RecruitingPhase 1/2

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

United States70 participantsStarted 2023-05-17

Plain-language 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).

Who can participate

Age range18 Years – 80 Years

SexALL

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AI-rewrites the medical criteria so a patient or caregiver can understand them. Always confirm with the trial site.

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 Coumad…

What they're measuring

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.

Timeframe: Through study completion date, an average of 5 years.

Change in cross-sectional differences and 24-month longitudinal changes in synaptic density in PLWH on suppressive ART relative to matched HIV-negative controls

Timeframe: Baseline and 24 months

Trial details

NCT IDNCT05586581

SponsorYale University

Sponsor typeOTHER

Study typeINTERVENTIONAL

Primary completion2027-12

Contact for this trial

Allison Nelson, RN

(475) 434-4324 allison.nelson@yale.edu

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