<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/NCT02252588</url>
  </required_header>
  <id_info>
    <org_study_id>4526</org_study_id>
    <nct_id>NCT02252588</nct_id>
  </id_info>
  <brief_title>The Effect of Chlorhexidine on the Oral and Lung Microbiota in Chronic Obstructive Pulmonary Disease</brief_title>
  <acronym>CLIMB</acronym>
  <official_title>The Effect of Chlorhexidine on the Oral and Lung Microbiota in Chronic Obstructive</official_title>
  <sponsors>
    <lead_sponsor>
      <agency>University of Minnesota</agency>
      <agency_class>Other</agency_class>
    </lead_sponsor>
    <collaborator>
      <agency>Veterans Medical Research Foundation</agency>
      <agency_class>Other</agency_class>
    </collaborator>
    <collaborator>
      <agency>Flight Attendant Medical Research Institute</agency>
      <agency_class>Other</agency_class>
    </collaborator>
  </sponsors>
  <source>University of Minnesota</source>
  <oversight_info>
    <has_dmc>No</has_dmc>
  </oversight_info>
  <brief_summary>
    <textblock>
      Determine the effect of twice-daily chlorhexidine oral rinse on oral and lung microbiota&#xD;
      biomass in subjects with chronic obstructive pulmonary disease (COPD) with chronic&#xD;
      bronchitis. Our primary outcome will be to compare the microbiota biomass (number of bacteria&#xD;
      as measured by 16S rRNA copy number) of induced sputum and the oral cavity before and after 8&#xD;
      weeks of twice-daily chlorhexidine oral rinse (n=25) compared to controls (n=25) using qPCR&#xD;
      and next-generation sequencing of the bacterial 16S rRNA gene comparing total bacterial&#xD;
      biomass&#xD;
    </textblock>
  </brief_summary>
  <detailed_description>
    <textblock>
      Our hypothesis is that 8 weeks of chlorhexidine oral rinse will decrease microbiota biomass&#xD;
      compared to baseline and those on placebo. Furthermore, we hypothesize that chlorhexidine&#xD;
      treatment will: i) decrease lung and oral microbiota diversity; ii) alter microbiota&#xD;
      taxonomic composition in the lung and oral cavity; iii) decrease systemic inflammation as&#xD;
      measured by blood high sensitivity C-reactive protein (hsCRP), fibrinogen and leukocyte&#xD;
      count; and iv) demonstrate a trend towards improvement in respiratory health status as&#xD;
      measured by the Breathlessness, Cough, and Sputum Scale (BCSS)[1, 2] and St. George's&#xD;
      Respiratory Questionnaire (SGRQ).&#xD;
&#xD;
      Subaim 1: Determine if chlorhexidine alters the lung and oral rinse microbiota diversity and&#xD;
      taxonomic composition. Our hypothesis is that chlorhexidine oral rinse will decrease the&#xD;
      diversity (Shannon and inverse Simpson diversity indices) and taxonomic composition of both&#xD;
      oral and lung microbiota compared to those on placebo as determined by next-generation&#xD;
      sequencing of the bacterial 16S rRNA gene.&#xD;
&#xD;
      Subaim 2: Determine the impact of chlorhexidine on systemic inflammation. Our hypothesis is&#xD;
      that the decrease in lung microbiota biomass is associated with a decrease in systemic&#xD;
      inflammation as measured by blood hsCRP, fibrinogen, and leukocyte count.&#xD;
&#xD;
      Subaim 3: Determine if respiratory symptoms associate with the lung microbiota biomass. Our&#xD;
      hypothesis is that chlorhexidine will demonstrate improved respiratory health status as&#xD;
      measured by the BCSS and SGRQ.&#xD;
    </textblock>
  </detailed_description>
  <overall_status>Completed</overall_status>
  <start_date type="Actual">September 1, 2014</start_date>
  <completion_date type="Actual">January 1, 2020</completion_date>
  <primary_completion_date type="Actual">December 15, 2019</primary_completion_date>
  <phase>Phase 2</phase>
  <study_type>Interventional</study_type>
  <has_expanded_access>No</has_expanded_access>
  <study_design_info>
    <allocation>Randomized</allocation>
    <intervention_model>Parallel Assignment</intervention_model>
    <primary_purpose>Basic Science</primary_purpose>
    <masking>Double (Participant, Investigator)</masking>
  </study_design_info>
  <primary_outcome>
    <measure>Change in Sputum Bacteria Biomass</measure>
    <time_frame>Baseline, 8 weeks</time_frame>
    <description>Samples underwent DNA extraction and 16S rRNA quantification and 16S rRNA V4 MiSeq sequencing was performed at the University of Minnesota Genomics Center. The biomass was the number of bacteria as measured by 16S rRNA copy number. To adjust biomass for the size of the sputum sample, raw counts were normalized by dividing by the sample volume or mass.</description>
  </primary_outcome>
  <secondary_outcome>
    <measure>Breathlessness, Cough, and Sputum Scale (BCSS)</measure>
    <time_frame>Baseline, 8 weeks</time_frame>
    <description>The Breathlessness, Cough, and Sputum Scale (BCSS) is a brief, three-item, patient-reported outcome measure in which each of the three symptoms assessed by the measure is represented by a single item. Patients are asked to evaluate each symptom/item on a 5-point Likert-type scale, ranging from 0 to 4. Total scores range from 0 to 12 with higher scores indicating a more severe manifestation of the symptom.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Change in St George Respiratory Quotient (SGRQ)</measure>
    <time_frame>baseline, 8 weeks</time_frame>
    <description>The St George Respiratory Quotient (SGRQ) contains 50 items measuring symptoms of and activities affected by obstructive airway disease. Total score is a sum of item scores and ranges from 0 to 100, with higher scores indicating more limitations. The minimally significant difference is 4.</description>
  </secondary_outcome>
  <number_of_arms>2</number_of_arms>
  <enrollment type="Actual">44</enrollment>
  <condition>Chronic Obstructive Pulmonary Disease</condition>
  <arm_group>
    <arm_group_label>Chlorhexidine</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>Oral Rinse</description>
  </arm_group>
  <arm_group>
    <arm_group_label>Placebo</arm_group_label>
    <arm_group_type>Placebo Comparator</arm_group_type>
    <description>Oral Rinse</description>
  </arm_group>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>Chlorhexidine</intervention_name>
    <description>Oral Rinse</description>
    <arm_group_label>Chlorhexidine</arm_group_label>
    <arm_group_label>Placebo</arm_group_label>
  </intervention>
  <intervention>
    <intervention_type>Other</intervention_type>
    <intervention_name>Placebo</intervention_name>
    <description>Oral Rinse</description>
    <arm_group_label>Chlorhexidine</arm_group_label>
    <arm_group_label>Placebo</arm_group_label>
  </intervention>
  <eligibility>
    <criteria>
      <textblock>
        Inclusion Criteria:&#xD;
&#xD;
          -  Willingness to undergo sputum induction&#xD;
&#xD;
          -  Capability to provide written informed consent&#xD;
&#xD;
          -  Age ≥ 40 years and ≤ 85 years&#xD;
&#xD;
          -  FEV1/FVC ratio (post bronchodilator) ≤70%&#xD;
&#xD;
          -  FEV1 (post bronchodilator) ≤ 65%&#xD;
&#xD;
          -  Presence or high likelihood of chronic cough and sputum production defined as one of&#xD;
             the following:&#xD;
&#xD;
        Presence of chronic cough and sputum will be defined by responses to the first two&#xD;
        questions on the SGRQ. Subjects who respond positively to both question 1 (cough) and&#xD;
        question 2 (sputum) on the SGRQ as either &quot;several days per week&quot; or &quot;almost every day&quot;&#xD;
        will be eligible.&#xD;
&#xD;
        COPD exacerbation within the previous 12 months defined as taking antibiotics and/or&#xD;
        prednisone for respiratory symptoms, hospitalization or emergency department visit for&#xD;
        respiratory illness.&#xD;
&#xD;
          -  Current or former smoker with lifetime cigarette consumption of &gt; 10 pack-years&#xD;
&#xD;
          -  Negative serum pregnancy test at the baseline visit if patient is a pre-menopausal&#xD;
             female (menopause defined as absence of a menstrual cycle in the last 12 months)&#xD;
&#xD;
          -  Must be fluent in speaking the English language&#xD;
&#xD;
          -  Have a minimum of four teeth&#xD;
&#xD;
        Exclusion Criteria:&#xD;
&#xD;
          -  Not fully recovered for at least 30 days from a COPD exacerbation.&#xD;
&#xD;
          -  Treated with antibiotics in the last 2 months.&#xD;
&#xD;
          -  The presence of dentures (full plate).&#xD;
&#xD;
          -  Active oral infection being treated by health care professional.&#xD;
&#xD;
          -  Current use of chlorhexidine or over-the-counter mouth washes in the last 2 months.&#xD;
&#xD;
          -  Known allergy or sensitivity to chlorhexidine&#xD;
&#xD;
          -  Unstable cardiac disease&#xD;
&#xD;
          -  Clinical diagnosis of asthma, bronchiectasis, cystic fibrosis, or severe alpha-1&#xD;
             antitrypsin deficiency&#xD;
&#xD;
          -  Active lung cancer or history of lung cancer if it has been less than 2 years since&#xD;
             lung resection or other treatment. If history of lung cancer, must have no evidence of&#xD;
             recurrence in the 2 years preceding the baseline visit.&#xD;
      </textblock>
    </criteria>
    <gender>All</gender>
    <minimum_age>40 Years</minimum_age>
    <maximum_age>85 Years</maximum_age>
    <healthy_volunteers>No</healthy_volunteers>
  </eligibility>
  <overall_official>
    <last_name>Chris Wendt, MD</last_name>
    <role>Principal Investigator</role>
    <affiliation>VA Medical Center</affiliation>
  </overall_official>
  <location>
    <facility>
      <name>VA Medical Center</name>
      <address>
        <city>Minneapolis</city>
        <state>Minnesota</state>
        <zip>55417</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location_countries>
    <country>United States</country>
  </location_countries>
  <verification_date>December 2020</verification_date>
  <study_first_submitted>September 25, 2014</study_first_submitted>
  <study_first_submitted_qc>September 29, 2014</study_first_submitted_qc>
  <study_first_posted type="Estimate">September 30, 2014</study_first_posted>
  <results_first_submitted>December 3, 2020</results_first_submitted>
  <results_first_submitted_qc>December 3, 2020</results_first_submitted_qc>
  <results_first_posted type="Actual">December 29, 2020</results_first_posted>
  <last_update_submitted>December 3, 2020</last_update_submitted>
  <last_update_submitted_qc>December 3, 2020</last_update_submitted_qc>
  <last_update_posted type="Actual">December 29, 2020</last_update_posted>
  <responsible_party>
    <responsible_party_type>Sponsor</responsible_party_type>
  </responsible_party>
  <keyword>COPD</keyword>
  <keyword>Bacteria</keyword>
  <condition_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Lung Diseases</mesh_term>
    <mesh_term>Lung Diseases, Obstructive</mesh_term>
    <mesh_term>Pulmonary Disease, Chronic Obstructive</mesh_term>
  </condition_browse>
  <intervention_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Chlorhexidine</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>March 31, 2014</document_date>
      <document_url>https://ClinicalTrials.gov/ProvidedDocs/88/NCT02252588/Prot_SAP_000.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>February 15, 2017</document_date>
      <document_url>https://ClinicalTrials.gov/ProvidedDocs/88/NCT02252588/ICF_001.pdf</document_url>
    </provided_document>
  </provided_document_section>

  <clinical_results>

    <participant_flow>
      <group_list>
        <group group_id="P1">
          <title>Chlorhexidine</title>
          <description>Oral Rinse&#xD;
Chlorhexidine: Oral Rinse&#xD;
Placebo: Oral Rinse</description>
        </group>
        <group group_id="P2">
          <title>Placebo</title>
          <description>Oral Rinse&#xD;
Chlorhexidine: Oral Rinse&#xD;
Placebo: Oral Rinse</description>
        </group>
      </group_list>
      <period_list>
        <period>
          <title>Overall Study</title>
          <milestone_list>
            <milestone>
              <title>STARTED</title>
              <participants_list>
                <participants group_id="P1" count="24"/>
                <participants group_id="P2" count="20"/>
              </participants_list>
            </milestone>
            <milestone>
              <title>COMPLETED</title>
              <participants_list>
                <participants group_id="P1" count="20"/>
                <participants group_id="P2" count="20"/>
              </participants_list>
            </milestone>
            <milestone>
              <title>NOT COMPLETED</title>
              <participants_list>
                <participants group_id="P1" count="4"/>
                <participants group_id="P2" count="0"/>
              </participants_list>
            </milestone>
          </milestone_list>
          <drop_withdraw_reason_list>
            <drop_withdraw_reason>
              <title>Withdrawal by Subject</title>
              <participants_list>
                <participants group_id="P1" count="4"/>
                <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>Chlorhexidine</title>
          <description>Oral Rinse&#xD;
Chlorhexidine: Oral Rinse&#xD;
Placebo: Oral Rinse</description>
        </group>
        <group group_id="B2">
          <title>Placebo</title>
          <description>Oral Rinse&#xD;
Chlorhexidine: Oral Rinse&#xD;
Placebo: Oral Rinse</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="24"/>
            <count group_id="B2" value="20"/>
            <count group_id="B3" value="44"/>
          </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="5"/>
                    <measurement group_id="B2" value="5"/>
                    <measurement group_id="B3" value="10"/>
                  </measurement_list>
                </category>
                <category>
                  <title>&gt;=65 years</title>
                  <measurement_list>
                    <measurement group_id="B1" value="19"/>
                    <measurement group_id="B2" value="15"/>
                    <measurement group_id="B3" value="34"/>
                  </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="22"/>
                    <measurement group_id="B2" value="1"/>
                    <measurement group_id="B3" value="23"/>
                  </measurement_list>
                </category>
                <category>
                  <title>Male</title>
                  <measurement_list>
                    <measurement group_id="B1" value="2"/>
                    <measurement group_id="B2" value="19"/>
                    <measurement group_id="B3" value="21"/>
                  </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="1"/>
                    <measurement group_id="B2" value="0"/>
                    <measurement group_id="B3" value="1"/>
                  </measurement_list>
                </category>
                <category>
                  <title>Asian</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>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_list>
                </category>
                <category>
                  <title>Black or African American</title>
                  <measurement_list>
                    <measurement group_id="B1" value="0"/>
                    <measurement group_id="B2" value="1"/>
                    <measurement group_id="B3" value="1"/>
                  </measurement_list>
                </category>
                <category>
                  <title>White</title>
                  <measurement_list>
                    <measurement group_id="B1" value="23"/>
                    <measurement group_id="B2" value="19"/>
                    <measurement group_id="B3" value="42"/>
                  </measurement_list>
                </category>
                <category>
                  <title>More than one race</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>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_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="24"/>
                    <measurement group_id="B2" value="20"/>
                    <measurement group_id="B3" value="44"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </measure_list>
    </baseline>

    <outcome_list>
      <outcome>
        <type>Primary</type>
        <title>Change in Sputum Bacteria Biomass</title>
        <description>Samples underwent DNA extraction and 16S rRNA quantification and 16S rRNA V4 MiSeq sequencing was performed at the University of Minnesota Genomics Center. The biomass was the number of bacteria as measured by 16S rRNA copy number. To adjust biomass for the size of the sputum sample, raw counts were normalized by dividing by the sample volume or mass.</description>
        <time_frame>Baseline, 8 weeks</time_frame>
        <group_list>
          <group group_id="O1">
            <title>Chlorhexidine</title>
            <description>Oral Rinse&#xD;
Chlorhexidine: Oral Rinse&#xD;
Placebo: Oral Rinse</description>
          </group>
          <group group_id="O2">
            <title>Placebo</title>
            <description>Oral Rinse&#xD;
Chlorhexidine: Oral Rinse&#xD;
Placebo: Oral Rinse</description>
          </group>
        </group_list>
        <measure>
          <title>Change in Sputum Bacteria Biomass</title>
          <description>Samples underwent DNA extraction and 16S rRNA quantification and 16S rRNA V4 MiSeq sequencing was performed at the University of Minnesota Genomics Center. The biomass was the number of bacteria as measured by 16S rRNA copy number. To adjust biomass for the size of the sputum sample, raw counts were normalized by dividing by the sample volume or mass.</description>
          <units>log10 molecules/uL/mL</units>
          <param>Mean</param>
          <dispersion>Standard Deviation</dispersion>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="20"/>
                <count group_id="O2" value="20"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="-0.24" spread="11.7"/>
                    <measurement group_id="O2" value="-0.14" spread="0.32"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </outcome>
      <outcome>
        <type>Secondary</type>
        <title>Breathlessness, Cough, and Sputum Scale (BCSS)</title>
        <description>The Breathlessness, Cough, and Sputum Scale (BCSS) is a brief, three-item, patient-reported outcome measure in which each of the three symptoms assessed by the measure is represented by a single item. Patients are asked to evaluate each symptom/item on a 5-point Likert-type scale, ranging from 0 to 4. Total scores range from 0 to 12 with higher scores indicating a more severe manifestation of the symptom.</description>
        <time_frame>Baseline, 8 weeks</time_frame>
        <group_list>
          <group group_id="O1">
            <title>Chlorhexidine</title>
            <description>Oral Rinse&#xD;
Chlorhexidine: Oral Rinse&#xD;
Placebo: Oral Rinse</description>
          </group>
          <group group_id="O2">
            <title>Placebo</title>
            <description>Oral Rinse&#xD;
Chlorhexidine: Oral Rinse&#xD;
Placebo: Oral Rinse</description>
          </group>
        </group_list>
        <measure>
          <title>Breathlessness, Cough, and Sputum Scale (BCSS)</title>
          <description>The Breathlessness, Cough, and Sputum Scale (BCSS) is a brief, three-item, patient-reported outcome measure in which each of the three symptoms assessed by the measure is represented by a single item. Patients are asked to evaluate each symptom/item on a 5-point Likert-type scale, ranging from 0 to 4. Total scores range from 0 to 12 with higher scores indicating a more severe manifestation of the symptom.</description>
          <units>units on a scale</units>
          <param>Mean</param>
          <dispersion>Standard Deviation</dispersion>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="20"/>
                <count group_id="O2" value="20"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="0.42" spread="1.24"/>
                    <measurement group_id="O2" value="-0.38" spread="1.13"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </outcome>
      <outcome>
        <type>Secondary</type>
        <title>Change in St George Respiratory Quotient (SGRQ)</title>
        <description>The St George Respiratory Quotient (SGRQ) contains 50 items measuring symptoms of and activities affected by obstructive airway disease. Total score is a sum of item scores and ranges from 0 to 100, with higher scores indicating more limitations. The minimally significant difference is 4.</description>
        <time_frame>baseline, 8 weeks</time_frame>
        <group_list>
          <group group_id="O1">
            <title>Chlorhexidine</title>
            <description>Oral Rinse&#xD;
Chlorhexidine: Oral Rinse&#xD;
Placebo: Oral Rinse</description>
          </group>
          <group group_id="O2">
            <title>Placebo</title>
            <description>Oral Rinse&#xD;
Chlorhexidine: Oral Rinse&#xD;
Placebo: Oral Rinse</description>
          </group>
        </group_list>
        <measure>
          <title>Change in St George Respiratory Quotient (SGRQ)</title>
          <description>The St George Respiratory Quotient (SGRQ) contains 50 items measuring symptoms of and activities affected by obstructive airway disease. Total score is a sum of item scores and ranges from 0 to 100, with higher scores indicating more limitations. The minimally significant difference is 4.</description>
          <units>score on a scale</units>
          <param>Mean</param>
          <dispersion>Standard Deviation</dispersion>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="20"/>
                <count group_id="O2" value="20"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="-4.7" spread="8"/>
                    <measurement group_id="O2" value="1.7" spread="8.9"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </outcome>
    </outcome_list>

    <reported_events>
      <time_frame>8 weeks</time_frame>
      <group_list>
        <group group_id="E1">
          <title>Chlorhexidine</title>
          <description>Oral Rinse&#xD;
Chlorhexidine: Oral Rinse&#xD;
Placebo: Oral Rinse</description>
        </group>
        <group group_id="E2">
          <title>Placebo</title>
          <description>Oral Rinse&#xD;
Chlorhexidine: Oral Rinse&#xD;
Placebo: Oral Rinse</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="24"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="20"/>
              </event>
              <event>
                <sub_title>Total, serious adverse events</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="24"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="20"/>
              </event>
            </event_list>
          </category>
        </category_list>
      </serious_events>
      <other_events>
        <frequency_threshold>0</frequency_threshold>
        <default_assessment>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="2" subjects_at_risk="24"/>
                <counts group_id="E2" subjects_affected="4" subjects_at_risk="20"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>General disorders</title>
            <event_list>
              <event>
                <sub_title>Other oral side effects</sub_title>
                <counts group_id="E1" events="2" subjects_affected="2" subjects_at_risk="24"/>
                <counts group_id="E2" events="0" subjects_affected="0" subjects_at_risk="20"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Respiratory, thoracic and mediastinal disorders</title>
            <event_list>
              <event>
                <sub_title>Congestion, Sinus Infection, and Cough</sub_title>
                <counts group_id="E1" events="0" subjects_affected="0" subjects_at_risk="24"/>
                <counts group_id="E2" events="3" subjects_affected="3" subjects_at_risk="20"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Skin and subcutaneous tissue disorders</title>
            <event_list>
              <event>
                <sub_title>Irritation and/or sores of the lining of the mouth</sub_title>
                <counts group_id="E1" events="0" subjects_affected="0" subjects_at_risk="24"/>
                <counts group_id="E2" events="1" subjects_affected="1" subjects_at_risk="20"/>
              </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>
    <point_of_contact>
      <name_or_title>Christine Wendt, MD</name_or_title>
      <organization>University of Minnesota</organization>
      <phone>612-624-0999</phone>
      <email>wendt005@umn.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/NCT02252588
org study id: 4526
nct id: NCT02252588
lead sponsor: 
collaborator: 
collaborator: 
has dmc: No
Determine the effect of twice-daily chlorhexidine oral rinse on oral and lung microbiota
      biomass in subjects with chronic obstructive pulmonary disease (COPD) with chronic
      bronchitis. Our primary outcome will be to compare the microbiota biomass (number of bacteria
      as measured by 16S rRNA copy number) of induced sputum and the oral cavity before and after 8
      weeks of twice-daily chlorhexidine oral rinse (n=25) compared to controls (n=25) using qPCR
      and next-generation sequencing of the bacterial 16S rRNA gene comparing total bacterial
      biomass
Our hypothesis is that 8 weeks of chlorhexidine oral rinse will decrease microbiota biomass
      compared to baseline and those on placebo. Furthermore, we hypothesize that chlorhexidine
      treatment will: i) decrease lung and oral microbiota diversity; ii) alter microbiota
      taxonomic composition in the lung and oral cavity; iii) decrease systemic inflammation as
      measured by blood high sensitivity C-reactive protein (hsCRP), fibrinogen and leukocyte
      count; and iv) demonstrate a trend towards improvement in respiratory health status as
      measured by the Breathlessness, Cough, and Sputum Scale (BCSS)[1, 2] and St. George's
      Respiratory Questionnaire (SGRQ).

      Subaim 1: Determine if chlorhexidine alters the lung and oral rinse microbiota diversity and
      taxonomic composition. Our hypothesis is that chlorhexidine oral rinse will decrease the
      diversity (Shannon and inverse Simpson diversity indices) and taxonomic composition of both
      oral and lung microbiota compared to those on placebo as determined by next-generation
      sequencing of the bacterial 16S rRNA gene.

      Subaim 2: Determine the impact of chlorhexidine on systemic inflammation. Our hypothesis is
      that the decrease in lung microbiota biomass is associated with a decrease in systemic
      inflammation as measured by blood hsCRP, fibrinogen, and leukocyte count.

      Subaim 3: Determine if respiratory symptoms associate with the lung microbiota biomass. Our
      hypothesis is that chlorhexidine will demonstrate improved respiratory health status as
      measured by the BCSS and SGRQ.
allocation: Randomized
intervention model: Parallel Assignment
primary purpose: Basic Science
masking: Double (Participant, Investigator)
measure: Change in Sputum Bacteria Biomass
time frame: Baseline, 8 weeks
description: Samples underwent DNA extraction and 16S rRNA quantification and 16S rRNA V4 MiSeq sequencing was performed at the University of Minnesota Genomics Center. The biomass was the number of bacteria as measured by 16S rRNA copy number. To adjust biomass for the size of the sputum sample, raw counts were normalized by dividing by the sample volume or mass.
measure: Breathlessness, Cough, and Sputum Scale (BCSS)
time frame: Baseline, 8 weeks
description: The Breathlessness, Cough, and Sputum Scale (BCSS) is a brief, three-item, patient-reported outcome measure in which each of the three symptoms assessed by the measure is represented by a single item. Patients are asked to evaluate each symptom/item on a 5-point Likert-type scale, ranging from 0 to 4. Total scores range from 0 to 12 with higher scores indicating a more severe manifestation of the symptom.
measure: Change in St George Respiratory Quotient (SGRQ)
time frame: baseline, 8 weeks
description: The St George Respiratory Quotient (SGRQ) contains 50 items measuring symptoms of and activities affected by obstructive airway disease. Total score is a sum of item scores and ranges from 0 to 100, with higher scores indicating more limitations. The minimally significant difference is 4.
arm group label: Chlorhexidine
arm group type: Experimental
description: Oral Rinse
arm group label: Placebo
arm group type: Placebo Comparator
description: Oral Rinse
intervention type: Drug
intervention name: Chlorhexidine
description: Oral Rinse
arm group label: Chlorhexidine
arm group label: Placebo
intervention type: Other
intervention name: Placebo
description: Oral Rinse
arm group label: Chlorhexidine
arm group label: Placebo
criteria: 
gender: All
minimum age: 40 Years
maximum age: 85 Years
healthy volunteers: No
last name: Chris Wendt, MD
role: Principal Investigator
affiliation: VA Medical Center
facility: 
country: United States
responsible party type: Sponsor
mesh term: Lung Diseases
mesh term: Lung Diseases, Obstructive
mesh term: Pulmonary Disease, Chronic Obstructive
mesh term: Chlorhexidine
provided document: 
provided document: 
participant flow: 
baseline: 
outcome list: 
reported events: 
certain agreements: 
point of contact: 