<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/NCT01670968</url>
  </required_header>
  <id_info>
    <org_study_id>HIV RCTS</org_study_id>
    <nct_id>NCT01670968</nct_id>
  </id_info>
  <brief_title>HIV Reverse Cholesterol Transport Study</brief_title>
  <acronym>HIV RCTS</acronym>
  <official_title>The Effect of Antiretroviral Therapy and HIV on Reverse Cholesterol Transport in Blood( HIV Reverse Cholesterol Transport Study- HIV RCTS)</official_title>
  <sponsors>
    <lead_sponsor>
      <agency>University College Dublin</agency>
      <agency_class>Other</agency_class>
    </lead_sponsor>
    <collaborator>
      <agency>Chelsea and Westminster NHS Foundation Trust</agency>
      <agency_class>Other</agency_class>
    </collaborator>
  </sponsors>
  <source>University College Dublin</source>
  <oversight_info>
    <has_dmc>No</has_dmc>
  </oversight_info>
  <brief_summary>
    <textblock>
      Primary Objective:&#xD;
&#xD;
      To examine changes in expression of genes [particularly ABCA1 and SREBP2] involved in reverse&#xD;
      cholesterol transport (RCT) in monocytes from HIV-infected subjects starting antiretroviral&#xD;
      therapy and the different effect of NNRTI and PI based regimens&#xD;
&#xD;
      Secondary Objective:&#xD;
&#xD;
      To examine changes in monocyte intracellular cholesterol content in HIV-infected subjects&#xD;
      starting antiretroviral therapy and the different effect of NNRTI and PI based regimens&#xD;
    </textblock>
  </brief_summary>
  <detailed_description>
    <textblock>
      HIV infection is associated with low HDL-cholesterol, an independent risk-factor for&#xD;
      cardiovascular disease (CVD). NNRTI-based HAART increases HDL-c, with nevirapine shown to&#xD;
      increase production of its major apolipoprotein ApoA-I. In contrast, initiation of PI-based&#xD;
      HAART leads to persistently low HDL-c despite a reduction in HIV RNA and immunologic&#xD;
      recovery.&#xD;
&#xD;
      HDL-c is formed through reverse cholesterol transport (RCT), the process where cholesterol is&#xD;
      transferred from intracellular pools to circulating lipoproteins which are then eliminated by&#xD;
      the liver. Accumulation of intracellular cholesterol in cells such as macrophages and their&#xD;
      precursor (circulating monocytes) has been implicated in atherogenesis.&#xD;
&#xD;
      In vitro data suggests the HIV protein Nef directly interferes with cellular proteins&#xD;
      involved in RCT such as ATP-binding cassette transporter A1 (ABCA1) in monocyte-derived&#xD;
      macrophages. ABCA1 expression is controlled by peroxisome proliferator-activated receptor&#xD;
      gamma (PPARG) and the intracellular cholesterol sensor sterol regulatory element binding&#xD;
      protein 2 (SREBP2). In adipose tissue it is known that PI treatment downregulates SREBP and&#xD;
      PPARG expression.&#xD;
&#xD;
      Preliminary work in the investigators lab has reproduced these findings in monocytes in&#xD;
      untreated HIV infection in vivo and demonstrated relationships between gene expression for&#xD;
      ABCA1, SREBP2, monocyte intracellular cholesterol and circulating lipoproteins. These early&#xD;
      data suggest that defects in RCT determine intracellular cholesterol levels in HIV-infected&#xD;
      subjects whereas increased LDL-c is a greater determinant of intracellular cholesterol in HIV&#xD;
      negative subjects. This suggests a potentially pivotal role for RCT abnormalities in low&#xD;
      HDL-c, increased intracellular cholesterol and atherogenesis in HIV infection.&#xD;
&#xD;
      The investigator's aim to examine the impact of initiation of ART with either PI or NNRTI on&#xD;
      RCT in circulating monocytes in vivo and how this impact correlates with changes in amount&#xD;
      and size of circulating HDL-c.&#xD;
    </textblock>
  </detailed_description>
  <overall_status>Unknown status</overall_status>
  <last_known_status>Recruiting</last_known_status>
  <start_date>September 2009</start_date>
  <completion_date type="Anticipated">June 2020</completion_date>
  <primary_completion_date type="Anticipated">May 2020</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>Prospective</time_perspective>
  </study_design_info>
  <primary_outcome>
    <measure>Change in ABCA1 mRNA expression in monocytes</measure>
    <time_frame>June 2013</time_frame>
  </primary_outcome>
  <enrollment type="Anticipated">100</enrollment>
  <condition>HIV</condition>
  <condition>Dyslipidemia</condition>
  <eligibility>
    <study_pop>
      <textblock>
        Individuals starting antiretroviral therapy at the Mater Misericordiae University Hospital,&#xD;
        Dublin, and Chelsea and Westminister Hospital, London&#xD;
      </textblock>
    </study_pop>
    <sampling_method>Probability Sample</sampling_method>
    <criteria>
      <textblock>
        Inclusion Criteria:&#xD;
&#xD;
          -  &gt; 18 years old&#xD;
&#xD;
          -  HIV-infected&#xD;
&#xD;
          -  Not currently on antiretroviral therapy (&gt;6/12), but about to start&#xD;
&#xD;
        Exclusion Criteria:&#xD;
&#xD;
          -  On lipid lowering medication (statin / fibrate / niacin)&#xD;
&#xD;
          -  HCV Ab+&#xD;
      </textblock>
    </criteria>
    <gender>All</gender>
    <minimum_age>18 Years</minimum_age>
    <maximum_age>N/A</maximum_age>
    <healthy_volunteers>No</healthy_volunteers>
  </eligibility>
  <overall_official>
    <last_name>Patrick WG Mallon, FRACP FRCPI PhD</last_name>
    <role>Principal Investigator</role>
    <affiliation>HIV Molecular Research Group, UCD School of Medicine and Medical Sciences. Department of Infectious Diseases, Mater Misericordiae University Hospital and Mater Private Hospital</affiliation>
  </overall_official>
  <overall_contact>
    <last_name>Patrick WG Mallon, MB BCh FRACP FRCPI PhD</last_name>
    <phone>+353 716 6311</phone>
    <email>paddy.mallon@ucd.ie</email>
  </overall_contact>
  <location>
    <facility>
      <name>Chelsea &amp; Westminster Hospital</name>
      <address>
        <city>London</city>
        <zip>SW10 9NH</zip>
        <country>United Kingdom</country>
      </address>
    </facility>
    <status>Recruiting</status>
    <contact>
      <last_name>Anton Pozniak</last_name>
      <phone>+44 20 8746 8000</phone>
      <email>anton.pozniak@chelwest.nhs.uk</email>
    </contact>
    <contact_backup>
      <last_name>Graeme Moyle</last_name>
      <phone>+44 20 8746 8000</phone>
      <email>gm@moyleg.demon.co.uk</email>
    </contact_backup>
    <investigator>
      <last_name>Anton Pozniak</last_name>
      <role>Principal Investigator</role>
    </investigator>
    <investigator>
      <last_name>Graeme Moyle</last_name>
      <role>Sub-Investigator</role>
    </investigator>
  </location>
  <location_countries>
    <country>United Kingdom</country>
  </location_countries>
  <verification_date>March 2020</verification_date>
  <study_first_submitted>August 18, 2012</study_first_submitted>
  <study_first_submitted_qc>August 22, 2012</study_first_submitted_qc>
  <study_first_posted type="Estimate">August 23, 2012</study_first_posted>
  <last_update_submitted>March 24, 2020</last_update_submitted>
  <last_update_submitted_qc>March 24, 2020</last_update_submitted_qc>
  <last_update_posted type="Actual">March 25, 2020</last_update_posted>
  <responsible_party>
    <responsible_party_type>Principal Investigator</responsible_party_type>
    <investigator_affiliation>University College Dublin</investigator_affiliation>
    <investigator_full_name>Patrick Mallon</investigator_full_name>
    <investigator_title>Associate Dean for Research and Innovation UCD School of Medicine and Medical Sciences, Consultant Infectious Diseases Physician</investigator_title>
  </responsible_party>
  <condition_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Dyslipidemias</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/NCT01670968
org study id: HIV RCTS
nct id: NCT01670968
lead sponsor: 
collaborator: 
has dmc: No
Primary Objective:

      To examine changes in expression of genes [particularly ABCA1 and SREBP2] involved in reverse
      cholesterol transport (RCT) in monocytes from HIV-infected subjects starting antiretroviral
      therapy and the different effect of NNRTI and PI based regimens

      Secondary Objective:

      To examine changes in monocyte intracellular cholesterol content in HIV-infected subjects
      starting antiretroviral therapy and the different effect of NNRTI and PI based regimens
HIV infection is associated with low HDL-cholesterol, an independent risk-factor for
      cardiovascular disease (CVD). NNRTI-based HAART increases HDL-c, with nevirapine shown to
      increase production of its major apolipoprotein ApoA-I. In contrast, initiation of PI-based
      HAART leads to persistently low HDL-c despite a reduction in HIV RNA and immunologic
      recovery.

      HDL-c is formed through reverse cholesterol transport (RCT), the process where cholesterol is
      transferred from intracellular pools to circulating lipoproteins which are then eliminated by
      the liver. Accumulation of intracellular cholesterol in cells such as macrophages and their
      precursor (circulating monocytes) has been implicated in atherogenesis.

      In vitro data suggests the HIV protein Nef directly interferes with cellular proteins
      involved in RCT such as ATP-binding cassette transporter A1 (ABCA1) in monocyte-derived
      macrophages. ABCA1 expression is controlled by peroxisome proliferator-activated receptor
      gamma (PPARG) and the intracellular cholesterol sensor sterol regulatory element binding
      protein 2 (SREBP2). In adipose tissue it is known that PI treatment downregulates SREBP and
      PPARG expression.

      Preliminary work in the investigators lab has reproduced these findings in monocytes in
      untreated HIV infection in vivo and demonstrated relationships between gene expression for
      ABCA1, SREBP2, monocyte intracellular cholesterol and circulating lipoproteins. These early
      data suggest that defects in RCT determine intracellular cholesterol levels in HIV-infected
      subjects whereas increased LDL-c is a greater determinant of intracellular cholesterol in HIV
      negative subjects. This suggests a potentially pivotal role for RCT abnormalities in low
      HDL-c, increased intracellular cholesterol and atherogenesis in HIV infection.

      The investigator's aim to examine the impact of initiation of ART with either PI or NNRTI on
      RCT in circulating monocytes in vivo and how this impact correlates with changes in amount
      and size of circulating HDL-c.
observational model: Cohort
time perspective: Prospective
measure: Change in ABCA1 mRNA expression in monocytes
time frame: June 2013
study pop: 
sampling method: Probability Sample
criteria: 
gender: All
minimum age: 18 Years
maximum age: N/A
healthy volunteers: No
last name: Patrick WG Mallon, FRACP FRCPI PhD
role: Principal Investigator
affiliation: HIV Molecular Research Group, UCD School of Medicine and Medical Sciences. Department of Infectious Diseases, Mater Misericordiae University Hospital and Mater Private Hospital
last name: Patrick WG Mallon, MB BCh FRACP FRCPI PhD
phone: +353 716 6311
email: paddy.mallon@ucd.ie
facility: 
status: Recruiting
contact: 
contact backup: 
investigator: 
investigator: 
country: United Kingdom
responsible party type: Principal Investigator
investigator affiliation: University College Dublin
investigator full name: Patrick Mallon
investigator title: Associate Dean for Research and Innovation UCD School of Medicine and Medical Sciences, Consultant Infectious Diseases Physician
mesh term: Dyslipidemias