<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/NCT02218320</url>
  </required_header>
  <id_info>
    <org_study_id>14-1647</org_study_id>
    <nct_id>NCT02218320</nct_id>
  </id_info>
  <brief_title>Comparison of Virologic and Immunologic Responses to Raltegravir and Dolutegravir in the Gastrointestinal Tract of HIV-Positive Adults</brief_title>
  <official_title>A Phase IV, Open-Label Study to Compare Virologic and Immunologic Responses to Raltegravir and Dolutegravir in the Gastrointestinal Tract of HIV-Positive Men and Women</official_title>
  <sponsors>
    <lead_sponsor>
      <agency>University of North Carolina, Chapel Hill</agency>
      <agency_class>Other</agency_class>
    </lead_sponsor>
    <collaborator>
      <agency>Merck Sharp &amp; Dohme LLC</agency>
      <agency_class>Industry</agency_class>
    </collaborator>
  </sponsors>
  <source>University of North Carolina, Chapel Hill</source>
  <oversight_info>
    <has_dmc>No</has_dmc>
    <is_fda_regulated_drug>Yes</is_fda_regulated_drug>
    <is_fda_regulated_device>No</is_fda_regulated_device>
    <is_us_export>No</is_us_export>
  </oversight_info>
  <brief_summary>
    <textblock>
      This is a Phase IV, open label, observational study to compare the gastrointestinal tissue&#xD;
      concentrations, inflammatory response, and viral replication of two integrase-inhibitors,&#xD;
      raltegravir and dolutegravir, in HIV-infected volunteers who are virologically suppressed in&#xD;
      blood plasma. The study will be comprised of 20 HIV-infected volunteers who will be enrolled&#xD;
      equally into two groups. Group A will consist of 10 subjects receiving an antiretroviral&#xD;
      regimen of tenofovir, emtricitabine, and raltegravir, and Group B will consist of 10 subjects&#xD;
      receiving an antiretroviral regimen of tenofovir, emtricitabine, and dolutegravir.&#xD;
      Participants will provide small pieces of tissue, or biopsies, which will be taken from three&#xD;
      distinct locations of the large intestine during a colonoscopy procedure. These biopsies will&#xD;
      be used to measure the amount of raltegravir or dolutegravir, HIV virus, and inflammatory&#xD;
      markers present in the gastrointestinal tract.&#xD;
    </textblock>
  </brief_summary>
  <detailed_description>
    <textblock>
      Purpose: To compare virologic and immunologic responses to raltegravir and dolutegravir in&#xD;
      the gastrointestinal tract of HIV-positive men and women&#xD;
&#xD;
      Participants: Twenty HIV-infected volunteers will be enrolled equally into two groups. Group&#xD;
      A will consist of subjects receiving an antiretroviral regimen of raltegravir, tenofovir, and&#xD;
      emtricitabine and Group B will consist of subjects receiving an antiretroviral regimen of&#xD;
      dolutegravir, tenofovir, and emtricitabine.&#xD;
&#xD;
      Procedures (methods): This is a Phase IV, open label study to compare the gastrointestinal&#xD;
      tissue concentrations, cytokine response, and viral replication in gut-associated lymphoid&#xD;
      tissue of two integrase-inhibitors in HIV-infected volunteers who are virologically&#xD;
      suppressed in blood plasma. Subjects will undergo an observed bowel preparation, followed by&#xD;
      a colonoscopy in which tissue will be obtained by a board-certified gastroenterologist from&#xD;
      the terminal ileum/ascending colon, splenic flexture, and rectum/sigmoid colon. Blood plasma&#xD;
      will be collected immediately prior to collection of tissue samples.&#xD;
    </textblock>
  </detailed_description>
  <overall_status>Completed</overall_status>
  <start_date>October 2014</start_date>
  <completion_date type="Actual">October 2015</completion_date>
  <primary_completion_date type="Actual">October 2015</primary_completion_date>
  <study_type>Observational</study_type>
  <has_expanded_access>No</has_expanded_access>
  <study_design_info>
    <observational_model>Other</observational_model>
    <time_perspective>Prospective</time_perspective>
  </study_design_info>
  <primary_outcome>
    <measure>Rectal Tissue Concentrations of Ralegravir and Dolutegravir</measure>
    <time_frame>2 to 6 hours post dose</time_frame>
  </primary_outcome>
  <primary_outcome>
    <measure>RNA Concentrations From Gastrointestinal Tissues</measure>
    <time_frame>2 to 6 hours post dose</time_frame>
    <description>We measured RNA concentrations in copies/1000cells for both drug groups</description>
  </primary_outcome>
  <primary_outcome>
    <measure>Percentage of Total CD8+ T-cells With CCR5 Expression</measure>
    <time_frame>2 to 6 hours post dose</time_frame>
    <description>Local immunologic markers in gastrointestinal tract tissues</description>
  </primary_outcome>
  <number_of_groups>2</number_of_groups>
  <enrollment type="Actual">20</enrollment>
  <condition>Human Immunodeficiency Virus</condition>
  <arm_group>
    <arm_group_label>Group A</arm_group_label>
    <description>Ten HIV-infected adults will be in Group A and take the HIV medication raltegravir in combination with tenofovir and emtricitabine as their provider-prescribed antiretroviral regimen.</description>
  </arm_group>
  <arm_group>
    <arm_group_label>Group B</arm_group_label>
    <description>Ten HIV-infected adults will be in Group B and take the HIV medication dolutegravir in combination with tenofovir and emtricitabine as their provider-prescribed antiretroviral regimen.</description>
  </arm_group>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>Raltegravir</intervention_name>
    <arm_group_label>Group A</arm_group_label>
    <other_name>Isentress ®</other_name>
  </intervention>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>Dolutegravir</intervention_name>
    <arm_group_label>Group B</arm_group_label>
    <other_name>Tivicay ®</other_name>
  </intervention>
  <intervention>
    <intervention_type>Procedure</intervention_type>
    <intervention_name>Colonoscopy with biopsy</intervention_name>
    <description>This procedure is not standard of care for patients receiving combination antiretroviral therapy (cART), but is necessary to obtain tissue samples.</description>
    <arm_group_label>Group A</arm_group_label>
    <arm_group_label>Group B</arm_group_label>
  </intervention>
  <eligibility>
    <study_pop>
      <textblock>
        Subjects will be recruited from University of North Carolina Infectious Diseases Clinic.&#xD;
      </textblock>
    </study_pop>
    <sampling_method>Non-Probability Sample</sampling_method>
    <criteria>
      <textblock>
        Inclusion Criteria:&#xD;
&#xD;
          -  Healthy HIV-positive adults aged 18-65, inclusive on the date of screening, with&#xD;
             documentation of at least one positive HIV test. Healthy is defined as no clinically&#xD;
             relevant abnormalities that would interfere with the interpretation of results, or&#xD;
             pose unnecessary risk onto volunteers due to study procedures.&#xD;
&#xD;
          -  Receiving an antiretroviral regimen containing tenofovir+emtricitabine with&#xD;
             raltegravir (Group A) or dolutegravir (Group B) for &gt; 3 months, with blood plasma HIV&#xD;
             RNA &lt; 50copies/mL for at least 4 weeks, or a 2 log decrease in baseline blood plasma&#xD;
             HIV RNA.&#xD;
&#xD;
          -  Evidence of a personally signed and dated informed consent document indicating that&#xD;
             the subject has been informed of all pertinent aspects of the trial.&#xD;
&#xD;
          -  Documentation of at least 80% adherence to antiretroviral regimen, through clinician&#xD;
             or self-report, with no missed doses in the 3 days prior to the inpatient visit.&#xD;
&#xD;
          -  Willing and able to comply with scheduled visits, treatment plan, laboratory tests,&#xD;
             and other trial procedures.&#xD;
&#xD;
          -  Women of childbearing potential must be utilizing at least one acceptable form of&#xD;
             birth control.&#xD;
&#xD;
        Exclusion Criteria:&#xD;
&#xD;
          -  Evidence or history of clinically significant hematological, renal, endocrine,&#xD;
             pulmonary, gastrointestinal, cardiovascular, hepatic, psychiatric, or neurologic&#xD;
             disease that would pose unnecessary risk or interfere with study results. Subjects&#xD;
             will be excluded for any condition that would increase risk from sedation, endoscopy,&#xD;
             or biopsy.&#xD;
&#xD;
          -  Subjects with a history of having a gastrectomy, colostomy, ileostomy, or any other&#xD;
             clinically significant procedure altering the gastrointestinal tract, or any condition&#xD;
             possibly affecting drug absorption.&#xD;
&#xD;
          -  Subjects with inflammatory bowel diseases (ulcerative colitis or Crohn's disease).&#xD;
&#xD;
          -  Female subjects who are currently pregnant or breastfeeding, or planning to become&#xD;
             pregnant during the study period.&#xD;
&#xD;
          -  Subjects who are unwilling to refrain from insertion of medical/recreation devices and&#xD;
             products into the rectum, and from receptive anal intercourse, for 72 hours before&#xD;
             inpatient study visit and through 7 days after the last biopsy unless instructed&#xD;
             otherwise by the investigators.&#xD;
&#xD;
          -  A positive urine drug screen.&#xD;
&#xD;
          -  Untreated rectal sexually transmitted infection at screening.&#xD;
&#xD;
          -  Treatment with an investigational drug within 2 months preceding study enrollment.&#xD;
&#xD;
          -  Participated in a gastrointestinal biopsy study in the 3 months preceding study&#xD;
             enrollment.&#xD;
&#xD;
          -  Participants with a history of clotting or bleeding disorders.&#xD;
&#xD;
          -  Participants with a history of abnormal reaction to, or complication from, conscious&#xD;
             sedation or anesthesia&#xD;
&#xD;
          -  Subjects who are unwilling or unable to comply with the following dietary restrictions&#xD;
             in regard to study procedures, including a clear liquid diet during bowel preparation&#xD;
             and a period of NPO (nil per os) prior to the colonoscopy. While confined, the total&#xD;
             daily nutritional composition will be 50% carbohydrate, 15% protein, and 35% fat. The&#xD;
             daily caloric intake should not exceed 3200kcal.&#xD;
&#xD;
          -  Abnormalities of the colorectal mucosa, or significant colorectal symptom(s), which in&#xD;
             the opinion of the clinician represents a contraindication to biopsy (including but&#xD;
             not limited to presence of any unresolved injury, infectious or inflammatory condition&#xD;
             of the local mucosa, and presence of symptomatic external hemorrhoids).&#xD;
&#xD;
          -  Any other reason or condition that in the judgment of the investigators would make&#xD;
             participation in the study unsafe, complicate interpretation of study outcome data, or&#xD;
             otherwise interfere with achieving the study objectives.&#xD;
      </textblock>
    </criteria>
    <gender>All</gender>
    <minimum_age>18 Years</minimum_age>
    <maximum_age>65 Years</maximum_age>
    <healthy_volunteers>No</healthy_volunteers>
  </eligibility>
  <overall_official>
    <last_name>Angela DM Kashuba, PharmD</last_name>
    <role>Principal Investigator</role>
    <affiliation>University of North Carolina, Chapel Hill</affiliation>
  </overall_official>
  <location>
    <facility>
      <name>Clinical and Translational Research Center, UNC Hospitals</name>
      <address>
        <city>Chapel Hill</city>
        <state>North Carolina</state>
        <zip>27599</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location_countries>
    <country>United States</country>
  </location_countries>
  <verification_date>April 2017</verification_date>
  <study_first_submitted>August 13, 2014</study_first_submitted>
  <study_first_submitted_qc>August 14, 2014</study_first_submitted_qc>
  <study_first_posted type="Estimate">August 18, 2014</study_first_posted>
  <results_first_submitted>February 27, 2017</results_first_submitted>
  <results_first_submitted_qc>February 6, 2018</results_first_submitted_qc>
  <results_first_posted type="Actual">October 29, 2018</results_first_posted>
  <last_update_submitted>December 4, 2018</last_update_submitted>
  <last_update_submitted_qc>December 4, 2018</last_update_submitted_qc>
  <last_update_posted type="Actual">December 26, 2018</last_update_posted>
  <responsible_party>
    <responsible_party_type>Sponsor</responsible_party_type>
  </responsible_party>
  <keyword>HIV</keyword>
  <keyword>Gut-associated lymphoid tissue</keyword>
  <keyword>raltegravir</keyword>
  <keyword>Isentress</keyword>
  <keyword>dolutegravir</keyword>
  <keyword>Tivicay</keyword>
  <keyword>pharmacodynamics</keyword>
  <condition_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Acquired Immunodeficiency Syndrome</mesh_term>
    <mesh_term>HIV Infections</mesh_term>
  </condition_browse>
  <intervention_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Raltegravir Potassium</mesh_term>
    <mesh_term>Dolutegravir</mesh_term>
  </intervention_browse>
  <patient_data>
    <sharing_ipd>No</sharing_ipd>
  </patient_data>

  <clinical_results>

    <participant_flow>
      <recruitment_details>Recruitment began upon IRB approval. Patients were enrolled from December 2014 to October 2015, at which time data analysis ensued. Enrollment continued until 20 subjects completed all study procedures. Patients were recruited from the Infectious Disease clinics associated with the University of North Carolina at Chapel Hill.</recruitment_details>
      <pre_assignment_details>After informed consent, all patients underwent a screening visit to determine eligibility. This visit had to occur within the 6 weeks prior to study enrollment. Patients were enrolled into the group that matched their treatment regimen.</pre_assignment_details>
      <group_list>
        <group group_id="P1">
          <title>Group A</title>
          <description>Ten HIV-infected adults will be in Group A and take the HIV medication raltegravir in combination with tenofovir and emtricitabine as their provider-prescribed antiretroviral regimen.&#xD;
Raltegravir&#xD;
Colonoscopy with biopsy: This procedure is not standard of care for patients receiving combination antiretroviral therapy (cART), but is necessary to obtain tissue samples.</description>
        </group>
        <group group_id="P2">
          <title>Group B</title>
          <description>Ten HIV-infected adults will be in Group B and take the HIV medication dolutegravir in combination with tenofovir and emtricitabine as their provider-prescribed antiretroviral regimen.&#xD;
Dolutegravir&#xD;
Colonoscopy with biopsy: This procedure is not standard of care for patients receiving combination antiretroviral therapy (cART), but is necessary to obtain tissue samples.</description>
        </group>
      </group_list>
      <period_list>
        <period>
          <title>Overall Study</title>
          <milestone_list>
            <milestone>
              <title>STARTED</title>
              <participants_list>
                <participants group_id="P1" count="10">First participant visit on this arm Dec 2014</participants>
                <participants group_id="P2" count="10">First participant contact on this arm was December 2014</participants>
              </participants_list>
            </milestone>
            <milestone>
              <title>COMPLETED</title>
              <participants_list>
                <participants group_id="P1" count="10">Last participant contact on this arm was June 2015</participants>
                <participants group_id="P2" count="10">Last participant contact on this arm was October 2015</participants>
              </participants_list>
            </milestone>
            <milestone>
              <title>NOT COMPLETED</title>
              <participants_list>
                <participants group_id="P1" count="0"/>
                <participants group_id="P2" count="0"/>
              </participants_list>
            </milestone>
          </milestone_list>
        </period>
      </period_list>
    </participant_flow>

    <baseline>
      <group_list>
        <group group_id="B1">
          <title>Group A</title>
          <description>Ten HIV-infected adults will be in Group A and take the HIV medication raltegravir in combination with tenofovir and emtricitabine as their provider-prescribed antiretroviral regimen.&#xD;
Raltegravir&#xD;
Colonoscopy with biopsy: This procedure is not standard of care for patients receiving combination antiretroviral therapy (cART), but is necessary to obtain tissue samples. All 10 subjects underwent a bowel prep with subsequent colonoscopy to obtain tissue samples.</description>
        </group>
        <group group_id="B2">
          <title>Group B</title>
          <description>Ten HIV-infected adults will be in Group B and take the HIV medication dolutegravir in combination with tenofovir and emtricitabine as their provider-prescribed antiretroviral regimen.&#xD;
Dolutegravir&#xD;
Colonoscopy with biopsy: This procedure is not standard of care for patients receiving combination antiretroviral therapy (cART), but is necessary to obtain tissue samples. All 10 subjects underwent a bowel prep with subsequent colonoscopy to obtain tissue samples.</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="10"/>
            <count group_id="B2" value="10"/>
            <count group_id="B3" value="20"/>
          </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="10"/>
                    <measurement group_id="B2" value="10"/>
                    <measurement group_id="B3" value="20"/>
                  </measurement_list>
                </category>
                <category>
                  <title>&gt;=65 years</title>
                  <measurement_list>
                    <measurement group_id="B1" value="0"/>
                    <measurement group_id="B2" value="0"/>
                    <measurement group_id="B3" value="0"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
        <measure>
          <title>Age</title>
          <units>years</units>
          <param>Median</param>
          <dispersion>Full Range</dispersion>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="B1" value="54.5" lower_limit="48" upper_limit="64"/>
                    <measurement group_id="B2" value="49.5" lower_limit="32" upper_limit="56"/>
                    <measurement group_id="B3" value="52.5" lower_limit="32" upper_limit="64"/>
                  </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="4"/>
                    <measurement group_id="B2" value="1"/>
                    <measurement group_id="B3" value="5"/>
                  </measurement_list>
                </category>
                <category>
                  <title>Male</title>
                  <measurement_list>
                    <measurement group_id="B1" value="6"/>
                    <measurement group_id="B2" value="9"/>
                    <measurement group_id="B3" value="15"/>
                  </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="0"/>
                    <measurement group_id="B2" value="0"/>
                    <measurement group_id="B3" value="0"/>
                  </measurement_list>
                </category>
                <category>
                  <title>Not Hispanic or Latino</title>
                  <measurement_list>
                    <measurement group_id="B1" value="10"/>
                    <measurement group_id="B2" value="10"/>
                    <measurement group_id="B3" value="20"/>
                  </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>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_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="7"/>
                    <measurement group_id="B2" value="5"/>
                    <measurement group_id="B3" value="12"/>
                  </measurement_list>
                </category>
                <category>
                  <title>White</title>
                  <measurement_list>
                    <measurement group_id="B1" value="3"/>
                    <measurement group_id="B2" value="3"/>
                    <measurement group_id="B3" value="6"/>
                  </measurement_list>
                </category>
                <category>
                  <title>More than one race</title>
                  <measurement_list>
                    <measurement group_id="B1" value="0"/>
                    <measurement group_id="B2" value="2"/>
                    <measurement group_id="B3" value="2"/>
                  </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>Count of Participants</param>
          <class_list>
            <class>
              <title>United States</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="B1" value="10"/>
                    <measurement group_id="B2" value="10"/>
                    <measurement group_id="B3" value="20"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </measure_list>
    </baseline>

    <outcome_list>
      <outcome>
        <type>Primary</type>
        <title>Rectal Tissue Concentrations of Ralegravir and Dolutegravir</title>
        <time_frame>2 to 6 hours post dose</time_frame>
        <group_list>
          <group group_id="O1">
            <title>Group A</title>
            <description>Ten HIV-infected adults will be in Group A and take the HIV medication raltegravir in combination with tenofovir and emtricitabine as their provider-prescribed antiretroviral regimen.&#xD;
Raltegravir&#xD;
Colonoscopy with biopsy: This procedure is not standard of care for patients receiving combination antiretroviral therapy (cART), but is necessary to obtain tissue samples.</description>
          </group>
          <group group_id="O2">
            <title>Group B</title>
            <description>Ten HIV-infected adults will be in Group B and take the HIV medication dolutegravir in combination with tenofovir and emtricitabine as their provider-prescribed antiretroviral regimen.&#xD;
Dolutegravir&#xD;
Colonoscopy with biopsy: This procedure is not standard of care for patients receiving combination antiretroviral therapy (cART), but is necessary to obtain tissue samples.</description>
          </group>
        </group_list>
        <measure>
          <title>Rectal Tissue Concentrations of Ralegravir and Dolutegravir</title>
          <units>ng/g</units>
          <param>Median</param>
          <dispersion>Full Range</dispersion>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="10"/>
                <count group_id="O2" value="10"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="5308" lower_limit="3938" upper_limit="19600"/>
                    <measurement group_id="O2" value="810" lower_limit="510" upper_limit="1408"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
        <analysis_list>
          <analysis>
            <group_id_list>
              <group_id>O1</group_id>
              <group_id>O2</group_id>
            </group_id_list>
            <non_inferiority_type>Other</non_inferiority_type>
            <p_value>1.0</p_value>
            <method>Wilcoxon (Mann-Whitney)</method>
          </analysis>
        </analysis_list>
      </outcome>
      <outcome>
        <type>Primary</type>
        <title>RNA Concentrations From Gastrointestinal Tissues</title>
        <description>We measured RNA concentrations in copies/1000cells for both drug groups</description>
        <time_frame>2 to 6 hours post dose</time_frame>
        <group_list>
          <group group_id="O1">
            <title>Group A</title>
            <description>Ten HIV-infected adults will be in Group A and take the HIV medication raltegravir in combination with tenofovir and emtricitabine as their provider-prescribed antiretroviral regimen.&#xD;
Raltegravir&#xD;
Colonoscopy with biopsy: This procedure is not standard of care for patients receiving combination antiretroviral therapy (cART), but is necessary to obtain tissue samples.</description>
          </group>
          <group group_id="O2">
            <title>Group B</title>
            <description>Ten HIV-infected adults will be in Group B and take the HIV medication dolutegravir in combination with tenofovir and emtricitabine as their provider-prescribed antiretroviral regimen.&#xD;
Dolutegravir&#xD;
Colonoscopy with biopsy: This procedure is not standard of care for patients receiving combination antiretroviral therapy (cART), but is necessary to obtain tissue samples.</description>
          </group>
        </group_list>
        <measure>
          <title>RNA Concentrations From Gastrointestinal Tissues</title>
          <description>We measured RNA concentrations in copies/1000cells for both drug groups</description>
          <units>copies/1000cells</units>
          <param>Median</param>
          <dispersion>Full Range</dispersion>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="10"/>
                <count group_id="O2" value="10"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="0.05" lower_limit="0.03" upper_limit="0.34"/>
                    <measurement group_id="O2" value="0.16" lower_limit="0.01" upper_limit="36.19"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </outcome>
      <outcome>
        <type>Primary</type>
        <title>Percentage of Total CD8+ T-cells With CCR5 Expression</title>
        <description>Local immunologic markers in gastrointestinal tract tissues</description>
        <time_frame>2 to 6 hours post dose</time_frame>
        <group_list>
          <group group_id="O1">
            <title>Group A</title>
            <description>Ten HIV-infected adults will be in Group A and take the HIV medication raltegravir in combination with tenofovir and emtricitabine as their provider-prescribed antiretroviral regimen.&#xD;
Raltegravir&#xD;
Colonoscopy with biopsy: This procedure is not standard of care for patients receiving combination antiretroviral therapy (cART), but is necessary to obtain tissue samples.</description>
          </group>
          <group group_id="O2">
            <title>Group B</title>
            <description>Ten HIV-infected adults will be in Group B and take the HIV medication dolutegravir in combination with tenofovir and emtricitabine as their provider-prescribed antiretroviral regimen.&#xD;
Dolutegravir&#xD;
Colonoscopy with biopsy: This procedure is not standard of care for patients receiving combination antiretroviral therapy (cART), but is necessary to obtain tissue samples.</description>
          </group>
        </group_list>
        <measure>
          <title>Percentage of Total CD8+ T-cells With CCR5 Expression</title>
          <description>Local immunologic markers in gastrointestinal tract tissues</description>
          <units>percentage of total cells</units>
          <param>Median</param>
          <dispersion>Full Range</dispersion>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="10"/>
                <count group_id="O2" value="10"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="0.15" lower_limit="0.07" upper_limit="0.52"/>
                    <measurement group_id="O2" value="0.64" lower_limit="0.24" upper_limit="1.60"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </outcome>
    </outcome_list>

    <reported_events>
      <time_frame>Adverse events were collected from the time of informed consent at the screening visit (up to 42 days prior to enrollment) through study completion (Up to 14 days after last sampling).</time_frame>
      <desc>Adverse events were assessed at all visits with a standardized IRB-approved questionnaire.</desc>
      <group_list>
        <group group_id="E1">
          <title>Group A</title>
          <description>Ten HIV-infected adults will be in Group A and take the HIV medication raltegravir in combination with tenofovir and emtricitabine as their provider-prescribed antiretroviral regimen.&#xD;
Raltegravir&#xD;
Colonoscopy with biopsy: This procedure is not standard of care for patients receiving combination antiretroviral therapy (cART), but is necessary to obtain tissue samples. All participants underwent a bowel prep with subsequent colonoscopy to obtain tissue samples.</description>
        </group>
        <group group_id="E2">
          <title>Group B</title>
          <description>Ten HIV-infected adults will be in Group B and take the HIV medication dolutegravir in combination with tenofovir and emtricitabine as their provider-prescribed antiretroviral regimen.&#xD;
Dolutegravir&#xD;
Colonoscopy with biopsy: This procedure is not standard of care for patients receiving combination antiretroviral therapy (cART), but is necessary to obtain tissue samples.All participants underwent a bowel prep with subsequent colonoscopy to obtain tissue samples.</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="10"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="10"/>
              </event>
              <event>
                <sub_title>Total, serious adverse events</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="10"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="10"/>
              </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="3" subjects_at_risk="10"/>
                <counts group_id="E2" subjects_affected="3" subjects_at_risk="10"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Blood and lymphatic system disorders</title>
            <event_list>
              <event>
                <sub_title>Thombophlebitis</sub_title>
                <description>Onset 26Apr15, resolution 15May15, treated with Clindamycin</description>
                <counts group_id="E1" events="0" subjects_affected="0" subjects_at_risk="10"/>
                <counts group_id="E2" events="1" subjects_affected="1" subjects_at_risk="10"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Gastrointestinal disorders</title>
            <event_list>
              <event>
                <sub_title>Anal Irritation</sub_title>
                <description>Onset and resolution 28Jan2015. Participant used aloe wipe on anus and symptoms resolved.</description>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="10"/>
                <counts group_id="E2" events="0" subjects_affected="0" subjects_at_risk="10"/>
              </event>
              <event>
                <sub_title>Abdominal gas cramps</sub_title>
                <description>Onset and resolution 06Jan2015. Patient ambulated to resolution of symptoms with one dose of Tylenol.</description>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="10"/>
                <counts group_id="E2" events="1" subjects_affected="1" subjects_at_risk="10"/>
              </event>
              <event>
                <sub_title>Diarrhea</sub_title>
                <description>Onset 13Dec14 and resolution 18Dec14. Resolved without treatment.</description>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="10"/>
                <counts group_id="E2" events="0" subjects_affected="0" subjects_at_risk="10"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Respiratory, thoracic and mediastinal disorders</title>
            <event_list>
              <event>
                <sub_title>Hypertension</sub_title>
                <description>Elevated reading of blood pressure were noted on study, beginning 04May2015. Participant referred to PCP for management.</description>
                <counts group_id="E1" events="0" subjects_affected="0" subjects_at_risk="10"/>
                <counts group_id="E2" events="1" subjects_affected="1" subjects_at_risk="10"/>
              </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>Dr. Angela Kashuba</name_or_title>
      <organization>University of North Carolina at Chapel Hill</organization>
      <phone>919 966-9998</phone>
      <email>akashuba@unc.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/NCT02218320
org study id: 14-1647
nct id: NCT02218320
lead sponsor: 
collaborator: 
has dmc: No
is fda regulated drug: Yes
is fda regulated device: No
is us export: No
This is a Phase IV, open label, observational study to compare the gastrointestinal tissue
      concentrations, inflammatory response, and viral replication of two integrase-inhibitors,
      raltegravir and dolutegravir, in HIV-infected volunteers who are virologically suppressed in
      blood plasma. The study will be comprised of 20 HIV-infected volunteers who will be enrolled
      equally into two groups. Group A will consist of 10 subjects receiving an antiretroviral
      regimen of tenofovir, emtricitabine, and raltegravir, and Group B will consist of 10 subjects
      receiving an antiretroviral regimen of tenofovir, emtricitabine, and dolutegravir.
      Participants will provide small pieces of tissue, or biopsies, which will be taken from three
      distinct locations of the large intestine during a colonoscopy procedure. These biopsies will
      be used to measure the amount of raltegravir or dolutegravir, HIV virus, and inflammatory
      markers present in the gastrointestinal tract.
Purpose: To compare virologic and immunologic responses to raltegravir and dolutegravir in
      the gastrointestinal tract of HIV-positive men and women

      Participants: Twenty HIV-infected volunteers will be enrolled equally into two groups. Group
      A will consist of subjects receiving an antiretroviral regimen of raltegravir, tenofovir, and
      emtricitabine and Group B will consist of subjects receiving an antiretroviral regimen of
      dolutegravir, tenofovir, and emtricitabine.

      Procedures (methods): This is a Phase IV, open label study to compare the gastrointestinal
      tissue concentrations, cytokine response, and viral replication in gut-associated lymphoid
      tissue of two integrase-inhibitors in HIV-infected volunteers who are virologically
      suppressed in blood plasma. Subjects will undergo an observed bowel preparation, followed by
      a colonoscopy in which tissue will be obtained by a board-certified gastroenterologist from
      the terminal ileum/ascending colon, splenic flexture, and rectum/sigmoid colon. Blood plasma
      will be collected immediately prior to collection of tissue samples.
observational model: Other
time perspective: Prospective
measure: Rectal Tissue Concentrations of Ralegravir and Dolutegravir
time frame: 2 to 6 hours post dose
measure: RNA Concentrations From Gastrointestinal Tissues
time frame: 2 to 6 hours post dose
description: We measured RNA concentrations in copies/1000cells for both drug groups
measure: Percentage of Total CD8+ T-cells With CCR5 Expression
time frame: 2 to 6 hours post dose
description: Local immunologic markers in gastrointestinal tract tissues
arm group label: Group A
description: Ten HIV-infected adults will be in Group A and take the HIV medication raltegravir in combination with tenofovir and emtricitabine as their provider-prescribed antiretroviral regimen.
arm group label: Group B
description: Ten HIV-infected adults will be in Group B and take the HIV medication dolutegravir in combination with tenofovir and emtricitabine as their provider-prescribed antiretroviral regimen.
intervention type: Drug
intervention name: Raltegravir
arm group label: Group A
other name: Isentress ®
intervention type: Drug
intervention name: Dolutegravir
arm group label: Group B
other name: Tivicay ®
intervention type: Procedure
intervention name: Colonoscopy with biopsy
description: This procedure is not standard of care for patients receiving combination antiretroviral therapy (cART), but is necessary to obtain tissue samples.
arm group label: Group A
arm group label: Group B
study pop: 
sampling method: Non-Probability Sample
criteria: 
gender: All
minimum age: 18 Years
maximum age: 65 Years
healthy volunteers: No
last name: Angela DM Kashuba, PharmD
role: Principal Investigator
affiliation: University of North Carolina, Chapel Hill
facility: 
country: United States
responsible party type: Sponsor
mesh term: Acquired Immunodeficiency Syndrome
mesh term: HIV Infections
mesh term: Raltegravir Potassium
mesh term: Dolutegravir
sharing ipd: No
participant flow: 
baseline: 
outcome list: 
reported events: 
certain agreements: 
point of contact: 