title>Yes</title>
                  <measurement_list>
                    <measurement group_id="B1" value="2"/>
                    <measurement group_id="B2" value="2"/>
                    <measurement group_id="B3" value="0"/>
                    <measurement group_id="B4" value="4"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
        <measure>
          <title>Marital status</title>
          <units>Participants</units>
          <param>Count of Participants</param>
          <class_list>
            <class>
              <category_list>
                <category>
                  <title>Married</title>
                  <measurement_list>
                    <measurement group_id="B1" value="4"/>
                    <measurement group_id="B2" value="10"/>
                    <measurement group_id="B3" value="0"/>
                    <measurement group_id="B4" value="14"/>
                  </measurement_list>
                </category>
                <category>
                  <title>Living with a partner</title>
                  <measurement_list>
                    <measurement group_id="B1" value="2"/>
                    <measurement group_id="B2" value="5"/>
                    <measurement group_id="B3" value="0"/>
                    <measurement group_id="B4" value="7"/>
                  </measurement_list>
                </category>
                <category>
                  <title>Single</title>
                  <measurement_list>
                    <measurement group_id="B1" value="14"/>
                    <measurement group_id="B2" value="26"/>
                    <measurement group_id="B3" value="3"/>
                    <measurement group_id="B4" value="43"/>
                  </measurement_list>
                </category>
                <category>
                  <title>Separated</title>
                  <measurement_list>
                    <measurement group_id="B1" value="0"/>
                    <measurement group_id="B2" value="0"/>
                    <measurement group_id="B3" value="0"/>
                    <measurement group_id="B4" value="0"/>
                  </measurement_list>
                </category>
                <category>
                  <title>Divorced</title>
                  <measurement_list>
                    <measurement group_id="B1" value="0"/>
                    <measurement group_id="B2" value="0"/>
                    <measurement group_id="B3" value="0"/>
                    <measurement group_id="B4" value="0"/>
                  </measurement_list>
                </category>
                <category>
                  <title>Widowed</title>
                  <measurement_list>
                    <measurement group_id="B1" value="0"/>
                    <measurement group_id="B2" value="1"/>
                    <measurement group_id="B3" value="1"/>
                    <measurement group_id="B4" value="2"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
        <measure>
          <title>Annual gross total income</title>
          <units>Participants</units>
          <param>Count of Participants</param>
          <class_list>
            <class>
              <category_list>
                <category>
                  <title>Less than $15,000</title>
                  <measurement_list>
                    <measurement group_id="B1" value="1"/>
                    <measurement group_id="B2" value="6"/>
                    <measurement group_id="B3" value="0"/>
                    <measurement group_id="B4" value="7"/>
                  </measurement_list>
                </category>
                <category>
                  <title>$15,000-$29,999</title>
                  <measurement_list>
                    <measurement group_id="B1" value="1"/>
                    <measurement group_id="B2" value="3"/>
                    <measurement group_id="B3" value="0"/>
                    <measurement group_id="B4" value="4"/>
                  </measurement_list>
                </category>
                <category>
                  <title>$30,000-$49,999</title>
                  <measurement_list>
                    <measurement group_id="B1" value="1"/>
                    <measurement group_id="B2" value="5"/>
                    <measurement group_id="B3" value="0"/>
                    <measurement group_id="B4" value="6"/>
                  </measurement_list>
                </category>
                <category>
                  <title>$50,000-$74,999</title>
                  <measurement_list>
                    <measurement group_id="B1" value="1"/>
                    <measurement group_id="B2" value="5"/>
                    <measurement group_id="B3" value="0"/>
                    <measurement group_id="B4" value="6"/>
                  </measurement_list>
                </category>
                <category>
                  <title>$75,000-$99,999</title>
                  <measurement_list>
                    <measurement group_id="B1" value="5"/>
                    <measurement group_id="B2" value="6"/>
                    <measurement group_id="B3" value="0"/>
                    <measurement group_id="B4" value="11"/>
                  </measurement_list>
                </category>
                <category>
                  <title>$100,000-$150,999</title>
                  <measurement_list>
                    <measurement group_id="B1" value="2"/>
                    <measurement group_id="B2" value="2"/>
                    <measurement group_id="B3" value="0"/>
                    <measurement group_id="B4" value="4"/>
                  </measurement_list>
                </category>
                <category>
                  <title>$150,000-$200,000</title>
                  <measurement_list>
                    <measurement group_id="B1" value="1"/>
                    <measurement group_id="B2" value="1"/>
                    <measurement group_id="B3" value="0"/>
                    <measurement group_id="B4" value="2"/>
                  </measurement_list>
                </category>
                <category>
                  <title>More than $200,000</title>
                  <measurement_list>
                    <measurement group_id="B1" value="2"/>
                    <measurement group_id="B2" value="6"/>
                    <measurement group_id="B3" value="3"/>
                    <measurement group_id="B4" value="11"/>
                  </measurement_list>
                </category>
                <category>
                  <title>Prefer not to answer</title>
                  <measurement_list>
                    <measurement group_id="B1" value="0"/>
                    <measurement group_id="B2" value="3"/>
                    <measurement group_id="B3" value="0"/>
                    <measurement group_id="B4" value="3"/>
                  </measurement_list>
                </category>
                <category>
                  <title>Unknown/Not Reported</title>
                  <measurement_list>
                    <measurement group_id="B1" value="6"/>
                    <measurement group_id="B2" value="5"/>
                    <measurement group_id="B3" value="1"/>
                    <measurement group_id="B4" value="12"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </measure_list>
    </baseline>

    <outcome_list>
      <outcome>
        <type>Primary</type>
        <title>Level of Fecal Short-chain Fatty Acid (SCFA) Acetate</title>
        <description>Level of fecal short-chain fatty acid acetate (SCFA) after administration of amoxicillin clavulanate</description>
        <time_frame>day 0 (post run-in), 7, 14, 21, 30</time_frame>
        <population>Number of samples received</population>
        <group_list>
          <group group_id="O1">
            <title>Control</title>
            <description>Yogurt without Bifidobacterium animalis subsp. lactis BB-12 (BB-12) and Amoxicillin-Clavulanate 875 Mg-125 Mg Oral Tablet&#xD;
Amoxicillin-Clavulanate 875 Mg-125 Mg Oral Tablet: Amoxicillin-Clavulanate 875 Mg-125 Mg Oral Tablet&#xD;
Control: Yogurt without Bifidobacterium animalis subsp. lactis BB-12 (BB-12)</description>
          </group>
          <group group_id="O2">
            <title>BB-12</title>
            <description>Bifidobacterium animalis subsp. lactis BB-12 (BB-12)-supplemented yogurt and Amoxicillin-Clavulanate 875 Mg-125 Mg Oral Tablet&#xD;
Amoxicillin-Clavulanate 875 Mg-125 Mg Oral Tablet: Amoxicillin-Clavulanate 875 Mg-125 Mg Oral Tablet&#xD;
BB-12: Bifidobacterium animalis subsp. lactis BB-12-supplemented yogurt</description>
          </group>
        </group_list>
        <measure>
          <title>Level of Fecal Short-chain Fatty Acid (SCFA) Acetate</title>
          <description>Level of fecal short-chain fatty acid acetate (SCFA) after administration of amoxicillin clavulanate</description>
          <population>Number of samples received</population>
          <units>micromolar (μM)</units>
          <param>Mean</param>
          <dispersion>Standard Deviation</dispersion>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="12"/>
                <count group_id="O2" value="29"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <title>Day 0</title>
              <analyzed_list>
                <analyzed>
                  <units>Participants</units>
                  <scope>Class</scope>
                  <count_list>
                    <count group_id="O1" value="12"/>
                    <count group_id="O2" value="29"/>
                  </count_list>
                </analyzed>
              </analyzed_list>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="53.1" spread="18.0"/>
                    <measurement group_id="O2" value="45.2" spread="20.3"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Day 7</title>
              <analyzed_list>
                <analyzed>
                  <units>Participants</units>
                  <scope>Class</scope>
                  <count_list>
                    <count group_id="O1" value="12"/>
                    <count group_id="O2" value="27"/>
                  </count_list>
                </analyzed>
              </analyzed_list>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="42.3" spread="17.5"/>
                    <measurement group_id="O2" value="38.1" spread="17.6"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Day 14</title>
              <analyzed_list>
                <analyzed>
                  <units>Participants</units>
                  <scope>Class</scope>
                  <count_list>
                    <count group_id="O1" value="12"/>
                    <count group_id="O2" value="29"/>
                  </count_list>
                </analyzed>
              </analyzed_list>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="36.8" spread="11.1"/>
                    <measurement group_id="O2" value="40.8" spread="16.1"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Day 21</title>
              <analyzed_list>
                <analyzed>
                  <units>Participants</units>
                  <scope>Class</scope>
                  <count_list>
                    <count group_id="O1" value="12"/>
                    <count group_id="O2" value="29"/>
                  </count_list>
                </analyzed>
              </analyzed_list>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="43.8" spread="17.6"/>
                    <measurement group_id="O2" value="50.5" spread="20.9"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Day 30</title>
              <analyzed_list>
                <analyzed>
                  <units>Participants</units>
                  <scope>Class</scope>
                  <count_list>
                    <count group_id="O1" value="10"/>
                    <count group_id="O2" value="26"/>
                  </count_list>
                </analyzed>
              </analyzed_list>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="39.8" spread="14.3"/>
                    <measurement group_id="O2" value="44.5" spread="14.1"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </outcome>
      <outcome>
        <type>Secondary</type>
        <title>Level of Fecal SCFA Propionate</title>
        <description>Level of fecal short-chain fatty acid propionate after administration of amoxicillin clavulanate</description>
        <time_frame>day 0 (post run-in), 7, 14, 21, 30</time_frame>
        <population>Number of samples received</population>
        <group_list>
          <group group_id="O1">
            <title>Control</title>
            <description>Yogurt without Bifidobacterium animalis subsp. lactis BB-12 (BB-12) and Amoxicillin-Clavulanate 875 Mg-125 Mg Oral Tablet&#xD;
Amoxicillin-Clavulanate 875 Mg-125 Mg Oral Tablet: Amoxicillin-Clavulanate 875 Mg-125 Mg Oral Tablet&#xD;
Control: Yogurt without Bifidobacterium animalis subsp. lactis BB-12 (BB-12)</description>
          </group>
          <group group_id="O2">
            <title>BB-12</title>
            <description>Bifidobacterium animalis subsp. lactis BB-12 (BB-12)-supplemented yogurt and Amoxicillin-Clavulanate 875 Mg-125 Mg Oral Tablet&#xD;
Amoxicillin-Clavulanate 875 Mg-125 Mg Oral Tablet: Amoxicillin-Clavulanate 875 Mg-125 Mg Oral Tablet&#xD;
BB-12: Bifidobacterium animalis subsp. lactis BB-12-supplemented yogurt</description>
          </group>
        </group_list>
        <measure>
          <title>Level of Fecal SCFA Propionate</title>
          <description>Level of fecal short-chain fatty acid propionate after administration of amoxicillin clavulanate</description>
          <population>Number of samples received</population>
          <units>μM</units>
          <param>Mean</param>
          <dispersion>Standard Deviation</dispersion>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="12"/>
                <count group_id="O2" value="29"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <title>Day 0</title>
              <analyzed_list>
                <analyzed>
                  <units>Participants</units>
                  <scope>Class</scope>
                  <count_list>
                    <count group_id="O1" value="12"/>
                    <count group_id="O2" value="29"/>
                  </count_list>
                </analyzed>
              </analyzed_list>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="14.3" spread="9.1"/>
                    <measurement group_id="O2" value="13.0" spread="7.2"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Day 7</title>
              <analyzed_list>
                <analyzed>
                  <units>Participants</units>
                  <scope>Class</scope>
                  <count_list>
                    <count group_id="O1" value="12"/>
                    <count group_id="O2" value="25"/>
                  </count_list>
                </analyzed>
              </analyzed_list>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="14.3" spread="6.7"/>
                    <measurement group_id="O2" value="12.5" spread="6.0"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Day 14</title>
              <analyzed_list>
                <analyzed>
                  <units>Participants</units>
                  <scope>Class</scope>
                  <count_list>
                    <count group_id="O1" value="12"/>
                    <count group_id="O2" value="29"/>
                  </count_list>
                </analyzed>
              </analyzed_list>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="11.8" spread="6.9"/>
                    <measurement group_id="O2" value="12.0" spread="6.1"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Day 21</title>
              <analyzed_list>
                <analyzed>
                  <units>Participants</units>
                  <scope>Class</scope>
                  <count_list>
                    <count group_id="O1" value="11"/>
                    <count group_id="O2" value="29"/>
                  </count_list>
                </analyzed>
              </analyzed_list>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="11.0" spread="3.5"/>
                    <measurement group_id="O2" value="14.8" spread="7.8"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Day 30</title>
              <analyzed_list>
                <analyzed>
                  <units>Participants</units>
                  <scope>Class</scope>
                  <count_list>
                    <count group_id="O1" value="11"/>
                    <count group_id="O2" value="26"/>
                  </count_list>
                </analyzed>
              </analyzed_list>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="11.4" spread="7.3"/>
                    <measurement group_id="O2" value="11.5" spread="5.7"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </outcome>
      <outcome>
        <type>Secondary</type>
        <title>Level of Fecal SCFA Butyrate</title>
        <description>Level of fecal short-chain fatty acid butyrate (μM) after administration of amoxicillin clavulanate</description>
        <time_frame>day 0 (post run-in), 7, 14, 21, 30</time_frame>
        <population>Number of samples received</population>
        <group_list>
          <group group_id="O1">
            <title>Control</title>
            <description>Yogurt without Bifidobacterium animalis subsp. lactis BB-12 (BB-12) and Amoxicillin-Clavulanate 875 Mg-125 Mg Oral Tablet&#xD;
Amoxicillin-Clavulanate 875 Mg-125 Mg Oral Tablet: Amoxicillin-Clavulanate 875 Mg-125 Mg Oral Tablet&#xD;
Control: Yogurt without Bifidobacterium animalis subsp. lactis BB-12 (BB-12)</description>
          </group>
          <group group_id="O2">
            <title>BB-12</title>
            <description>Bifidobacterium animalis subsp. lactis BB-12 (BB-12)-supplemented yogurt and Amoxicillin-Clavulanate 875 Mg-125 Mg Oral Tablet&#xD;
Amoxicillin-Clavulanate 875 Mg-125 Mg Oral Tablet: Amoxicillin-Clavulanate 875 Mg-125 Mg Oral Tablet&#xD;
BB-12: Bifidobacterium animalis subsp. lactis BB-12-supplemented yogurt</description>
          </group>
        </group_list>
        <measure>
          <title>Level of Fecal SCFA Butyrate</title>
          <description>Level of fecal short-chain fatty acid butyrate (μM) after administration of amoxicillin clavulanate</description>
          <population>Number of samples received</population>
          <units>μM</units>
          <param>Mean</param>
          <dispersion>Standard Deviation</dispersion>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="12"/>
                <count group_id="O2" value="29"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <title>Day 0</title>
              <analyzed_list>
                <analyzed>
                  <units>Participants</units>
                  <scope>Class</scope>
                  <count_list>
                    <count group_id="O1" value="11"/>
                    <count group_id="O2" value="29"/>
                  </count_list>
                </analyzed>
              </analyzed_list>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="12.7" spread="6.2"/>
                    <measurement group_id="O2" value="12.7" spread="8.4"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Day 7</title>
              <analyzed_list>
                <analyzed>
                  <units>Participants</units>
                  <scope>Class</scope>
                  <count_list>
                    <count group_id="O1" value="11"/>
                    <count group_id="O2" value="24"/>
                  </count_list>
                </analyzed>
              </analyzed_list>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="9.0" spread="5.3"/>
                    <measurement group_id="O2" value="8.3" spread="5.7"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Day 14</title>
              <analyzed_list>
                <analyzed>
                  <units>Participants</units>
                  <scope>Class</scope>
                  <count_list>
                    <count group_id="O1" value="12"/>
                    <count group_id="O2" value="29"/>
                  </count_list>
                </analyzed>
              </analyzed_list>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="7.4" spread="4.3"/>
                    <measurement group_id="O2" value="8.9" spread="6.1"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Day 21</title>
              <analyzed_list>
                <analyzed>
                  <units>Participants</units>
                  <scope>Class</scope>
                  <count_list>
                    <count group_id="O1" value="11"/>
                    <count group_id="O2" value="29"/>
                  </count_list>
                </analyzed>
              </analyzed_list>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="11.6" spread="9.2"/>
                    <measurement group_id="O2" value="11.9" spread="7.8"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Day 30</title>
              <analyzed_list>
                <analyzed>
                  <units>Participants</units>
                  <scope>Class</scope>
                  <count_list>
                    <count group_id="O1" value="11"/>
                    <count group_id="O2" value="26"/>
                  </count_list>
                </analyzed>
              </analyzed_list>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="8.3" spread="5.3"/>
                    <measurement group_id="O2" value="9.9" spread="4.0"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </outcome>
      <outcome>
        <type>Other Pre-specified</type>
        <title>Change in Community Diversity (Shannon Diversity Index) From Pre run-in Baseline</title>
        <description>The Shannon diversity metric is a measure of community diversity and takes into account species richness (number of distinct taxa) and the relative abundance of each taxon. The Shannon diversity index was calculated for samples at each time point from subjects receiving control or BB-12 yogurt. The first of two baseline samples was collected from each subject at the time of enrollment (pre run-in) before a 30-day run-in period in which the consumption of dietary probiotics was stopped. A higher index indicates more diversity and a lower index indicates less diversity.</description>
        <time_frame>day 0 (pre run-in), 7, 14, 21, 30</time_frame>
        <population>Number of samples received</population>
        <group_list>
          <group group_id="O1">
            <title>Control</title>
            <description>Yogurt without Bifidobacterium animalis subsp. lactis BB-12 (BB-12) and Amoxicillin-Clavulanate 875 Mg-125 Mg Oral Tablet&#xD;
Amoxicillin-Clavulanate 875 Mg-125 Mg Oral Tablet: Amoxicillin-Clavulanate 875 Mg-125 Mg Oral Tablet&#xD;
Control: Yogurt without Bifidobacterium animalis subsp. lactis BB-12 (BB-12)</description>
          </group>
          <group group_id="O2">
            <title>BB-12</title>
            <description>Bifidobacterium animalis subsp. lactis BB-12 (BB-12)-supplemented yogurt and Amoxicillin-Clavulanate 875 Mg-125 Mg Oral Tablet&#xD;
Amoxicillin-Clavulanate 875 Mg-125 Mg Oral Tablet: Amoxicillin-Clavulanate 875 Mg-125 Mg Oral Tablet&#xD;
BB-12: Bifidobacterium animalis subsp. lactis BB-12-supplemented yogurt</description>
          </group>
        </group_list>
        <measure>
          <title>Change in Community Diversity (Shannon Diversity Index) From Pre run-in Baseline</title>
          <description>The Shannon diversity metric is a measure of community diversity and takes into account species richness (number of distinct taxa) and the relative abundance of each taxon. The Shannon diversity index was calculated for samples at each time point from subjects receiving control or BB-12 yogurt. The first of two baseline samples was collected from each subject at the time of enrollment (pre run-in) before a 30-day run-in period in which the consumption of dietary probiotics was stopped. A higher index indicates more diversity and a lower index indicates less diversity.</description>
          <population>Number of samples received</population>
          <units>Shannon Diversity Index</units>
          <param>Mean</param>
          <dispersion>Standard Deviation</dispersion>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="18"/>
                <count group_id="O2" value="38"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <title>Day 0 Pre run-in</title>
              <analyzed_list>
                <analyzed>
                  <units>Participants</units>
                  <scope>Class</scope>
                  <count_list>
                    <count group_id="O1" value="15"/>
                    <count group_id="O2" value="31"/>
                  </count_list>
                </analyzed>
              </analyzed_list>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="3.711" spread="0.349"/>
                    <measurement group_id="O2" value="3.774" spread="0.302"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Day 7</title>
              <analyzed_list>
                <analyzed>
                  <units>Participants</units>
                  <scope>Class</scope>
                  <count_list>
                    <count group_id="O1" value="10"/>
                    <count group_id="O2" value="28"/>
                  </count_list>
                </analyzed>
              </analyzed_list>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="3.380" spread="0.364"/>
                    <measurement group_id="O2" value="3.567" spread="0.479"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Day 14</title>
              <analyzed_list>
                <analyzed>
                  <units>Participants</units>
                  <scope>Class</scope>
                  <count_list>
                    <count group_id="O1" value="13"/>
                    <count group_id="O2" value="32"/>
                  </count_list>
                </analyzed>
              </analyzed_list>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="3.419" spread="0.465"/>
                    <measurement group_id="O2" value="3.632" spread="0.307"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Day 21</title>
              <analyzed_list>
                <analyzed>
                  <units>Participants</units>
                  <scope>Class</scope>
                  <count_list>
                    <count group_id="O1" value="10"/>
                    <count group_id="O2" value="27"/>
                  </count_list>
                </analyzed>
              </analyzed_list>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="3.709" spread="0.322"/>
                    <measurement group_id="O2" value="3.708" spread="0.308"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Day 30</title>
              <analyzed_list>
                <analyzed>
                  <units>Participants</units>
                  <scope>Class</scope>
                  <count_list>
                    <count group_id="O1" value="11"/>
                    <count group_id="O2" value="27"/>
                  </count_list>
                </analyzed>
              </analyzed_list>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="3.395" spread="0.409"/>
                    <measurement group_id="O2" value="3.684" spread="0.397"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </outcome>
      <outcome>
        <type>Other Pre-specified</type>
        <title>Change in Community Diversity (Shannon Diversity Index) From Post run-in Baseline</title>
        <description>The Shannon diversity metric is a measure of community diversity and takes into account species richness (number of distinct taxa) and the relative abundance of each taxon. The Shannon diversity index was calculated for samples at each time point from subjects receiving control or BB-12 yogurt. The second baseline sample was collected from each subject after a 30-day run-in period in which the consumption of dietary probiotics was stopped (post run-in). A higher index indicates more diversity and a lower index indicates less diversity.</description>
        <time_frame>day 0 (post run-in), 7, 14, 21, 30</time_frame>
        <population>Number of samples received</population>
        <group_list>
          <group group_id="O1">
            <title>Control</title>
            <description>Yogurt without Bifidobacterium animalis subsp. lactis BB-12 (BB-12) and Amoxicillin-Clavulanate 875 Mg-125 Mg Oral Tablet&#xD;
Amoxicillin-Clavulanate 875 Mg-125 Mg Oral Tablet: Amoxicillin-Clavulanate 875 Mg-125 Mg Oral Tablet&#xD;
Control: Yogurt without Bifidobacterium animalis subsp. lactis BB-12 (BB-12)</description>
          </group>
          <group group_id="O2">
            <title>BB-12</title>
            <description>Bifidobacterium animalis subsp. lactis BB-12 (BB-12)-supplemented yogurt and Amoxicillin-Clavulanate 875 Mg-125 Mg Oral Tablet&#xD;
Amoxicillin-Clavulanate 875 Mg-125 Mg Oral Tablet: Amoxicillin-Clavulanate 875 Mg-125 Mg Oral Tablet&#xD;
BB-12: Bifidobacterium animalis subsp. lactis BB-12-supplemented yogurt</description>
          </group>
        </group_list>
        <measure>
          <title>Change in Community Diversity (Shannon Diversity Index) From Post run-in Baseline</title>
          <description>The Shannon diversity metric is a measure of community diversity and takes into account species richness (number of distinct taxa) and the relative abundance of each taxon. The Shannon diversity index was calculated for samples at each time point from subjects receiving control or BB-12 yogurt. The second baseline sample was collected from each subject after a 30-day run-in period in which the consumption of dietary probiotics was stopped (post run-in). A higher index indicates more diversity and a lower index indicates less diversity.</description>
          <population>Number of samples received</population>
          <units>Shannon Diversity Index</units>
          <param>Mean</param>
          <dispersion>Standard Deviation</dispersion>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="18"/>
                <count group_id="O2" value="38"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <title>Day 0 Post run-in</title>
              <analyzed_list>
                <analyzed>
                  <units>Participants</units>
                  <scope>Class</scope>
                  <count_list>
                    <count group_id="O1" value="15"/>
                    <count group_id="O2" value="29"/>
                  </count_list>
                </analyzed>
              </analyzed_list>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="3.845" spread="0.290"/>
                    <measurement group_id="O2" value="3.718" spread="0.261"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Day 7</title>
              <analyzed_list>
                <analyzed>
                  <units>Participants</units>
                  <scope>Class</scope>
                  <count_list>
                    <count group_id="O1" value="11"/>
                    <count group_id="O2" value="25"/>
                  </count_list>
                </analyzed>
              </analyzed_list>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="3.528" spread="0.396"/>
                    <measurement group_id="O2" value="3.606" spread="0.494"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Day 14</title>
              <analyzed_list>
                <analyzed>
                  <units>Participants</units>
                  <scope>Class</scope>
                  <count_list>
                    <count group_id="O1" value="13"/>
                    <count group_id="O2" value="26"/>
                  </count_list>
                </analyzed>
              </analyzed_list>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="3.496" spread="0.486"/>
                    <measurement group_id="O2" value="3.666" spread="0.304"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Day 21</title>
              <analyzed_list>
                <analyzed>
                  <units>Participants</units>
                  <scope>Class</scope>
                  <count_list>
                    <count group_id="O1" value="10"/>
                    <count group_id="O2" value="23"/>
                  </count_list>
                </analyzed>
              </analyzed_list>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="3.785" spread="0.295"/>
                    <measurement group_id="O2" value="3.727" spread="0.278"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Day 30</title>
              <analyzed_list>
                <analyzed>
                  <units>Participants</units>
                  <scope>Class</scope>
                  <count_list>
                    <count group_id="O1" value="11"/>
                    <count group_id="O2" value="23"/>
                  </count_list>
                </analyzed>
              </analyzed_list>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="3.486" spread="0.444"/>
                    <measurement group_id="O2" value="3.712" spread="0.391"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </outcome>
      <outcome>
        <type>Other Pre-specified</type>
        <title>Bray-Curtis Dissimilarity</title>
        <description>Community divergence over time with respect to the baseline sample (post run-in, day 0)</description>
        <time_frame>day 0, 7, 14, 21, 30</time_frame>
      </outcome>
      <outcome>
        <type>Other Pre-specified</type>
        <title>Change in Diarrhea/Stool Frequency</title>
        <description>Change in diarrhea/stool frequency from baseline</description>
        <time_frame>day 7, 14, 21, 30</time_frame>
      </outcome>
    </outcome_list>

    <reported_events>
      <time_frame>Pre-run in baseline to day 30</time_frame>
      <group_list>
        <group group_id="E1">
          <title>Control</title>
          <description>Yogurt without Bifidobacterium animalis subsp. lactis BB-12 (BB-12) and Amoxicillin-Clavulanate 875 Mg-125 Mg Oral Tablet&#xD;
Amoxicillin-Clavulanate 875 Mg-125 Mg Oral Tablet: Amoxicillin-Clavulanate 875 Mg-125 Mg Oral Tablet&#xD;
Control: Yogurt without Bifidobacterium animalis subsp. lactis BB-12 (BB-12)</description>
        </group>
        <group group_id="E2">
          <title>BB-12</title>
          <description>Bifidobacterium animalis subsp. lactis BB-12 (BB-12)-supplemented yogurt and Amoxicillin-Clavulanate 875 Mg-125 Mg Oral Tablet&#xD;
Amoxicillin-Clavulanate 875 Mg-125 Mg Oral Tablet: Amoxicillin-Clavulanate 875 Mg-125 Mg Oral Tablet&#xD;
BB-12: Bifidobacterium animalis subsp. lactis BB-12-supplemented yogurt</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="0" subjects_at_risk="20"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="42"/>
              </event>
              <event>
                <sub_title>Total, serious adverse events</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="20"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="42"/>
              </event>
            </event_list>
          </category>
        </category_list>
      </serious_events>
      <other_events>
        <frequency_threshold>0</frequency_threshold>
        <default_assessment>Non-systematic Assessment</default_assessment>
        <category_list>
          <category>
            <title>Total</title>
            <event_list>
              <event>
                <sub_title>Total, other adverse events</sub_title>
                <counts group_id="E1" subjects_affected="15" subjects_at_risk="18"/>
                <counts group_id="E2" subjects_affected="25" subjects_at_risk="38"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Gastrointestinal disorders</title>
            <event_list>
              <event>
                <sub_title>Loose stool</sub_title>
                <counts group_id="E1" subjects_affected="9" subjects_at_risk="18"/>
                <counts group_id="E2" subjects_affected="14" subjects_at_risk="38"/>
              </event>
              <event>
                <sub_title>Diarrhea</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="18"/>
                <counts group_id="E2" subjects_affected="1" subjects_at_risk="38"/>
              </event>
              <event>
                <sub_title>Constipation</sub_title>
                <counts group_id="E1" subjects_affected="3" subjects_at_risk="18"/>
                <counts group_id="E2" subjects_affected="4" subjects_at_risk="38"/>
              </event>
              <event>
                <sub_title>Flatulence</sub_title>
                <counts group_id="E1" subjects_affected="8" subjects_at_risk="18"/>
                <counts group_id="E2" subjects_affected="8" subjects_at_risk="38"/>
              </event>
              <event>
                <sub_title>Stomach Pain</sub_title>
                <counts group_id="E1" subjects_affected="3" subjects_at_risk="18"/>
                <counts group_id="E2" subjects_affected="1" subjects_at_risk="38"/>
              </event>
              <event>
                <sub_title>Vomiting</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="18"/>
                <counts group_id="E2" subjects_affected="2" subjects_at_risk="38"/>
              </event>
              <event>
                <sub_title>Dyspepsia</sub_title>
                <counts group_id="E1" subjects_affected="3" subjects_at_risk="18"/>
                <counts group_id="E2" subjects_affected="1" subjects_at_risk="38"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>General disorders</title>
            <event_list>
              <event>
                <sub_title>Lack/Loss of Appetite</sub_title>
                <counts group_id="E1" subjects_affected="3" subjects_at_risk="18"/>
                <counts group_id="E2" subjects_affected="2" subjects_at_risk="38"/>
              </event>
              <event>
                <sub_title>Rash</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="18"/>
                <counts group_id="E2" subjects_affected="2" subjects_at_risk="38"/>
              </event>
              <event>
                <sub_title>Nausea</sub_title>
                <counts group_id="E1" subjects_affected="5" subjects_at_risk="18"/>
                <counts group_id="E2" subjects_affected="3" subjects_at_risk="38"/>
              </event>
              <event>
                <sub_title>Other</sub_title>
                <counts group_id="E1" subjects_affected="6" subjects_at_risk="18"/>
                <counts group_id="E2" subjects_affected="7" subjects_at_risk="38"/>
              </event>
            </event_list>
          </category>
        </category_list>
      </other_events>
    </reported_events>

    <certain_agreements>
      <pi_employee>Principal Investigators are NOT 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>
    <point_of_contact>
      <name_or_title>Daniel Merenstein, MD</name_or_title>
      <organization>Department of Family Medicine, Georgetown University Medical Center</organization>
      <phone>202-687-2745</phone>
      <email>djm23@georgetown.edu</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/NCT03755765
org study id: 2018-0736
secondary id: 1R61AT009622-01A1
nct id: NCT03755765
lead sponsor: 
collaborator: 
collaborator: 
has dmc: Yes
is fda regulated drug: Yes
is fda regulated device: No
The focus of the study is to better understand the mechanisms causing antibiotic-associated
      diarrhea (AAD) and how probiotics may prevent some of the iatrogenic effects of antibiotic
      medications. One of the most common indications for probiotics is for prevention of
      antibiotic-associated diarrhea. Clinically, different probiotic strains have demonstrated the
      ability to prevent AAD; however, the mechanism of action behind this effect has not been
      elucidated. Data from several studies suggest that antibiotic-induced disruption of commensal
      bacteria in the colon results in a significant (up to 50%) reduction in short chain fatty
      acid (SCFA) production and a concomitant reduction in Na-dependent fluid absorption resulting
      in AAD. Probiotics have been shown to ameliorate a variety of gastrointestinal disease states
      and thus, the study investigators hypothesize that administration of a probiotic yogurt will
      protect against the development of AAD.
Probiotics are live microorganisms that, when administered in adequate amounts, confer a
      health benefit on the host. One of the most common indications for probiotic treatment is the
      prevention of antibiotic-associated diarrhea (AAD). Unfortunately, the efficacy of many
      probiotic products used for AAD is not supported by rigorous independent research, and
      non-evidence-based clinical usage is common. Data from several studies are consistent with
      the notion that antibiotic-induced disruption of commensal bacteria in the colon results in a
      significant reduction of short chain fatty acid (SCFA) production and a concomitant reduction
      in Na-dependent fluid absorption resulting in AAD. The probiotic strain being studied,
      Bifidobacterium animalis subsp. lactis BB-12 (BB-12), has been shown to ameliorate a variety
      of gastrointestinal disease states and is known to produce acetate at concentrations up to 50
      mM in vitro. Thus, the investigators hypothesize that administration of BB-12 at the same
      time as antibiotic consumption will protect against the development of AAD through its
      ability to generate acetate directly, and also increase other SCFAs through cross-feeding of
      certain bacteria in the Firmicutes phylum such Clostridium, Eubacterium and Roseburia, which
      use acetate to produce butyrate.

      The primary aim of the R61 phase (N=60) is to determine the ability of BB-12 to impact
      antibiotic-induced reduction in SCFA as reflected by the levels of acetate, the most abundant
      primary colonic SCFA. The primary hypothesis is that antibiotics will result in a reduction
      in fecal SCFA, but BB-12 supplementation will protect against antibiotic-induced SCFA
      reduction and/or be associated with a more rapid return to baseline SCFA levels as compared
      to controls. Antibiotics also result in a decrease in total microbial counts and diversity in
      the gut microbiota, disrupting the homeostasis of the gut ecosystem and allowing colonization
      by pathogens. The secondary aim will be to determine the ability of BB-12 to impact
      antibiotic-induced disruption of the gut microbiota with 16S (16 Svedberg) ribosomal
      ribonucleic acid (rRNA) profiling. The secondary hypothesis is that antibiotics will result
      in a decrease in the overall number and diversity of bacterial species present in the fecal
      microbiota, and further BB-12 supplementation will protect against antibiotic-induced shifts
      in the microbiota and/or will be associated with a more rapid return to a baseline microbiota
      composition as compared to controls. The long-term goal is to determine the impact of BB-12
      on a variety of gastrointestinal disease states and ages, through high-level independent
      research. This mechanism elucidation is important for directing future translational and
      effectiveness research.
allocation: Randomized
intervention model: Parallel Assignment
primary purpose: Other
masking: Triple (Participant, Investigator, Outcomes Assessor)
measure: Level of Fecal Short-chain Fatty Acid (SCFA) Acetate
time frame: day 0 (post run-in), 7, 14, 21, 30
description: Level of fecal short-chain fatty acid acetate (SCFA) after administration of amoxicillin clavulanate
measure: Level of Fecal SCFA Propionate
time frame: day 0 (post run-in), 7, 14, 21, 30
description: Level of fecal short-chain fatty acid propionate after administration of amoxicillin clavulanate
measure: Level of Fecal SCFA Butyrate
time frame: day 0 (post run-in), 7, 14, 21, 30
description: Level of fecal short-chain fatty acid butyrate (μM) after administration of amoxicillin clavulanate
measure: Change in Community Diversity (Shannon Diversity Index) From Pre run-in Baseline
time frame: day 0 (pre run-in), 7, 14, 21, 30
description: The Shannon diversity metric is a measure of community diversity and takes into account species richness (number of distinct taxa) and the relative abundance of each taxon. The Shannon diversity index was calculated for samples at each time point from subjects receiving control or BB-12 yogurt. The first of two baseline samples was collected from each subject at the time of enrollment (pre run-in) before a 30-day run-in period in which the consumption of dietary probiotics was stopped. A higher index indicates more diversity and a lower index indicates less diversity.
measure: Change in Community Diversity (Shannon Diversity Index) From Post run-in Baseline
time frame: day 0 (post run-in), 7, 14, 21, 30
description: The Shannon diversity metric is a measure of community diversity and takes into account species richness (number of distinct taxa) and the relative abundance of each taxon. The Shannon diversity index was calculated for samples at each time point from subjects receiving control or BB-12 yogurt. The second baseline sample was collected from each subject after a 30-day run-in period in which the consumption of dietary probiotics was stopped (post run-in). A higher index indicates more diversity and a lower index indicates less diversity.
measure: Bray-Curtis Dissimilarity
time frame: day 0, 7, 14, 21, 30
description: Community divergence over time with respect to the baseline sample (post run-in, day 0)
measure: Change in Diarrhea/Stool Frequency
time frame: day 7, 14, 21, 30
description: Change in diarrhea/stool frequency from baseline
arm group label: Control
arm group type: Placebo Comparator
description: Yogurt without Bifidobacterium animalis subsp. lactis BB-12 (BB-12) and Amoxicillin-Clavulanate 875 Mg-125 Mg Oral Tablet
arm group label: BB-12
arm group type: Experimental
description: Bifidobacterium animalis subsp. lactis BB-12 (BB-12)-supplemented yogurt and Amoxicillin-Clavulanate 875 Mg-125 Mg Oral Tablet
intervention type: Drug
intervention name: Amoxicillin-Clavulanate 875 Mg-125 Mg Oral Tablet
description: Amoxicillin-Clavulanate 875 Mg-125 Mg Oral Tablet
arm group label: BB-12
arm group label: Control
other name: Augmentin
intervention type: Biological
intervention name: BB-12
description: Bifidobacterium animalis subsp. lactis BB-12-supplemented yogurt
arm group label: BB-12
intervention type: Other
intervention name: Control
description: Yogurt without Bifidobacterium animalis subsp. lactis BB-12 (BB-12)
arm group label: Control
criteria: 
gender: All
minimum age: 18 Years
maximum age: 65 Years
healthy volunteers: Accepts Healthy Volunteers
last name: Daniel Merenstein, MD
role: Principal Investigator
affiliation: Georgetown University
last name: Claire Fraser, PhD
role: Principal Investigator
affiliation: University of Maryland, Baltimore
facility: 
country: United States
citation: Merenstein D, Fraser CM, Roberts RF, Liu T, Grant-Beurmann S, Tan TP, Smith KH, Cronin T, Martin OA, Sanders ME, Lucan SC, Kane MA. Bifidobacterium animalis subsp. lactis BB-12 Protects against Antibiotic-Induced Functional and Compositional Changes in Human Fecal Microbiome. Nutrients. 2021 Aug 17;13(8):2814. doi: 10.3390/nu13082814.
PMID: 34444974
responsible party type: Principal Investigator
investigator affiliation: Georgetown University
investigator full name: Daniel Merenstein
investigator title: Director of Research Programs
mesh term: Diarrhea
mesh term: Amoxicillin
mesh term: Clavulanic Acid
mesh term: Clavulanic Acids
mesh term: Amoxicillin-Potassium Clavulanate Combination
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