PET Imaging of the Dopaminergic and Serotonergic Systems in Treated HIV Positive Subjects

Phase 1

Completed

Conditions: HIV-Associated Cognitive Motor Complex
Depression
HIV Infections

Interventions: Drug: 18F-FDOPA
Drug: 11C-DASB

Registration Number: NCT03581305

Lead Sponsor: National Institutes of Health Clinical Center (CC)

Brief Summary: Background:

Human immunodeficiency virus (HIV) infection is a serious disease with no cure. Some people with HIV have depression and other mood problems. They can have problems with thinking and memory. Researchers think 2 chemicals in the brain may cause those problems. The chemicals are serotonin and dopamine. The researchers want to take images to learn more about those chemicals in HIV patients.

Objective:

To learn how HIV affects serotonin and dopamine in the brain.

Eligibility:

Adults ages 18-70 with HIV who have been on antiretroviral treatment for at least 1 year

Healthy adults ages 18-70

All participants must be already enrolled in protocol 13-N-0149.

Design:

* Participants will be screened with a urine drug test. The results could be shared with insurance companies.

* Participants who could be pregnant will have a pregnancy test.

* Participants may have a physical exam and blood tests.

* Participants will have 1 or 2 positron emission tomography (PET) scans. A needle will guide a thin plastic tube (catheter) into an arm vein. A radioactive drug will be injected into the plastic tube. This is a tracer that helps researchers understand the PET images.

* Participants who have the dopamine scan will have to fast for 4-6 hours before the scan. They will take a pill to help direct the tracer to the brain one hour before the scan.

* Each scan will last about 1.5 hours.

* Participants will be asked to drink a lot of fluids and empty their bladder frequently for the rest of the day after each scan.

Detailed Description: Background: An extensive body of literature points towards neuronal brain injury in human immunodeficiency virus positive (HIV-positive) subjects despite virological suppression of the virus in the periphery under the effect of antiretroviral therapies (ART). Existing evidence suggests that the central nervous system (CNS) could be an important reservoir for human immunodeficiency virus (HIV) regardless of cumulative time on treatment. This results in progressive neurocognitive dysfunction despite optimal treatment and peripheral control of the infection. Even though structural imaging studies have described abnormalities in optimally-treated HIV-positive subject population, there has been only a few attempts at deciphering the cellular levels of brain damage in those subjects using in vivo molecular imaging biomarkers. As part of CNS involvement, specific neurotransmitter systems including the dopaminergic and serotonergic systems are thought to be affected by the infection with distinct neurological, cognitive and psychological manifestations, even in optimally-treated subjects.

Objective: This protocol aims at identifying aspects of dopaminergic and serotonergic dysfunction in optimally-treated HIV-positive subjects using high resolution positron emission tomography (PET) of the brain and radioligands targeted against the dopaminergic (18F-FDOPA) and serotonergic (11C-DASB) systems.

Study population: We will identify 25 eligible HIV-infected individuals and 50 eligible HIV-negative (HIV-) individuals for the dopaminergic arm, and 20 HIV-infected individuals and 20 HIV-negative individuals for the serotonergic arm. Subjects will be selected from IRB approved NIH protocols, self-referred or will be referred form outside providers/institutions and those who meet eligibility criteria will be offered enrollment in our study.

Design: Subjects will undergo either a one-time 18F-FDOPA PET scan or a one-time 11C-DASB PET scan or both, if eligible. HIV-positive subjects and HIV-negative individuals will be included in the study.

Outcome Measures: Influx constant (Ki) for 18F-FDOPA PET and Binding potential relative to

non-displaceable binding (BPND) values for 11C-DASB PET

Recruitment & Eligibility

Status: COMPLETED

Sex: All

Target Recruitment: 46

Inclusion Criteria

Not provided

Exclusion Criteria

Not provided

Study & Design

Study Type: INTERVENTIONAL

Study Design: PARALLEL

Arm && Interventions

Group	Intervention	Description
Dopaminergic arm	18F-FDOPA	25 eligible HIV-infected individuals and 50 eligible HIV-negative (HIV-) individuals for the dopaminergic arm. Dopaminergic arm: Group A: HIV-positive subjects with or without co- morbidities; Group B: HIV-negative subjects with co-morbidities; Group C: HIV-negative subjects without co-morbidities
Serotonergic arm	11C-DASB	20 HIV-infected individuals and 20 HIV-negative individuals for the serotonergic arm Serotonergic arm: Group D: HIV-positive subjects with or without co-morbidities; Group E: HIV-negative subjects with or without co-morbidities

Primary Outcome Measures

Name	Time	Method
Influx Constant (Ki) for 18F-FDOPA PET.	90 minutes of scanning	in order to learn how HIV affects dopamine in the brain, we performed dynamic PET scans for 90 minutes in each patient, after injection of FDOPA. Analysis: After the scans were reconstructed, we extracted the Time activity curves and performed compartmental analysis using Patlak linear graphical analysis with reference region. The extracted outcome measure is the influx constant referred to as Ki and reflecting the rate of FDOPA uptake in specific brain regions.
11C-DASB PET Binding Potential	90 minutes of scanning	Binding potential is a measure of the density of available serotonin transporter in specific brain locations. This is extracted from time activity curves of dynamic PET data acquired over 90 minutes after injection of 11C-DASB.

Secondary Outcome Measures

Name	Time	Method
Correlation of 18F-FDOPA With Co-morbidities	Study and statistical analysis Completion	Correlation of 18F-FDOPA uptake in the brain with co-morbidities such as cardiovascular disease
Correlation of 18F-FDOPA and 11C-DASB With HIV	Study and statistical analysis Completion	Correlation of 18F-FDOPA and 11C-DASB with HIV infection parameters (e.g. time since HIV diagnosis, duration of infection before treatment initiation, nadir CD4).
Correlation of 11C-DASB With Neuropsychiatric Evaluation	Study and statistical analysis Completion	Correlation of 11C-DASB with Neuropsychiatric evaluation (e.g. depressive and executive function/cognitive scores).