PET Imaging of Synaptic Density Combined With Neuroimmunologic Measures to Reveal Mechanisms of HIV Neuropathogenesis During ART

Status: Recruiting
Location: See location...
Intervention Type: Drug
Study Type: Interventional
Study Phase: Phase 1/Phase 2
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).

Eligibility
Participation Requirements
Sex: All
Minimum Age: 18
Maximum Age: 80
Healthy Volunteers: t
View:

• 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.

• 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.

Locations
United States
Connecticut
Yale School of Medicne, Neuro ID Research Program
RECRUITING
New Haven
Contact Information
Primary
Allison Nelson, RN
allison.nelson@yale.edu
(475) 434-4324
Backup
Paige Ryall
paige.ryall@yale.edu
(475) 375-7424
Time Frame
Start Date: 2023-05-17
Estimated Completion Date: 2030-12
Participants
Target number of participants: 70
Treatments
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.
Sponsors
Leads: Yale University
Collaborators: National Institute of Mental Health (NIMH), National Institutes of Health (NIH)

This content was sourced from clinicaltrials.gov