SV2A & TSPO PET Imaging Measures to Reveal Mechanisms of HIV Neuropathogenesis During Antiretroviral Therapy
Trial statusRecruiting
Trial phasePhase 1, Phase 2
Trial typeInterventional
Biological sexAll
Age18-80
SponsorYale University
About this trial
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 criteria
This trial accepts healthy volunteersQualifiers
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.
Disqualifiers
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.).
Trial design
Design model
Parallel
Treatments tested in this trial
SV2A PET
DrugSV2A PET scan with radiotracer \[11C\]UCB-J for imaging synaptic density in the brain
TSPO PET
DrugTSPO PET scan with radiotracer \[11C\]PBR28 for imaging of neuroimmune status
Treatment groups
70 Participants
are divided into 2 treatment groupsGroup A: People living with treated suppressed HIV infection (PLWH)Experimental treatment 2 interventions
Group B: HIV-Negative Control (HIV-)Experimental treatment 1 intervention
Trial outcomes
Primary outcomes
1
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.
Preliminary data from the investigators' pilot study revealed SV2A PET imaging with radiotracer 11C-UCB-J identified regions of reduced synaptic density in suppressed PLWH compared to matched HIV-negative controls. PET and MRI imaging data will be processed for quantification of 11C-UCB-J imaging data in a larger group of suppressed PLWH compared to matched HIV-negative controls to test-retest reproducibility of 11C-UCB-J.
Time frame
Through study completion date, an average of 5 years.2
Change in cross-sectional differences and 24-month longitudinal changes in synaptic density in PLWH on suppressive ART relative to matched HIV-negative controls
Baseline and 24 Month PET and MRI imaging data will be processed for a linear mixed-effects model (LMM) to compare changes in hippocampal-frontostriatal 11C-UCB-J BPND between PLWH and healthy controls.
Time frame
Baseline and 24 monthsSponsors and contacts
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Yale University
Lead sponsor
National Institutes of Health (NIH)
Collaborator
National Institute of Mental Health (NIMH)
Collaborator
Source ClinicalTrials.gov