PET Imaging of the Dopaminergic and Serotonergic Systems in Treated HIV Positive Subjects
Condition: Depression; HIV Infections; HIV-Associated Cognitive Motor Complex
MeSH terms: AIDS Dementia Complex; Depression
Study type: Interventional
Phase: Phase 1

Summary: 
      Background:

      Human immunodeficiency virus (HIV) infection is a serious disease with no cure. Some people
      with HIV have depression and other mood problems. They can have problems with thinking and
      memory. Researchers think 2 chemicals in the brain may cause those problems. The chemicals
      are serotonin and dopamine. The researchers want to take images to learn more about those
      chemicals in HIV patients.

      Objective:

      To learn how HIV affects serotonin and dopamine in the brain.

      Eligibility:

      Adults ages 18-70 with HIV who have been on antiretroviral treatment for at least 1 year

      Healthy adults ages 18-70

      All participants must be already enrolled in protocol 13-N-0149.

      Design:

        -  Participants will be screened with a urine drug test. The results could be shared with
           insurance companies.

        -  Participants who could be pregnant will have a pregnancy test.

        -  Participants may have a physical exam and blood tests.

        -  Participants will have 1 or 2 positron emission tomography (PET) scans. A needle will
           guide a thin plastic tube (catheter) into an arm vein. A radioactive drug will be
           injected into the plastic tube. This is a tracer that helps researchers understand the
           PET images.

        -  Participants who have the dopamine scan will have to fast for 4-6 hours before the scan.
           They will take a pill to help direct the tracer to the brain one hour before the scan.

        -  Each scan will last about 1.5 hours.

        -  Participants will be asked to drink a lot of fluids and empty their bladder frequently
           for the rest of the day after each scan.
    

Detailed description: 
      Background: An extensive body of literature points towards neuronal brain injury in human
      immunodeficiency virus positive (HIV-positive) subjects despite virological suppression of
      the virus in the periphery under the effect of antiretroviral therapies (ART). Existing
      evidence suggests that the central nervous system (CNS) could be an important reservoir for
      human immunodeficiency virus (HIV) regardless of cumulative time on treatment. This results
      in progressive neurocognitive dysfunction despite optimal treatment and peripheral control of
      the infection. Even though structural imaging studies have described abnormalities in
      optimally-treated HIV-positive subject population, there has been only a few attempts at
      deciphering the cellular levels of brain damage in those subjects using in vivo molecular
      imaging biomarkers. As part of CNS involvement, specific neurotransmitter systems including
      the dopaminergic and serotonergic systems are thought to be affected by the infection with
      distinct neurological, cognitive and psychological manifestations, even in optimally-treated
      subjects.

      Objective: This protocol aims at identifying aspects of dopaminergic and serotonergic
      dysfunction in optimally-treated HIV-positive subjects using high resolution positron
      emission tomography (PET) of the brain and radioligands targeted against the dopaminergic
      (18F-FDOPA) and serotonergic (11C-DASB) systems.

      Study population: We will identify 25 eligible HIV-infected individuals and 50 eligible
      HIV-negative (HIV-) individuals for the dopaminergic arm, and 20 HIV-infected individuals and
      20 HIV-negative individuals for the serotonergic arm. Subjects will be selected from IRB
      approved NIH protocols, self-referred or will be referred form outside providers/institutions
      and those who meet eligibility criteria will be offered enrollment in our study.

      Design: Subjects will undergo either a one-time 18F-FDOPA PET scan or a one-time 11C-DASB PET
      scan or both, if eligible. HIV-positive subjects and HIV-negative individuals will be
      included in the study.

      Outcome Measures: Influx constant (Ki) for 18F-FDOPA PET and Binding potential relative to

      non-displaceable binding (BPND) values for 11C-DASB PET
    

Intervention name(s): 18F-FDOPA; 11C-DASB
Intervention type(s): Drug; Drug
Intervention description(s): High resolution positron emission tomography (PET) of the brain and radioligands targeted against the dopaminergic (18F-FDOPA) system.; High resolution positron emission tomography (PET) of the brain and radioligands targeted against the serotonergic (11C-DASB) system.
Allocation: Non-Randomized
Intervention model: Parallel Assignment
Masking: None (Open Label)
Primary purpose: Basic Science
Keywords: 11C-DASB; 18F-Fluoro-L-dopa; HIV; Depression; Positron Emission Tomography (PET)