<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/NCT02234492</url>
  </required_header>
  <id_info>
    <org_study_id>20140263-01H</org_study_id>
    <nct_id>NCT02234492</nct_id>
  </id_info>
  <brief_title>The Effects of Statin Therapy on Coronary Flow Reserve and Inflammatory Markers in HIV-Positive Patients</brief_title>
  <official_title>The Effects of Statin Therapy on Coronary Flow Reserve and Inflammatory Markers in HIV-Positive Patients</official_title>
  <sponsors>
    <lead_sponsor>
      <agency>Ottawa Heart Institute Research Corporation</agency>
      <agency_class>Other</agency_class>
    </lead_sponsor>
    <collaborator>
      <agency>Ontario HIV Treatment Network</agency>
      <agency_class>Other</agency_class>
    </collaborator>
  </sponsors>
  <source>Ottawa Heart Institute Research Corporation</source>
  <oversight_info>
    <has_dmc>No</has_dmc>
  </oversight_info>
  <brief_summary>
    <textblock>
      The purpose of this study is to determine whether the use of rosuvastatin in Human&#xD;
      Immunodeficiency Virus (HIV) infected individuals lowers inflammation in blood vessels,&#xD;
      improves blood circulation in the small arteries that provide nutrients to the heart muscle&#xD;
      and improves neurocognitive function.&#xD;
    </textblock>
  </brief_summary>
  <detailed_description>
    <textblock>
      HIV is a chronic inflammatory disease. Patients with HIV are at a high risk of cardiovascular&#xD;
      disease (CVD) which may be related to this state of chronic inflammation. HIV infected&#xD;
      individuals are at up to four times higher risk of suffering a heart attack (also know as&#xD;
      acute coronary syndrome).&#xD;
&#xD;
      The medicine rosuvastatin, commonly used to treat high cholesterol, has been shown to reduce&#xD;
      inflammation in arteries in the general population and also in patients with high risk for&#xD;
      heart problems.&#xD;
&#xD;
      72 subjects with HIV infection will be enrolled and divided into 2 groups of 36.&#xD;
&#xD;
      Group 1: Treatment Group: Participants will receive a low dose of rosuvastatin, 10mg, for 6&#xD;
      months in addition to their current medical therapy.&#xD;
&#xD;
      Group 2: Control Group: Participants will not receive rosuvastatin for 6 months and will&#xD;
      continue with their current medical therapy.&#xD;
&#xD;
      Participants in both groups will undergo blood tests, Myocardial Contrast Echocardiography&#xD;
      (MCE) scan and a Positron Emission Tomography/Computed Tomography PET/CT scan using a&#xD;
      radioactive tracer called fluorodeoxyglucose (FDG-PET), monocyte and serum cytokine studies&#xD;
      at baseline and 6 months.&#xD;
&#xD;
      10 subjects without HIV will also be enrolled to undergo monocyte and serum cytokine blood&#xD;
      tests only, for comparison.&#xD;
    </textblock>
  </detailed_description>
  <overall_status>Completed</overall_status>
  <start_date>September 2014</start_date>
  <completion_date type="Actual">October 2018</completion_date>
  <primary_completion_date type="Actual">October 2018</primary_completion_date>
  <phase>Phase 4</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>Diagnostic</primary_purpose>
    <masking>None (Open Label)</masking>
  </study_design_info>
  <primary_outcome>
    <measure>Correlation between coronary flow reserve (CFR) and maximum target to background ratio (TBRmax).</measure>
    <time_frame>At baseline</time_frame>
    <description>At baseline, correlation between CFR by MCE and vascular inflammation (TBRmax) by FDG-PET/CT will be assessed. We anticipate good overall concurrence.</description>
  </primary_outcome>
  <secondary_outcome>
    <measure>Change in CFR</measure>
    <time_frame>At 6 months</time_frame>
    <description>Changes in CFR as measured by MCE will be evaluated over six months in HIV+ patients on ART and treated with rosuvastatin versus those not on a statin. Our study will be one of the first to examine the effects of rosuvastatin on measures of both inflammation and CFR in HIV+ patients.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Change in TBRmax.</measure>
    <time_frame>At 6 months</time_frame>
    <description>Changes in vascular inflammation (TBRmax) as measured by FDG-PET/CT will be evaluated over six months in HIV+ patients on ART and treated with rosuvastatin versus those not on a statin.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Change in neurocognitive function</measure>
    <time_frame>At 6 months</time_frame>
    <description>Changes in neurocognitve function as measured by a neuropsychological test battery (AMS-III Spatial Span, WAIS-R Digit Symbol, Hopkins Verbal Learning Test, Grooved Pegboard, Trail Making Tests A&amp;B, Letter Numbering Sequencing , Patient's Assessment of Own Functioning, Center for Epidemiologic Studies-Depression Scale) will be evaluated over six months .</description>
  </secondary_outcome>
  <number_of_arms>2</number_of_arms>
  <enrollment type="Actual">35</enrollment>
  <condition>Human Immunodeficiency Virus (HIV)</condition>
  <condition>Cardiovascular Disease (CVD)</condition>
  <arm_group>
    <arm_group_label>Rosuvastatin</arm_group_label>
    <arm_group_type>Active Comparator</arm_group_type>
    <description>Rosuvastatin 10mg once daily for 6 months.</description>
  </arm_group>
  <arm_group>
    <arm_group_label>No rosuvastatin</arm_group_label>
    <arm_group_type>No Intervention</arm_group_type>
    <description>No rosuvastatin- this group will continue with their current medical therapy for 6 months.</description>
  </arm_group>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>Rosuvastatin</intervention_name>
    <description>Comparison of rosuvastatin to no rosuvastatin</description>
    <arm_group_label>Rosuvastatin</arm_group_label>
    <other_name>Crestor</other_name>
  </intervention>
  <eligibility>
    <criteria>
      <textblock>
        Inclusion Criteria:&#xD;
&#xD;
          -  40-90 years of age&#xD;
&#xD;
          -  documented evidence of HIV infection&#xD;
&#xD;
          -  on standard antiretroviral therapy(ART) for &gt;1 years&#xD;
&#xD;
          -  viral load persistently below the limits of detection while on ART&#xD;
&#xD;
          -  current Cluster of Differentiation Antigen 4 (CD4) count &gt;350 cells/microlitre&#xD;
&#xD;
          -  baseline Framingham risk score of 10-20%&#xD;
&#xD;
        Exclusion Criteria:&#xD;
&#xD;
          -  uncontrolled diabetes mellitus (glycated hemoglobin (HbA1C) &gt;6.5% or fasting glucose&#xD;
             &gt;7.0 mmol/L)&#xD;
&#xD;
          -  uncontrolled hypertension (systolic blood pressure &gt;160 or diastolic blood pressure&#xD;
             &gt;90)&#xD;
&#xD;
          -  known coronary artery disease (CAD) e.g. previous myocardial infarction,&#xD;
             revascularization procedure, or history of angina&#xD;
&#xD;
          -  chronic renal failure (glomerular filtration rate (GFR) &lt;60 ml/min)&#xD;
&#xD;
          -  total cholesterol &gt;5.8 mmol/L&#xD;
&#xD;
          -  Low-density lipoprotein (LDL) cholesterol &gt;4.0 mmol/L&#xD;
&#xD;
          -  already receiving a statin for baseline dyslipidemia&#xD;
&#xD;
          -  pregnant or lactating&#xD;
&#xD;
          -  active untreated Hepatitis B or C&#xD;
&#xD;
          -  diagnosis or clinical evidence of a concomitant inﬂammatory/autoimmune disease&#xD;
&#xD;
          -  patients at baseline demonstrating regional perfusion abnormalities (confined to&#xD;
             individual coronary territories) following stress MCE will be excluded and further&#xD;
             management will be according to local best practice guidelines&#xD;
      </textblock>
    </criteria>
    <gender>All</gender>
    <minimum_age>40 Years</minimum_age>
    <maximum_age>90 Years</maximum_age>
    <healthy_volunteers>Accepts Healthy Volunteers</healthy_volunteers>
  </eligibility>
  <overall_official>
    <last_name>Girish Dwivedi, MD MRCP PhD</last_name>
    <role>Study Director</role>
    <affiliation>University of Ottawa Heart Institute, Harry Perkins Institute of Medical Research</affiliation>
  </overall_official>
  <overall_official>
    <last_name>Gary Small, MD MRCP</last_name>
    <role>Principal Investigator</role>
    <affiliation>Ottawa Heart Institute Research Corporation</affiliation>
  </overall_official>
  <location>
    <facility>
      <name>The Ottawa Hospital-General Campus</name>
      <address>
        <city>Ottawa</city>
        <state>Ontario</state>
        <zip>K1H 8L6</zip>
        <country>Canada</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>University of Ottawa Heart Institute</name>
      <address>
        <city>Ottawa</city>
        <state>Ontario</state>
        <zip>K1Y 4W7</zip>
        <country>Canada</country>
      </address>
    </facility>
  </location>
  <location_countries>
    <country>Canada</country>
  </location_countries>
  <verification_date>October 2018</verification_date>
  <study_first_submitted>August 20, 2014</study_first_submitted>
  <study_first_submitted_qc>September 4, 2014</study_first_submitted_qc>
  <study_first_posted type="Estimate">September 9, 2014</study_first_posted>
  <last_update_submitted>October 3, 2018</last_update_submitted>
  <last_update_submitted_qc>October 3, 2018</last_update_submitted_qc>
  <last_update_posted type="Actual">October 5, 2018</last_update_posted>
  <responsible_party>
    <responsible_party_type>Principal Investigator</responsible_party_type>
    <investigator_affiliation>Ottawa Heart Institute Research Corporation</investigator_affiliation>
    <investigator_full_name>Gary Small</investigator_full_name>
    <investigator_title>Associate Professor in Cardiology and Clinician Investigator</investigator_title>
  </responsible_party>
  <keyword>Human immunodeficiency virus (HIV)</keyword>
  <keyword>Statin therapy</keyword>
  <keyword>Cardiovascular disease (CVD)</keyword>
  <keyword>Coronary Flow Reserve (CFR)</keyword>
  <keyword>Positron Emission Tomography (PET)</keyword>
  <keyword>Myocardial contrast echocardiography (MCE)</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>
    <mesh_term>Cardiovascular Diseases</mesh_term>
    <mesh_term>Immunologic Deficiency Syndromes</mesh_term>
  </condition_browse>
  <intervention_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Rosuvastatin Calcium</mesh_term>
  </intervention_browse>
  <patient_data>
    <sharing_ipd>No</sharing_ipd>
  </patient_data>
  <!-- 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/NCT02234492
org study id: 20140263-01H
nct id: NCT02234492
lead sponsor: 
collaborator: 
has dmc: No
The purpose of this study is to determine whether the use of rosuvastatin in Human
      Immunodeficiency Virus (HIV) infected individuals lowers inflammation in blood vessels,
      improves blood circulation in the small arteries that provide nutrients to the heart muscle
      and improves neurocognitive function.
HIV is a chronic inflammatory disease. Patients with HIV are at a high risk of cardiovascular
      disease (CVD) which may be related to this state of chronic inflammation. HIV infected
      individuals are at up to four times higher risk of suffering a heart attack (also know as
      acute coronary syndrome).

      The medicine rosuvastatin, commonly used to treat high cholesterol, has been shown to reduce
      inflammation in arteries in the general population and also in patients with high risk for
      heart problems.

      72 subjects with HIV infection will be enrolled and divided into 2 groups of 36.

      Group 1: Treatment Group: Participants will receive a low dose of rosuvastatin, 10mg, for 6
      months in addition to their current medical therapy.

      Group 2: Control Group: Participants will not receive rosuvastatin for 6 months and will
      continue with their current medical therapy.

      Participants in both groups will undergo blood tests, Myocardial Contrast Echocardiography
      (MCE) scan and a Positron Emission Tomography/Computed Tomography PET/CT scan using a
      radioactive tracer called fluorodeoxyglucose (FDG-PET), monocyte and serum cytokine studies
      at baseline and 6 months.

      10 subjects without HIV will also be enrolled to undergo monocyte and serum cytokine blood
      tests only, for comparison.
allocation: Randomized
intervention model: Parallel Assignment
primary purpose: Diagnostic
masking: None (Open Label)
measure: Correlation between coronary flow reserve (CFR) and maximum target to background ratio (TBRmax).
time frame: At baseline
description: At baseline, correlation between CFR by MCE and vascular inflammation (TBRmax) by FDG-PET/CT will be assessed. We anticipate good overall concurrence.
measure: Change in CFR
time frame: At 6 months
description: Changes in CFR as measured by MCE will be evaluated over six months in HIV+ patients on ART and treated with rosuvastatin versus those not on a statin. Our study will be one of the first to examine the effects of rosuvastatin on measures of both inflammation and CFR in HIV+ patients.
measure: Change in TBRmax.
time frame: At 6 months
description: Changes in vascular inflammation (TBRmax) as measured by FDG-PET/CT will be evaluated over six months in HIV+ patients on ART and treated with rosuvastatin versus those not on a statin.
measure: Change in neurocognitive function
time frame: At 6 months
description: Changes in neurocognitve function as measured by a neuropsychological test battery (AMS-III Spatial Span, WAIS-R Digit Symbol, Hopkins Verbal Learning Test, Grooved Pegboard, Trail Making Tests A&B, Letter Numbering Sequencing , Patient's Assessment of Own Functioning, Center for Epidemiologic Studies-Depression Scale) will be evaluated over six months .
arm group label: Rosuvastatin
arm group type: Active Comparator
description: Rosuvastatin 10mg once daily for 6 months.
arm group label: No rosuvastatin
arm group type: No Intervention
description: No rosuvastatin- this group will continue with their current medical therapy for 6 months.
intervention type: Drug
intervention name: Rosuvastatin
description: Comparison of rosuvastatin to no rosuvastatin
arm group label: Rosuvastatin
other name: Crestor
criteria: 
gender: All
minimum age: 40 Years
maximum age: 90 Years
healthy volunteers: Accepts Healthy Volunteers
last name: Girish Dwivedi, MD MRCP PhD
role: Study Director
affiliation: University of Ottawa Heart Institute, Harry Perkins Institute of Medical Research
last name: Gary Small, MD MRCP
role: Principal Investigator
affiliation: Ottawa Heart Institute Research Corporation
facility: 
facility: 
country: Canada
responsible party type: Principal Investigator
investigator affiliation: Ottawa Heart Institute Research Corporation
investigator full name: Gary Small
investigator title: Associate Professor in Cardiology and Clinician Investigator
mesh term: Acquired Immunodeficiency Syndrome
mesh term: HIV Infections
mesh term: Cardiovascular Diseases
mesh term: Immunologic Deficiency Syndromes
mesh term: Rosuvastatin Calcium
sharing ipd: No