PET Imaging of Synaptic Density Combined With Neuroimmunologic Measures to Reveal Mechanisms of HIV Neuropathogenesis During ART
Yale University
Summary
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).
Description
The HIV PET plus study builds upon the compelling preliminary findings of the investigators HIV PET pilot study (Yale Internal Review Board (IRB) #2000024620) that brain SV2A PET successfully identifies regions of reduced synaptic density, including a hippocampal-frontostriatal neural circuit that is relevant to central nervous system (CNS) dysfunction in PLWH on ART The primary aims of this study are as follows: Aim 1. To evaluate cross-sectional differences and 24-month longitudinal changes in synaptic density in PLWH on suppressive ART relative to matched HIV-negative (HIV-) controls. Syn…
Eligibility
- Age range
- 18–80 years
- Sex
- All
- Healthy volunteers
- Yes
PLWH Inclusion Criteria: * Voluntary, written, informed consent (signed and dated) * For females, a negative urine or serum pregnancy (HCG) test at screening and on each scan day before initiation of any scan procedures. * HIV infection on cART with documented viral suppression for at least one year. Plasma viral suppression will be defined as no more than one viral load * Test above 20 HIV RNA cps/mL in the year prior to screening and no HIV RNA tests above 200 cps/mL in the same span. * Willingness to participate in MRI, PET, phlebotomy, and Neuropsychological Testing (NPT) Assessments \& S…
Interventions
- DrugSV2A PET
SV2A PET scan with radiotracer \[11C\]UCB-J for imaging synaptic density in the brain
- DrugTSPO PET
TSPO PET scan with radiotracer \[11C\]PBR28 for imaging of neuroimmune status
Location
- Yale School of Medicne, Neuro ID Research ProgramNew Haven, Connecticut