<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/NCT02258685</url>
  </required_header>
  <id_info>
    <org_study_id>14-1595</org_study_id>
    <nct_id>NCT02258685</nct_id>
  </id_info>
  <brief_title>Factors Mediating Gut Microbiota Dysbiosis and Metabolic Disease in HIV Patients.</brief_title>
  <official_title>Factors Mediating Gut Microbiota Dysbiosis and Metabolic Disease in HIV Patients.</official_title>
  <sponsors>
    <lead_sponsor>
      <agency>University of Colorado, Denver</agency>
      <agency_class>Other</agency_class>
    </lead_sponsor>
  </sponsors>
  <source>University of Colorado, Denver</source>
  <oversight_info>
    <has_dmc>No</has_dmc>
  </oversight_info>
  <brief_summary>
    <textblock>
      This study plans to learn more about immune responses in intestinal (gut) tissue in people&#xD;
      with human immunodeficiency virus (HIV) infection. This study will determine whether change&#xD;
      in the composition of gut bacteria in HIV infected individuals is related to a high&#xD;
      prevalence of chronic gut inflammation and metabolic disease. The investigators will also&#xD;
      investigate immune-modulatory properties of specific bacteria that correlate with disease&#xD;
      both by characterizing which functional genes are selected for in their genomes and by&#xD;
      stimulating immune cells isolated from blood and gut tissue with bacterial isolates. This&#xD;
      work will establish whether gain/loss of bacterial drivers/suppressors of information in the&#xD;
      gut contributes to metabolic disease in HIV-infected individuals.&#xD;
    </textblock>
  </brief_summary>
  <detailed_description>
    <textblock>
      This is a prospective cohort and cross-sectional case-control study. Study participation will&#xD;
      last up to 2 months and 93 participants will be enrolled. Participants will be evaluated for&#xD;
      lipodystrophy, asked to complete food &amp; gastrointestinal symptoms questionnaires and provide&#xD;
      stool samples. A subset of participants will be asked to have a flexible sigmoidoscopy&#xD;
      (mucosal biopsy).&#xD;
&#xD;
      Cohort A will consist of 93 participants:&#xD;
&#xD;
      Cohort A1: ART (Antiretroviral therapy) -treated HIV-infected individuals with lipodystrophy&#xD;
      (n=35) Cohort A2: ART-treated HIV-infected individuals without lipodystrophy (n=18) Cohort&#xD;
      A3: HIV-1 infected individuals naïve to ART (n=20) Cohort A4: HIV-1 seronegative individuals&#xD;
      who are at a high risk for infection (n=20)&#xD;
&#xD;
      Cohort B will be a selected subset of subjects from Cohort A:&#xD;
&#xD;
      Cohort B1: ART-treated HIV-infected individuals with HIV-associated dysbiosis (n=10) Cohort&#xD;
      B2: ART-treated HIV-infected individuals without HIV-associated dysbiosis (n=10)&#xD;
    </textblock>
  </detailed_description>
  <overall_status>Completed</overall_status>
  <start_date type="Actual">November 2014</start_date>
  <completion_date type="Actual">July 2019</completion_date>
  <primary_completion_date type="Actual">November 2018</primary_completion_date>
  <study_type>Observational</study_type>
  <has_expanded_access>No</has_expanded_access>
  <study_design_info>
    <observational_model>Cohort</observational_model>
    <time_perspective>Cross-Sectional</time_perspective>
  </study_design_info>
  <primary_outcome>
    <measure>Determine the gut microbiota composition using 16S ribosomal RNA (rRNA) sequencing of fecal samples</measure>
    <time_frame>2 months</time_frame>
    <description>Compare the gut microbiota composition of HIV-positive subjects with and without lipodystrophy and long-term ART, and HIV-negative controls with diet and metabolic and immune activation markers in blood.</description>
  </primary_outcome>
  <primary_outcome>
    <measure>Determine of gut microbiota composition using rectosigmoid biopsy tissue</measure>
    <time_frame>2 months</time_frame>
    <description>Compare the gut microbiota composition of HIV-positive ART-treated individuals by CD4+ populations and immune activation markers in gut-associated lymphoid tissues (GALT)</description>
  </primary_outcome>
  <number_of_groups>6</number_of_groups>
  <enrollment type="Actual">93</enrollment>
  <condition>HIV</condition>
  <condition>Lipodystrophy</condition>
  <arm_group>
    <arm_group_label>Cohort A1</arm_group_label>
    <description>ART-treated HIV-infected individuals with lipodystrophy</description>
  </arm_group>
  <arm_group>
    <arm_group_label>Cohort A2</arm_group_label>
    <description>ART-treated HIV-infected individuals without lipodystrophy</description>
  </arm_group>
  <arm_group>
    <arm_group_label>Cohort A3</arm_group_label>
    <description>HIV-1 infected individuals naïve to ART</description>
  </arm_group>
  <arm_group>
    <arm_group_label>Cohort A4</arm_group_label>
    <description>HIV-1 seronegative individuals who are at a high risk for infection</description>
  </arm_group>
  <arm_group>
    <arm_group_label>Cohort B1</arm_group_label>
    <description>A subset of subjects from Cohort A: ART-treated HIV-infected individuals with HIV-associated dysbiosis</description>
  </arm_group>
  <arm_group>
    <arm_group_label>Cohort B2</arm_group_label>
    <description>A subset of subjects from Cohort A: ART-treated HIV-infected individuals without HIV-associated dysbiosis</description>
  </arm_group>
  <biospec_retention>Samples Without DNA</biospec_retention>
  <biospec_descr>
    <textblock>
      Blood and rectosigmoid biopsy tissue will be collected.&#xD;
    </textblock>
  </biospec_descr>
  <eligibility>
    <study_pop>
      <textblock>
        HIV positive and HIV negative subjects (with and without lipodystrophy) between 18 and 65&#xD;
        years old.&#xD;
      </textblock>
    </study_pop>
    <sampling_method>Non-Probability Sample</sampling_method>
    <criteria>
      <textblock>
        Inclusion Criteria:&#xD;
&#xD;
          -  Men and women; 18 years to 65 years (All Cohorts)&#xD;
&#xD;
          -  Subjects with chronic HIV-1 Infection defined as a positive ELISA confirmed by a&#xD;
             positive Western Blot or plasma HIV-1 RNA level &gt;1,000 copies/mL at any time in the&#xD;
             past. (Cohorts A1, A2 &amp; A3)&#xD;
&#xD;
          -  HIV-1 seronegative (Cohort A4)&#xD;
&#xD;
          -  Either with or without lipodystrophy (to be assessed at Visit 1)&#xD;
&#xD;
          -  Body mass index (BMI) between 21-29 mg/kg2 and weight stable for at least 3 months&#xD;
             (All Cohorts)&#xD;
&#xD;
          -  Antiretroviral therapy (ART) naïve (Cohort A3): &lt;10 days of ART treatment at any time&#xD;
             prior to Visit 1 or previously on ART but off treatment for the previous 6 months&#xD;
             prior to Visit 1&#xD;
&#xD;
          -  Long-term ART (Cohort A1 &amp; A2): Must be on same antiretroviral treatment and have a&#xD;
             plasma HIV-1 RNA &lt;25 copies/mL for 3-6 months prior to Visit 1.Liver function tests&#xD;
             not greater than 2x normal, normal kidney and thyroid function. Fasting glucose must&#xD;
             be &lt;110 mg/dl&#xD;
&#xD;
          -  Liver function tests not greater than 2x normal, normal kidney and thyroid function.&#xD;
             Fasting glucose must be &lt;110 mg/dl&#xD;
&#xD;
          -  ART-treated individuals whose microbiota resembles those with untreated HIV infection&#xD;
             and ART-treated individuals whose microbiota resembles the HIV-negative control cohort&#xD;
             (equal numbers with and without lipodystrophy).(Cohort B; a subset of Cohort A)&#xD;
&#xD;
        Exclusion Criteria:&#xD;
&#xD;
          -  Gastrointestinal disease such as inflammatory bowel disease, Clostridium difficile&#xD;
             colitis or celiac sprue.&#xD;
&#xD;
          -  history of bowel resection, bleeding disorder, history of hyperglycemia, treated with&#xD;
             high-dose glucocorticoid therapy or alpha-interferon in past year Current use of&#xD;
             anticoagulant therapy&#xD;
&#xD;
          -  Daily use of aspirin or nonsteroidal antiinflammatory drugs (NSAIDs) with inability to&#xD;
             withhold drug for 7 days before and after a rectosigmoid biopsy procedure.&#xD;
&#xD;
          -  Used antibiotics within the prior three months&#xD;
&#xD;
          -  Pregnancy&#xD;
&#xD;
          -  Current use of proton pump inhibitors and H2-blockers&#xD;
&#xD;
          -  Active opportunistic or other chronic infection, such as hepatitis B or C or an active&#xD;
             malignancy&#xD;
&#xD;
          -  Patient inability to participate in the study, such as inability to undergo&#xD;
             venipuncture, completion of questionnaire or mucosal biopsy (if selected) procedures&#xD;
             that form part of the inclusion/exclusion criteria or part of the outcome measure.&#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>Catherine Lozupone, PhD</last_name>
    <role>Principal Investigator</role>
    <affiliation>University of Colorado, Denver</affiliation>
  </overall_official>
  <location>
    <facility>
      <name>University of Colorado Denver</name>
      <address>
        <city>Aurora</city>
        <state>Colorado</state>
        <zip>80045</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location_countries>
    <country>United States</country>
  </location_countries>
  <verification_date>December 2019</verification_date>
  <study_first_submitted>October 1, 2014</study_first_submitted>
  <study_first_submitted_qc>October 2, 2014</study_first_submitted_qc>
  <study_first_posted type="Estimate">October 7, 2014</study_first_posted>
  <last_update_submitted>December 16, 2019</last_update_submitted>
  <last_update_submitted_qc>December 16, 2019</last_update_submitted_qc>
  <last_update_posted type="Actual">December 18, 2019</last_update_posted>
  <responsible_party>
    <responsible_party_type>Sponsor</responsible_party_type>
  </responsible_party>
  <keyword>Gut microbiota composition</keyword>
  <condition_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Lipodystrophy</mesh_term>
    <mesh_term>Metabolic Diseases</mesh_term>
    <mesh_term>Dysbiosis</mesh_term>
  </condition_browse>
  <!-- Results have not yet been posted for this study                                          -->
</clinical_study>


download date: ClinicalTrials.gov processed this data on September 20, 2023
link text: Link to the current ClinicalTrials.gov record.
url: https://clinicaltrials.gov/ct2/show/NCT02258685
org study id: 14-1595
nct id: NCT02258685
lead sponsor: 
has dmc: No
This study plans to learn more about immune responses in intestinal (gut) tissue in people
      with human immunodeficiency virus (HIV) infection. This study will determine whether change
      in the composition of gut bacteria in HIV infected individuals is related to a high
      prevalence of chronic gut inflammation and metabolic disease. The investigators will also
      investigate immune-modulatory properties of specific bacteria that correlate with disease
      both by characterizing which functional genes are selected for in their genomes and by
      stimulating immune cells isolated from blood and gut tissue with bacterial isolates. This
      work will establish whether gain/loss of bacterial drivers/suppressors of information in the
      gut contributes to metabolic disease in HIV-infected individuals.
This is a prospective cohort and cross-sectional case-control study. Study participation will
      last up to 2 months and 93 participants will be enrolled. Participants will be evaluated for
      lipodystrophy, asked to complete food & gastrointestinal symptoms questionnaires and provide
      stool samples. A subset of participants will be asked to have a flexible sigmoidoscopy
      (mucosal biopsy).

      Cohort A will consist of 93 participants:

      Cohort A1: ART (Antiretroviral therapy) -treated HIV-infected individuals with lipodystrophy
      (n=35) Cohort A2: ART-treated HIV-infected individuals without lipodystrophy (n=18) Cohort
      A3: HIV-1 infected individuals naïve to ART (n=20) Cohort A4: HIV-1 seronegative individuals
      who are at a high risk for infection (n=20)

      Cohort B will be a selected subset of subjects from Cohort A:

      Cohort B1: ART-treated HIV-infected individuals with HIV-associated dysbiosis (n=10) Cohort
      B2: ART-treated HIV-infected individuals without HIV-associated dysbiosis (n=10)
observational model: Cohort
time perspective: Cross-Sectional
measure: Determine the gut microbiota composition using 16S ribosomal RNA (rRNA) sequencing of fecal samples
time frame: 2 months
description: Compare the gut microbiota composition of HIV-positive subjects with and without lipodystrophy and long-term ART, and HIV-negative controls with diet and metabolic and immune activation markers in blood.
measure: Determine of gut microbiota composition using rectosigmoid biopsy tissue
time frame: 2 months
description: Compare the gut microbiota composition of HIV-positive ART-treated individuals by CD4+ populations and immune activation markers in gut-associated lymphoid tissues (GALT)
arm group label: Cohort A1
description: ART-treated HIV-infected individuals with lipodystrophy
arm group label: Cohort A2
description: ART-treated HIV-infected individuals without lipodystrophy
arm group label: Cohort A3
description: HIV-1 infected individuals naïve to ART
arm group label: Cohort A4
description: HIV-1 seronegative individuals who are at a high risk for infection
arm group label: Cohort B1
description: A subset of subjects from Cohort A: ART-treated HIV-infected individuals with HIV-associated dysbiosis
arm group label: Cohort B2
description: A subset of subjects from Cohort A: ART-treated HIV-infected individuals without HIV-associated dysbiosis
Blood and rectosigmoid biopsy tissue will be collected.
study pop: 
sampling method: Non-Probability Sample
criteria: 
gender: All
minimum age: 18 Years
maximum age: 65 Years
healthy volunteers: Accepts Healthy Volunteers
last name: Catherine Lozupone, PhD
role: Principal Investigator
affiliation: University of Colorado, Denver
facility: 
country: United States
responsible party type: Sponsor
mesh term: Lipodystrophy
mesh term: Metabolic Diseases
mesh term: Dysbiosis