Recruiting
Phase 1
Phase 2

SV2A & TSPO

Sponsor:

Yale University

Code:

NCT05586581

Conditions

HIV Associated Neurocognitive Disorder

HIV Dementia

HIV Encephalitis

Healthy

Eligibility Criteria

Sex: All

Age: 18 - 70+

Healthy Volunteers: Accepted

Interventions

SV2A PET

TSPO PET

Study Details

Brief 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).

Conditions

HIV Associated Neurocognitive Disorder

HIV Dementia

HIV Encephalitis

Healthy

Study ID

NCT05586581

Start date

May 17, 2023

Status verified date

Sep, 2025

Completion date

Dec, 2030

Anticipated

Primary completion date

Dec, 2028

Anticipated

Eligibility Criteria

Eligibility Criteria

Sex: All

Age: 18 - 70+

Healthy Volunteers: Accepted

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

Study Design

Enrollment

70 participants

Anticipated

Allocation

Non randomized

Intervention Model

Parallel Assignment

Primary purpose

Basic Science

Interventions and Outcome Measures

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.

Interventions

SV2A PET

SV2A PET scan with radiotracer \[11C\]UCB-J for imaging synaptic density in the brain

TSPO PET

TSPO PET scan with radiotracer \[11C\]PBR28 for imaging of neuroimmune status

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. ]
  • Change in cross-sectional differences and 24-month longitudinal changes in synaptic density in PLWH on suppressive ART relative to matched HIV-negative controls [ Time Frame: Baseline and 24 months ]

Central Contacts and Locations

Central contacts

Allison Nelson, RN

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

Paige Ryall

(475) 375-7424paige.ryall@yale.edu

Locations

Yale School of Medicne, Neuro ID Research Program

Recruiting

New Haven, Connecticut, United States, 06510

Contacts

Allison Nelson, RN

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

NeuroID@yale.edu

More Information

Sponsor

Yale University

Last update posted

Aug 18, 2026

Last verified

Sep, 2025

Keywords

  • Human immunodeficiency virus
  • Positron-Emission Tomography Imaging
  • Magnetic Resonance Imaging
  • Cerebrospinal Fluid
  • SV2A PET
  • TSPO PET
  • Neuro-immune dysfunction
  • Neuro-Inflammation
  • Biomarkers of inflammation
  • Neuronal Injury
  • Neurocognitive functioning
  • Hippocampus
  • Microglia
  • Neuropathogenesis
  • antiretroviral therapy

Trial information was received from ClinicalTrials.gov and was last updated on 2026-09-10. This information was provided to ClinicalTrials.gov by Yale University on 2026-08-18.