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

• Status: Not yet recruiting
• Trial end date: 2030-12-01
• Target enrollment: 0
• Participant gender: All

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).

• Phase: Phase 1/Phase 2
• Accepts Healthy Volunteers?: Accepts Healthy Volunteers

Details

• Lead Sponsor: Yale University
• Collaborators: National Institute of Mental Health (NIMH); National Institutes of Health (NIH)

Criteria

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 & Surveys.

PLWH Exclusion Criteria:

• Active substance dependence (e.g., heroin, alcohol, cocaine, sedative hypnotics, methamphetamine) as determined by the standardized Behavioral Assessments.

• A history of significant non-HIV related neurological illness (e.g., cerebrovascular, seizures, traumatic brain injury).

• Medical contraindications to the administration of radioactivity (e.g., prior radiation exposure within the past year from research, or from workplace exposure, that in combination with the planned scans would exceed the FDA limit for annual radiation exposure).

• Medical contraindications to participation in a magnetic resonance imaging procedure (e.g., ferromagnetic implants/foreign bodies, claustrophobia, cardiac pacemaker, prosthetic valve, otologic implant, etc.).

• History of a bleeding disorder, low platelet count, or are currently taking anticoagulants (such as Coumadin, Heparin, Pradaxa, Xarelto).

HIV - 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.

• Willingness to participate in phlebotomy, NPT Assessments & Surveys, MRI, and PET.

• Physically healthy by medical history, physical, neurological, and laboratory examinations, as judged by the principal investigator.

• Have a negative test for HIV on file within the last three months or willing to have an HIV test in the current study.

HIV- Exclusion Criteria:

• Active substance dependence (e.g., heroin, alcohol, cocaine, sedative hypnotics, methamphetamine) as determined by the standardized Behavioral Assessments.

• A history of significant neurological illness (e.g., cerebrovascular, seizures, traumatic brain injury).

• Medical contraindications to the administration of radioactivity (e.g., prior radiation exposure within the past year, from research, or from workplace exposure, that in combination with the planned scans would exceed the FDA limit for annual radiation exposure)

• Medical contraindications to participation in a magnetic resonance imaging procedure (e.g., ferromagnetic implants/foreign bodies, claustrophobia, cardiac pacemaker, prosthetic valve, otologic implant, etc.

• History of a bleeding disorder or are currently taking anticoagulants (such as Coumadin, Heparin, Pradaxa, Xarelto