Imaging brain changes in people with HIV on treatment

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

This study is trying to see how HIV treatment affects brain changes over two years in people with HIV compared to healthy individuals.

Quick facts

• Phase: PHASE1; PHASE2
• Study type: Interventional
• Enrollment: 70 (estimated)
• Ages: 18 Years to 80 Years
• Sex: All
• Sponsor: Yale University (other)
• Drugs / interventions: cART, radiation
• Locations: 1 site (New Haven, Connecticut)
• Trial ID: NCT05586581 on ClinicalTrials.gov

What this trial studies

This study aims to evaluate changes in synaptic density in the brains of individuals living with HIV who are on antiretroviral therapy using advanced imaging techniques, including positron-emission tomography (PET) and magnetic resonance imaging (MRI). It will compare these changes over a 24-month period between people with HIV and matched healthy controls. The study will also investigate the relationship between microglial levels and synaptic density, providing insights into the mechanisms of HIV-related brain injury. Participants will undergo multiple imaging sessions and clinical assessments to gather comprehensive data.

Who should consider this trial

Good fit: Ideal candidates are individuals living with HIV who have been on effective antiretroviral therapy for at least one year and are willing to participate in imaging and neuropsychological assessments.

Not a fit: Patients with active substance dependence or significant non-HIV related neurological illnesses may not benefit from this study.

Why it matters

Potential benefit: If successful, this study could lead to improved understanding and management of HIV-associated neurocognitive disorders.

How similar studies have performed: Other studies have shown promising results using similar imaging approaches to assess brain changes in HIV, but this specific combination of techniques is novel.

Eligibility 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

Where this trial is running

New Haven, Connecticut

• Yale School of Medicne, Neuro ID Research Program — New Haven, Connecticut, United States (RECRUITING)

Study contacts

• Principal investigator: Serena Spudich, MD — Yale University
• Study coordinator: Allison Nelson, RN

Conditions: HIV Associated Neurocognitive Disorder, HIV Dementia, HIV Encephalitis, Healthy, Human immunodeficiency virus, Positron-Emission Tomography Imaging, Magnetic Resonance Imaging, Cerebrospinal Fluid