<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/NCT02256592</url>
  </required_header>
  <id_info>
    <org_study_id>13-12675</org_study_id>
    <nct_id>NCT02256592</nct_id>
  </id_info>
  <brief_title>Fecal Microbiota Transplantation in HIV</brief_title>
  <acronym>FMT-HIV</acronym>
  <official_title>Reconstitution of the Gut Microbiome to Reduce HIV-Associated Inflammation</official_title>
  <sponsors>
    <lead_sponsor>
      <agency>University of California, San Francisco</agency>
      <agency_class>Other</agency_class>
    </lead_sponsor>
    <collaborator>
      <agency>American College of Gastroenterology</agency>
      <agency_class>Other</agency_class>
    </collaborator>
    <collaborator>
      <agency>National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK)</agency>
      <agency_class>NIH</agency_class>
    </collaborator>
  </sponsors>
  <source>University of California, San Francisco</source>
  <oversight_info>
    <has_dmc>No</has_dmc>
  </oversight_info>
  <brief_summary>
    <textblock>
      Even in individuals treated for HIV, chronic immune activation persists and is associated&#xD;
      with increased cardiovascular disease, liver disease, and mortality. HIV-infected individuals&#xD;
      have imbalances in the community of intestinal microbes which is thought to contribute to&#xD;
      increased and persistent inflammation. The purpose of this study is to examine the safety and&#xD;
      durability of fecal microbiota transplant (FMT), the transfer of the bacterial community in&#xD;
      stool from a healthy donor, in HIV+ individuals on anti-retroviral therapy. The study will&#xD;
      also measure the effects of FMT on immune activation and inflammatory biomarkers in&#xD;
      anti-retroviral treated HIV+ individuals.&#xD;
    </textblock>
  </brief_summary>
  <detailed_description>
    <textblock>
      Despite antiretroviral therapy (ART), chronic immune activation persists and is a major&#xD;
      driver of HIV disease progression and mortality among HIV-infected individuals. Importantly,&#xD;
      persistent inflammation is strongly associated with increased cardiovascular events,&#xD;
      accelerated liver disease, impaired immunologic recovery (e.g. low CD4 count, low CD4 to CD8&#xD;
      ratio), and mortality. Therefore, addressing persistent inflammation remains a major goal to&#xD;
      restoring health in HIV-infected individuals.&#xD;
&#xD;
      Novel therapeutic strategies to decrease immune activation in treated HIV infection are&#xD;
      needed. Marked disruption of the gut microbial composition, or dysbiosis, is characteristic&#xD;
      of HIV-infected individuals and persists despite long-term ART. Recent studies demonstrate&#xD;
      that the relative degree of gut microbiome disruption positively correlates with inflammatory&#xD;
      markers (IL-6, kynurenine to tryptophan ratio). Microbial dysbiosis and its inflammatory&#xD;
      consequences may be an attractive target for interventions to decrease immune activation in&#xD;
      HIV+ individuals.&#xD;
&#xD;
      Fecal microbiome transplantation (FMT) has proven durable and successful as a therapeutic&#xD;
      strategy against gut dysbiosis, such as in the treatment of recurrent Clostridium difficile&#xD;
      infection, by restructuring the composition of the gut microbiome to resemble that of the&#xD;
      healthy donor. FMT has an established record of safety with limited adverse effects, even in&#xD;
      the context of immunocompromised and HIV-infected subjects. Donor selection and screening&#xD;
      will be conducted by OpenBiome.&#xD;
&#xD;
      The objective of this phase I clinical trial is to establish the safety and durability of FMT&#xD;
      in HIV+ individuals. The microbiome of recipients will be analyzed up to 8 weeks post FMT for&#xD;
      evidence of engraftment from the donor microbiome. We will further examine the effect of FMT&#xD;
      on markers of immune activation and inflammation in ART treated HIV-infected individuals.&#xD;
    </textblock>
  </detailed_description>
  <overall_status>Completed</overall_status>
  <start_date>October 2014</start_date>
  <completion_date type="Actual">March 2017</completion_date>
  <primary_completion_date type="Actual">March 2017</primary_completion_date>
  <phase>Phase 1</phase>
  <study_type>Interventional</study_type>
  <has_expanded_access>No</has_expanded_access>
  <study_design_info>
    <allocation>N/A</allocation>
    <intervention_model>Single Group Assignment</intervention_model>
    <primary_purpose>Treatment</primary_purpose>
    <masking>None (Open Label)</masking>
  </study_design_info>
  <primary_outcome>
    <measure>Safety of FMT in HIV-infected individuals on suppressive ART.</measure>
    <time_frame>0-24 weeks post-FMT</time_frame>
    <description>Determine the proportion of individuals with AE/SAE. Record AE/SAE during FMT and post-FMT and determine if related to study procedure and graded for severity. Study stoppage criteria includes any serious AE that is at least possibly related to study treatment or any serious infection (e.g., bacteremia) in a sterile body site with an organism potentially acquired from the FMT product.</description>
  </primary_outcome>
  <primary_outcome>
    <measure>Engraftment of donor microbiome in HIV-infected individuals on suppressive ART.</measure>
    <time_frame>8 weeks post-FMT</time_frame>
    <description>The weighted Canberra distance, which calculates community similarity based on shared OTU membership irrespective of phylogenetic relatedness, and weighted UniFrac which considers phylogenetic similarity of microbial communities, will both be applied to compare the microbiome of FMT recipients over time to those of the donor infusion sample.</description>
  </primary_outcome>
  <secondary_outcome>
    <measure>Plasma will be analyzed for changes in levels of markers of inflammation (e.g. IL-6, sCD14, kynurenine to tryptophan ratio) and CD4 and CD8 T cell activation</measure>
    <time_frame>8 weeks post-FMT</time_frame>
    <description>pre-FMT and 8 weeks post-FMT.</description>
  </secondary_outcome>
  <number_of_arms>1</number_of_arms>
  <enrollment type="Actual">18</enrollment>
  <condition>HIV</condition>
  <arm_group>
    <arm_group_label>Fecal microbiota transplant (FMT)</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>Donor fecal suspension will be delivered during colonoscopy to HIV+ individuals.</description>
  </arm_group>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>Fecal Microbiota</intervention_name>
    <description>300 mL of fecal suspension from a healthy donor will be delivered during colonoscopy</description>
    <arm_group_label>Fecal microbiota transplant (FMT)</arm_group_label>
    <other_name>stool transplant</other_name>
  </intervention>
  <eligibility>
    <criteria>
      <textblock>
        Inclusion Criteria:&#xD;
&#xD;
          1. HIV infected men and women 18-75 years of age.&#xD;
&#xD;
          2. On continuous anti-retroviral therapy for at least one year.&#xD;
&#xD;
          3. Undetectable viral load for at least one year.&#xD;
&#xD;
          4. Written informed consent obtained from the subject and ability of the subject to&#xD;
             comply with the requirements of the study.&#xD;
&#xD;
        Exclusion Criteria:&#xD;
&#xD;
          1. CD4 T cell count less than 200 cells/mL.&#xD;
&#xD;
          2. Recent antibiotic use in the last 3 months.&#xD;
&#xD;
          3. Pregnant, breastfeeding, or unwilling to practice birth control during participation&#xD;
             in the study.&#xD;
&#xD;
          4. Presence of a condition or abnormality that in the opinion of the Investigator would&#xD;
             compromise the safety of the patient or the quality of the data.&#xD;
&#xD;
          5. Active GI symptoms: inflammatory bowel disease, abdominal pain, hematochezia, or other&#xD;
             symptoms requiring medical evaluation and intervention.&#xD;
&#xD;
          6. Recent hospitalization or acute medical condition within preceding three months.&#xD;
&#xD;
          7. Severe comorbidities: cirrhosis, coagulopathy, heart failure, renal failure, and&#xD;
             respiratory failure.&#xD;
&#xD;
          8. Testing positive for any of the stool screening test: Clostridium difficile toxin by&#xD;
             PCR, routine bacterial culture for enteric pathogens (E coli, Salmonella, Shigella,&#xD;
             Yersinia, Campylobacter), culture for Vibrio, fecal Giardia antigen, fecal&#xD;
             Cryptosporidium antigen, acid-fast stain for Cyclospora and Isospora, ova and&#xD;
             parasites, stool for Rotavirus via EIA.&#xD;
&#xD;
          9. History of anaphylaxis.&#xD;
&#xD;
         10. Major immunosuppressive medications (e.g., calcineurin inhibitors, exogenous&#xD;
             glucocorticoids, biological agents, etc.) or systemic antineoplastic agents.&#xD;
      </textblock>
    </criteria>
    <gender>All</gender>
    <minimum_age>18 Years</minimum_age>
    <maximum_age>75 Years</maximum_age>
    <healthy_volunteers>No</healthy_volunteers>
  </eligibility>
  <overall_official>
    <last_name>Ma Somsouk, MD</last_name>
    <role>Principal Investigator</role>
    <affiliation>University of California, San Francisco</affiliation>
  </overall_official>
  <location>
    <facility>
      <name>University of California, San Francisco-San Francisco General Hospital</name>
      <address>
        <city>San Francisco</city>
        <state>California</state>
        <zip>94110</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location_countries>
    <country>United States</country>
  </location_countries>
  <reference>
    <citation>Duprez DA, Neuhaus J, Kuller LH, Tracy R, Belloso W, De Wit S, Drummond F, Lane HC, Ledergerber B, Lundgren J, Nixon D, Paton NI, Prineas RJ, Neaton JD; INSIGHT SMART Study Group. Inflammation, coagulation and cardiovascular disease in HIV-infected individuals. PLoS One. 2012;7(9):e44454. doi: 10.1371/journal.pone.0044454. Epub 2012 Sep 10.</citation>
    <PMID>22970224</PMID>
  </reference>
  <reference>
    <citation>Vujkovic-Cvijin I, Dunham RM, Iwai S, Maher MC, Albright RG, Broadhurst MJ, Hernandez RD, Lederman MM, Huang Y, Somsouk M, Deeks SG, Hunt PW, Lynch SV, McCune JM. Dysbiosis of the gut microbiota is associated with HIV disease progression and tryptophan catabolism. Sci Transl Med. 2013 Jul 10;5(193):193ra91. doi: 10.1126/scitranslmed.3006438. Erratum In: Sci Transl Med. 2017 Nov 8;9(415):</citation>
    <PMID>23843452</PMID>
  </reference>
  <verification_date>May 2017</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 3, 2014</study_first_posted>
  <last_update_submitted>May 2, 2017</last_update_submitted>
  <last_update_submitted_qc>May 2, 2017</last_update_submitted_qc>
  <last_update_posted type="Actual">May 4, 2017</last_update_posted>
  <responsible_party>
    <responsible_party_type>Principal Investigator</responsible_party_type>
    <investigator_affiliation>University of California, San Francisco</investigator_affiliation>
    <investigator_full_name>Ma Somsouk, MD, MAS</investigator_full_name>
    <investigator_title>Associate Professor</investigator_title>
  </responsible_party>
  <keyword>inflammation</keyword>
  <keyword>microbiome</keyword>
  <keyword>immune activation</keyword>
  <keyword>fecal microbiota transplantation</keyword>
  <keyword>dysbiosis</keyword>
  <!-- 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/NCT02256592
org study id: 13-12675
nct id: NCT02256592
lead sponsor: 
collaborator: 
collaborator: 
has dmc: No
Even in individuals treated for HIV, chronic immune activation persists and is associated
      with increased cardiovascular disease, liver disease, and mortality. HIV-infected individuals
      have imbalances in the community of intestinal microbes which is thought to contribute to
      increased and persistent inflammation. The purpose of this study is to examine the safety and
      durability of fecal microbiota transplant (FMT), the transfer of the bacterial community in
      stool from a healthy donor, in HIV+ individuals on anti-retroviral therapy. The study will
      also measure the effects of FMT on immune activation and inflammatory biomarkers in
      anti-retroviral treated HIV+ individuals.
Despite antiretroviral therapy (ART), chronic immune activation persists and is a major
      driver of HIV disease progression and mortality among HIV-infected individuals. Importantly,
      persistent inflammation is strongly associated with increased cardiovascular events,
      accelerated liver disease, impaired immunologic recovery (e.g. low CD4 count, low CD4 to CD8
      ratio), and mortality. Therefore, addressing persistent inflammation remains a major goal to
      restoring health in HIV-infected individuals.

      Novel therapeutic strategies to decrease immune activation in treated HIV infection are
      needed. Marked disruption of the gut microbial composition, or dysbiosis, is characteristic
      of HIV-infected individuals and persists despite long-term ART. Recent studies demonstrate
      that the relative degree of gut microbiome disruption positively correlates with inflammatory
      markers (IL-6, kynurenine to tryptophan ratio). Microbial dysbiosis and its inflammatory
      consequences may be an attractive target for interventions to decrease immune activation in
      HIV+ individuals.

      Fecal microbiome transplantation (FMT) has proven durable and successful as a therapeutic
      strategy against gut dysbiosis, such as in the treatment of recurrent Clostridium difficile
      infection, by restructuring the composition of the gut microbiome to resemble that of the
      healthy donor. FMT has an established record of safety with limited adverse effects, even in
      the context of immunocompromised and HIV-infected subjects. Donor selection and screening
      will be conducted by OpenBiome.

      The objective of this phase I clinical trial is to establish the safety and durability of FMT
      in HIV+ individuals. The microbiome of recipients will be analyzed up to 8 weeks post FMT for
      evidence of engraftment from the donor microbiome. We will further examine the effect of FMT
      on markers of immune activation and inflammation in ART treated HIV-infected individuals.
allocation: N/A
intervention model: Single Group Assignment
primary purpose: Treatment
masking: None (Open Label)
measure: Safety of FMT in HIV-infected individuals on suppressive ART.
time frame: 0-24 weeks post-FMT
description: Determine the proportion of individuals with AE/SAE. Record AE/SAE during FMT and post-FMT and determine if related to study procedure and graded for severity. Study stoppage criteria includes any serious AE that is at least possibly related to study treatment or any serious infection (e.g., bacteremia) in a sterile body site with an organism potentially acquired from the FMT product.
measure: Engraftment of donor microbiome in HIV-infected individuals on suppressive ART.
time frame: 8 weeks post-FMT
description: The weighted Canberra distance, which calculates community similarity based on shared OTU membership irrespective of phylogenetic relatedness, and weighted UniFrac which considers phylogenetic similarity of microbial communities, will both be applied to compare the microbiome of FMT recipients over time to those of the donor infusion sample.
measure: Plasma will be analyzed for changes in levels of markers of inflammation (e.g. IL-6, sCD14, kynurenine to tryptophan ratio) and CD4 and CD8 T cell activation
time frame: 8 weeks post-FMT
description: pre-FMT and 8 weeks post-FMT.
arm group label: Fecal microbiota transplant (FMT)
arm group type: Experimental
description: Donor fecal suspension will be delivered during colonoscopy to HIV+ individuals.
intervention type: Drug
intervention name: Fecal Microbiota
description: 300 mL of fecal suspension from a healthy donor will be delivered during colonoscopy
arm group label: Fecal microbiota transplant (FMT)
other name: stool transplant
criteria: 
gender: All
minimum age: 18 Years
maximum age: 75 Years
healthy volunteers: No
last name: Ma Somsouk, MD
role: Principal Investigator
affiliation: University of California, San Francisco
facility: 
country: United States
citation: Duprez DA, Neuhaus J, Kuller LH, Tracy R, Belloso W, De Wit S, Drummond F, Lane HC, Ledergerber B, Lundgren J, Nixon D, Paton NI, Prineas RJ, Neaton JD; INSIGHT SMART Study Group. Inflammation, coagulation and cardiovascular disease in HIV-infected individuals. PLoS One. 2012;7(9):e44454. doi: 10.1371/journal.pone.0044454. Epub 2012 Sep 10.
PMID: 22970224
citation: Vujkovic-Cvijin I, Dunham RM, Iwai S, Maher MC, Albright RG, Broadhurst MJ, Hernandez RD, Lederman MM, Huang Y, Somsouk M, Deeks SG, Hunt PW, Lynch SV, McCune JM. Dysbiosis of the gut microbiota is associated with HIV disease progression and tryptophan catabolism. Sci Transl Med. 2013 Jul 10;5(193):193ra91. doi: 10.1126/scitranslmed.3006438. Erratum In: Sci Transl Med. 2017 Nov 8;9(415):
PMID: 23843452
responsible party type: Principal Investigator
investigator affiliation: University of California, San Francisco
investigator full name: Ma Somsouk, MD, MAS
investigator title: Associate Professor