SV2A & TSPO PET Imaging Measures to Reveal Mechanisms of HIV Neuropathogenesis During Antiretroviral Therapy

Part of paid clinical trials in New Haven, Connecticut.

Sponsor
Yale University
Study ID
NCT05586581
Phase
PHASE1/PHASE2
Status
Recruiting
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Conditions

  • HIV Associated Neurocognitive Disorder
  • HIV Dementia
  • HIV Encephalitis
  • Healthy

Eligibility Criteria

Sex
ALL
Age
18 Years - 80 Years
Healthy Volunteers
Accepted

Interventions

  • SV2A PET — DRUG
    SV2A PET scan with radiotracer \[11C\]UCB-J for imaging synaptic density in the brain
  • TSPO PET — DRUG
    TSPO PET scan with radiotracer \[11C\]PBR28 for imaging of neuroimmune status

Study Details

The purpose of this study is to longitudinally characterize and evaluate changes in synaptic density in the brain using novel positron-emission tomography (PET) scans; magnetic resonance imaging (MRI), and clinical laboratory markers associated with HIV-related injury in the central nervous system. This study will test hypotheses relating to the presence and mechanisms of aberrant brain structure at the synaptic level in living humans with virologically controlled HIV on antiretroviral therapy. To evaluate associations between PET imaging radiotracers \[11C\]UCB-J, a ligand for presynaptic vesicle protein 2A (SV2A), a vesicle membrane protein expressed in synapses, and PET \[11C\]PBR28 a measure of microglia function in the brain, the Yale PET center has developed an advanced approach of combining multiple distinct ligands in coordinated same-day PET imaging. Additionally, the study will evaluate the associations of this novel synaptic density marker with well-established clinical measures of neurocognitive performance and laboratory measures of blood and cerebrospinal fluid (CSF).

Key Dates

Start date
May 17, 2023
Status verified
Sep 2025
Primary completion
Dec 31, 2027
Completion
Dec 31, 2030

Study Design

Enrollment
70 participants (estimated)
Allocation
NON_RANDOMIZED
Intervention model
PARALLEL
Primary purpose
BASIC_SCIENCE

Arms

  • Experimental: People living with treated suppressed HIV infection (PLWH)
    40 PLWH participants will be scanned using anatomical magnetic resonance imaging (MRI) and undergo two SV2A (11C-UCB-J) PET scans with arterial sampling and full radio metabolite analysis to obtain measures of synaptic density at baseline and 24 months (2 years). For each SV2A PET, up to 20 millicurie (mCi) of \[11C\], UCB-J will be administered by an intravenous line (IV) with a scan duration of up to 120 minutes. A subset of PLWH (n=20) will participate in TSPO (11C-PBR28) PET scans on the same day as the baseline SV2A PET scan. For a TSPO PET, up to 20 mCi of \[11C\], PBR28 will be administered by an intravenous line (IV) with a scan duration of up to 120 minutes.
  • Experimental: HIV-Negative Control (HIV-)
    30 HIV-Negative Control (HIV-) participants will be scanned using anatomical magnetic resonance imaging (MRI) and undergo two SV2A (11C-UCB-J) PET scans with arterial sampling and full radio metabolite analysis to obtain measures of synaptic density at baseline and 24 months (2 years). For each SV2A PET, up to 20 mCi of \[11C\], UCB-J will be administered by an intravenous line (IV) with a scan duration of up to 120 minutes.

Primary Outcome Measure

The primary outcome measure for 11C-UCB-J will be the binding potential of 11C-UCB-J, specifically non-displaceable binding potential (BPND), the ratio of the specifically bound radioligand to that of nondisplaceable radioligand in tissue. [ Time Frame: Through study completion date, an average of 5 years. ]

Central Contacts

Locations (1)

FacilityCityStateZIPSite coordinators
Yale School of Medicne, Neuro ID Research ProgramNew HavenConnecticut06510
Allison Nelson, RN
[email protected]
(475) 434-4324
[email protected]

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Yale School of Medicne, Neuro ID Research Program· New Haven, CT

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