<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/NCT01692236</url>
  </required_header>
  <id_info>
    <org_study_id>120200</org_study_id>
    <secondary_id>12-CC-0200</secondary_id>
    <nct_id>NCT01692236</nct_id>
  </id_info>
  <brief_title>Brain Imaging for HIV-Associated Thinking and Mood Disorders</brief_title>
  <official_title>Neurovascular Magnetic Resonance Imaging in the Assessment of HIV-Associated Neurocognitive Disorders</official_title>
  <sponsors>
    <lead_sponsor>
      <agency>National Institutes of Health Clinical Center (CC)</agency>
      <agency_class>NIH</agency_class>
    </lead_sponsor>
    <collaborator>
      <agency>National Institute of Allergy and Infectious Diseases (NIAID)</agency>
      <agency_class>NIH</agency_class>
    </collaborator>
  </sponsors>
  <source>National Institutes of Health Clinical Center (CC)</source>
  <brief_summary>
    <textblock>
      Background:&#xD;
&#xD;
      - Human immunodeficiency virus (HIV) infection appears to cause problems with blood vessel&#xD;
      function. These problems may add to some thinking and mood disorders found in people with HIV&#xD;
      infection. Researchers want to evaluate HIV infected patients to see if blood vessel function&#xD;
      contributes to thinking and mood disorders, such as early dementia and depression. To do so,&#xD;
      they will compare study results between people with and people without HIV infection.&#xD;
&#xD;
      Objectives:&#xD;
&#xD;
        -  To compare the thickness of blood vessel walls between people with and without HIV&#xD;
           infection.&#xD;
&#xD;
        -  To study the relationship between blood vessel thickness and thinking and mood&#xD;
           disorders.&#xD;
&#xD;
      Eligibility:&#xD;
&#xD;
        -  Individuals between 25 and 55 years of age who have HIV infection.&#xD;
&#xD;
        -  Healthy individuals between 25 and 55 years of age.&#xD;
&#xD;
      Design:&#xD;
&#xD;
        -  Participants will be screened with a physical exam and medical history. Blood and urine&#xD;
           samples will be collected.&#xD;
&#xD;
        -  Participants will have imaging studies of the brain and major blood vessels in the head&#xD;
           and neck.&#xD;
&#xD;
        -  Participants will also have neuropsychological testing. These tests will look at memory,&#xD;
           learning and thinking ability, attention, and mood.&#xD;
&#xD;
        -  Participants will have the option of coming back for repeat blood tests every six months&#xD;
           and repeat imaging studies and neuropsychological tests every year, over 1- 4 years&#xD;
           period.&#xD;
    </textblock>
  </brief_summary>
  <detailed_description>
    <textblock>
      With combination antiretroviral therapy, HIV/AIDS has been transformed from a progressive,&#xD;
      usually fatal infection to a manageable chronic condition. Yet, HIV associated neurocognitive&#xD;
      disorders (HAND) pose a significant clinical problem, even among patients with controlled HIV&#xD;
      viremia. There is evidence of accelerated vascular aging and other vascular disorders in&#xD;
      HIV-infected (HIV+) people, and studies suggest an association between vascular disorders and&#xD;
      unfavorable neurocognitive outcomes. Thus, one possible contributing factor to the high rates&#xD;
      of HANDs and depression could be vascular dysfunction, similar to vascular depression and&#xD;
      vascular dementia that occur in elderly non-HIV+ individuals. One commonly used diagnostic&#xD;
      marker of vasculopathy is thickening of the vessel wall. Multiple studies have already&#xD;
      established the correlation between vessel wall thickening and vascular disease&#xD;
      manifestations. This prospective observational study aims to examine the relationships&#xD;
      between neurocognitive and depression outcomes and vessel wall thickness as a marker of&#xD;
      vascular disease in HIV+ adults. We will be using neuropsychological testing, brain imaging,&#xD;
      blood biomarkers, and state-of-the-art high-resolution MR imaging of the carotid vessel&#xD;
      walls. HIV infected patients (n=40) and HIV-negative controls (n=40) will be recruited.&#xD;
      Participants who consent to longitudinal follow-up will be followed for two years with&#xD;
      clinical evaluations every 6 months and repeat imaging studies at 12 and 24 months. Cross&#xD;
      sectional data analysis will compare markers of vascular and neurocognitive disorders between&#xD;
      HIV-infected and HIV-negative participants. The longitudinal data analysis will assess and&#xD;
      compare the temporal progression of vascular disease (imaging and blood biomarker findings)&#xD;
      in relation to changes in neurocognitive and depression scores in both groups.&#xD;
    </textblock>
  </detailed_description>
  <overall_status>Terminated</overall_status>
  <start_date>September 13, 2012</start_date>
  <completion_date>April 4, 2018</completion_date>
  <study_type>Observational</study_type>
  <has_expanded_access>No</has_expanded_access>
  <study_design_info>
    <time_perspective>Prospective</time_perspective>
  </study_design_info>
  <primary_outcome>
    <measure>Neuropsychologic testing scores</measure>
    <time_frame>1-6 years</time_frame>
  </primary_outcome>
  <secondary_outcome>
    <measure>Serum biomarkers of cardiovascular disease and inflammation</measure>
    <time_frame>1-6 years</time_frame>
  </secondary_outcome>
  <secondary_outcome>
    <measure>MRI brain and vascular findings</measure>
    <time_frame>1-6 years</time_frame>
  </secondary_outcome>
  <enrollment type="Actual">84</enrollment>
  <condition>Human Immunodeficiency Virus</condition>
  <condition>Neurocognitive Impairment</condition>
  <eligibility>
    <criteria>
      <textblock>
        -  INCLUSION CRITERIA:&#xD;
&#xD;
        Inclusion criteria for all participants:&#xD;
&#xD;
          1. Age 25-61 years.&#xD;
&#xD;
          2. Willingness to allow stored samples, human leukocyte antigen (HLA) testing, and future&#xD;
             genetic testing.&#xD;
&#xD;
          3. Hemoglobin less than or equal to 9.0 g/dL, HCT less than or equal to 28%, platelets&#xD;
             less than or equal to 50,000/microL.&#xD;
&#xD;
          4. English language fluency (required for neuropsychological testing).&#xD;
&#xD;
        Additional inclusion criteria for HIV+ participants:&#xD;
&#xD;
          1. Documented HIV infection by standard HIV testing. Prior documentation of HIV- antibody&#xD;
             status at the NIH will be accepted in lieu of repeat testing.&#xD;
&#xD;
          2. HIV viral load below the limit of detection on combination antiretroviral therapy for&#xD;
             less than or equal to 1 year.&#xD;
&#xD;
          3. Under the care of a primary care physician.&#xD;
&#xD;
        Additional inclusion criteria for HIV-negative participants:&#xD;
&#xD;
        1. HIV-antibody negative.&#xD;
&#xD;
        EXCLUSION CRITERIA:&#xD;
&#xD;
        Exclusion criteria for all participants:&#xD;
&#xD;
          1. Contraindication to MRI scanning, including pacemakers or other implanted electrical&#xD;
             devices, brain stimulators, some types of dental implants, aneurysm clips (metal clips&#xD;
             on the wall of a large artery), metallic prostheses (including metal pins and rods,&#xD;
             heart valves, and cochlear implants), permanent eyeliner, implanted delivery pump, or&#xD;
             shrapnel fragments.&#xD;
&#xD;
          2. Subjects with a condition precluding entry into scanner and acquisition of scans&#xD;
             (e.g., morbid obesity, claustrophobia, back pain, motion disorders).&#xD;
&#xD;
          3. Glomerular filtration rate &lt;45 mL/min/1.73 m(2) as estimated using the Modified Diet&#xD;
             in Renal Disease equation.&#xD;
&#xD;
          4. Allergy to qadolinium (MRI contrast)&#xD;
&#xD;
          5. Evidence of current or prior central nervous system opportunistic infection(s) and/or&#xD;
             space-occupying lesions such as primary CNS lymphoma.&#xD;
&#xD;
          6. Prior history of intrathecal chemotherapy or radiation therapy to the brain.&#xD;
&#xD;
          7. History of or current diagnosis of systemic vasculitis.&#xD;
&#xD;
          8. Active systemic infection or malignancy requiring therapy.&#xD;
&#xD;
          9. Psychiatric condition interfering with ability to participate in study procedures or&#xD;
             provide informed consent.&#xD;
&#xD;
         10. Patient or provider report of alcohol or drug abuse ongoing or within 3 months prior&#xD;
             to participation.&#xD;
&#xD;
         11. Sickle cell disease (due to known association with vasculopathy).&#xD;
&#xD;
         12. Systolic blood pressure less than or equal to 180 mmHg at screening.&#xD;
&#xD;
         13. Persons infected with hepatitis C virus (HCV) who are being treated or planning to&#xD;
             seek treatment for HCV.&#xD;
&#xD;
         14. Women who are lactating, pregnant, or actively seeking to become pregnant.&#xD;
&#xD;
         15. Other known clinical condition or conditions discovered on MRI that, at the discretion&#xD;
             of the investigators, precludes serial clinical, neuropsychological, or imaging&#xD;
             evaluation.&#xD;
&#xD;
        Additional exclusion criteria for HIV+ participants&#xD;
&#xD;
        1. HIV acquired perinatally (due to potential effects of HIV and antiretroviral therapy on&#xD;
        neurocognitive and vascular development).&#xD;
      </textblock>
    </criteria>
    <gender>All</gender>
    <minimum_age>25 Years</minimum_age>
    <maximum_age>61 Years</maximum_age>
    <healthy_volunteers>Accepts Healthy Volunteers</healthy_volunteers>
  </eligibility>
  <overall_official>
    <last_name>Avindra Nath, M.D.</last_name>
    <role>Principal Investigator</role>
    <affiliation>National Institute of Neurological Disorders and Stroke (NINDS)</affiliation>
  </overall_official>
  <location>
    <facility>
      <name>National Institutes of Health Clinical Center, 9000 Rockville Pike</name>
      <address>
        <city>Bethesda</city>
        <state>Maryland</state>
        <zip>20892</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location_countries>
    <country>United States</country>
  </location_countries>
  <reference>
    <citation>Connor M. Human immunodeficiency virus (HIV) and stroke: targets for intervention. Infect Disord Drug Targets. 2010 Apr;10(2):76-83. doi: 10.2174/187152610790963483.</citation>
    <PMID>20166974</PMID>
  </reference>
  <reference>
    <citation>Highleyman L. Mortality trends: toward a new definition of AIDS? BETA. 2005 Winter;17(2):18-28.</citation>
    <PMID>15828120</PMID>
  </reference>
  <reference>
    <citation>Holtgrave DR. Causes of the decline in AIDS deaths, United States, 1995-2002: prevention, treatment or both? Int J STD AIDS. 2005 Dec;16(12):777-81. doi: 10.1258/095646205774988109.</citation>
    <PMID>16336756</PMID>
  </reference>
  <verification_date>April 4, 2018</verification_date>
  <study_first_submitted>September 20, 2012</study_first_submitted>
  <study_first_submitted_qc>September 20, 2012</study_first_submitted_qc>
  <study_first_posted type="Estimate">September 25, 2012</study_first_posted>
  <last_update_submitted>December 4, 2019</last_update_submitted>
  <last_update_submitted_qc>December 4, 2019</last_update_submitted_qc>
  <last_update_posted type="Actual">December 5, 2019</last_update_posted>
  <responsible_party>
    <responsible_party_type>Sponsor</responsible_party_type>
  </responsible_party>
  <keyword>MRI</keyword>
  <keyword>HIV</keyword>
  <keyword>Neurocognitive Disorders</keyword>
  <keyword>Major Depression</keyword>
  <keyword>Vasculopathy</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>Neurocognitive Disorders</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/NCT01692236
org study id: 120200
secondary id: 12-CC-0200
nct id: NCT01692236
lead sponsor: 
collaborator: 
Background:

      - Human immunodeficiency virus (HIV) infection appears to cause problems with blood vessel
      function. These problems may add to some thinking and mood disorders found in people with HIV
      infection. Researchers want to evaluate HIV infected patients to see if blood vessel function
      contributes to thinking and mood disorders, such as early dementia and depression. To do so,
      they will compare study results between people with and people without HIV infection.

      Objectives:

        -  To compare the thickness of blood vessel walls between people with and without HIV
           infection.

        -  To study the relationship between blood vessel thickness and thinking and mood
           disorders.

      Eligibility:

        -  Individuals between 25 and 55 years of age who have HIV infection.

        -  Healthy individuals between 25 and 55 years of age.

      Design:

        -  Participants will be screened with a physical exam and medical history. Blood and urine
           samples will be collected.

        -  Participants will have imaging studies of the brain and major blood vessels in the head
           and neck.

        -  Participants will also have neuropsychological testing. These tests will look at memory,
           learning and thinking ability, attention, and mood.

        -  Participants will have the option of coming back for repeat blood tests every six months
           and repeat imaging studies and neuropsychological tests every year, over 1- 4 years
           period.
With combination antiretroviral therapy, HIV/AIDS has been transformed from a progressive,
      usually fatal infection to a manageable chronic condition. Yet, HIV associated neurocognitive
      disorders (HAND) pose a significant clinical problem, even among patients with controlled HIV
      viremia. There is evidence of accelerated vascular aging and other vascular disorders in
      HIV-infected (HIV+) people, and studies suggest an association between vascular disorders and
      unfavorable neurocognitive outcomes. Thus, one possible contributing factor to the high rates
      of HANDs and depression could be vascular dysfunction, similar to vascular depression and
      vascular dementia that occur in elderly non-HIV+ individuals. One commonly used diagnostic
      marker of vasculopathy is thickening of the vessel wall. Multiple studies have already
      established the correlation between vessel wall thickening and vascular disease
      manifestations. This prospective observational study aims to examine the relationships
      between neurocognitive and depression outcomes and vessel wall thickness as a marker of
      vascular disease in HIV+ adults. We will be using neuropsychological testing, brain imaging,
      blood biomarkers, and state-of-the-art high-resolution MR imaging of the carotid vessel
      walls. HIV infected patients (n=40) and HIV-negative controls (n=40) will be recruited.
      Participants who consent to longitudinal follow-up will be followed for two years with
      clinical evaluations every 6 months and repeat imaging studies at 12 and 24 months. Cross
      sectional data analysis will compare markers of vascular and neurocognitive disorders between
      HIV-infected and HIV-negative participants. The longitudinal data analysis will assess and
      compare the temporal progression of vascular disease (imaging and blood biomarker findings)
      in relation to changes in neurocognitive and depression scores in both groups.
time perspective: Prospective
measure: Neuropsychologic testing scores
time frame: 1-6 years
measure: Serum biomarkers of cardiovascular disease and inflammation
time frame: 1-6 years
measure: MRI brain and vascular findings
time frame: 1-6 years
criteria: 
gender: All
minimum age: 25 Years
maximum age: 61 Years
healthy volunteers: Accepts Healthy Volunteers
last name: Avindra Nath, M.D.
role: Principal Investigator
affiliation: National Institute of Neurological Disorders and Stroke (NINDS)
facility: 
country: United States
citation: Connor M. Human immunodeficiency virus (HIV) and stroke: targets for intervention. Infect Disord Drug Targets. 2010 Apr;10(2):76-83. doi: 10.2174/187152610790963483.
PMID: 20166974
citation: Highleyman L. Mortality trends: toward a new definition of AIDS? BETA. 2005 Winter;17(2):18-28.
PMID: 15828120
citation: Holtgrave DR. Causes of the decline in AIDS deaths, United States, 1995-2002: prevention, treatment or both? Int J STD AIDS. 2005 Dec;16(12):777-81. doi: 10.1258/095646205774988109.
PMID: 16336756
responsible party type: Sponsor
mesh term: Acquired Immunodeficiency Syndrome
mesh term: HIV Infections
mesh term: Neurocognitive Disorders