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

NCT03581305 | Completed Phase 1 Results FDA Drug

• 2 other identifiers: 18011718-CC-0117
• Study Type: interventional
• Target: 46
• Locations: 1 country
• Sites: 1

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.

Conditions

Depression; HIV Infections; HIV-Associated Cognitive Motor Complex

Keywords

11C-DASB; 18F-Fluoro-L-dopa; HIV; Depression; Positron Emission Tomography (PET)

Outcome Measures

Primary Outcomes (2)

• Influx Constant (Ki) for 18F-FDOPA PET.

  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.

  90 minutes of scanning

• 11C-DASB PET Binding Potential

  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.

  90 minutes of scanning

Secondary Outcomes (3)

• Correlation of 18F-FDOPA With Co-morbidities

  Study and statistical analysis Completion

• Correlation of 18F-FDOPA and 11C-DASB With HIV

  Study and statistical analysis Completion

• Correlation of 11C-DASB With Neuropsychiatric Evaluation

  Study and statistical analysis Completion

Study Arms (2)

Dopaminergic arm

ACTIVE COMPARATOR

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

Drug: 18F-FDOPA

Serotonergic arm

ACTIVE COMPARATOR

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

Drug: 11C-DASB

Interventions

18F-FDOPA DRUG

High resolution positron emission tomography (PET) of the brain and radioligands targeted against the dopaminergic (18F-FDOPA) system.

Dopaminergic arm

11C-DASB DRUG

High resolution positron emission tomography (PET) of the brain and radioligands targeted against the serotonergic (11C-DASB) system.

Serotonergic arm

Eligibility Criteria

• Age: 18 Years - 70 Years
• Sex: all
• Healthy Volunteers: Yes
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Subject groups:
• 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:
• Group D: HIV-positive subjects with or without co-morbidities
• Group E: HIV-negative subjects with or without co-morbidities
• All Subjects (Groups A-E):
• Men and women, 18-70 years of age
• Ability to sign informed consent by the subject
• Subjects may be enrolled in or have been discharged from IRB approved NIH protocols OR subjects may be referred from outside providers/institutions.
• Has the ability to be seen by an outside medical doctor who provides care.
• All HIV-positive Subjects with or without co- morbidities (Groups A \[dopaminergic arm, n=25)\] and Group D \[serotonergic arm, n=20\])
• Known and documented HIV-1 infection

You may not qualify if:

• All Subjects (Groups A-E):
• Illness or other condition that, in the opinion of the PI, may interfere with study participation at the time of enrollment, including known history of significant intracranial structural damage such as previous stroke(s) or history of intracranial benign or malignant tumors.
• Conditions other than HAND associated with cognitive impairment or dementia such as Alzheimer s, Parkinson s disease, head injury with loss of consciousness \>30 minutes, or seizure disorders.
• A positive screening result for psychiatric diseases that are known to affect the dopaminergic or serotonergic systems.
• Current substance abuse that would interfere with PET scan results at the investigators discretion.
• Medications: use of any drug with known dopaminergic or serotonergic activity within 6 months prior to planned imaging date(s).
• Pregnant or Lactating women: Women of childbearing potential must have a negative serum or urine pregnancy test within 1 week prior to study entry. Pregnancy testing will also be performed in enrolled female participants prior to any radiation exposure.
• Prior or planned/anticipated exposure to radiation due to clinical care or participation in other research protocols, which would exceed the recommended acceptable annual limit of radiation exposure once accounting for the requirements of the current study.
• Use of any of the following drugs within 6 months from planned imaging date(s):
• Haloperidol (increased intracerebral dopamine turnover caused by haloperidol may result in increased accumulation of 18F-DOPA)
• Monoamine oxidase (MAO) inhibitors (may result in increased accumulation of 18F-DOPA in the brain)
• Reserpine (reserpine-induced depletion of the contents of intraneuronal vesicles may prevent retention of 18F-DOPA in the brain)
• Carbidopa/LDOPA (LDOPA competes with 18F-DOPA for DOPA decarboxylase activity)
• Allergy to carbidopa

Sponsors & Collaborators

• National Institutes of Health Clinical Center (CC): lead

Study Sites (1)

National Institutes of Health Clinical Center

Bethesda, Maryland, 20892, United States

Location

Related Links

• NIH Clinical Center Detailed Web Page

MeSH Terms

Conditions

Depression; HIV Infections; AIDS Dementia Complex

Interventions

fluorodopa F 18; 3-amino-4-(2-dimethylaminomethylphenylsulfanyl)benzonitrile

Condition Hierarchy (Ancestors)

Behavioral Symptoms; Behavior; Blood-Borne Infections; Communicable Diseases; Infections; Sexually Transmitted Diseases, Viral; Sexually Transmitted Diseases; Lentivirus Infections; Retroviridae Infections; RNA Virus Infections; Virus Diseases; Genital Diseases; Urogenital Diseases; Immunologic Deficiency Syndromes; Immune System Diseases; Dementia; Brain Diseases; Central Nervous System Diseases; Nervous System Diseases; Neurocognitive Disorders; Mental Disorders

Results Point of Contact

• Title: Dima Hammoud, Senior investigator
• Organization: NIH/CC

hammoudd@cc.nih.gov

3014023041

Study Officials

• Dima A Hammoud, M.D.

  National Institutes of Health Clinical Center (CC)

  PRINCIPAL INVESTIGATOR

Publication Agreements

• PI is Sponsor Employee: Yes

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NON RANDOMIZED
• Masking: NONE
• Purpose: BASIC SCIENCE
• Intervention Model: PARALLEL
• Sponsor Type: NIH
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: July 7, 2018
• First Posted: July 10, 2018
• Study Start: November 20, 2018
• Primary Completion: April 6, 2022
• Study Completion: April 6, 2022
• Last Updated: March 21, 2023
• Results First Posted: March 21, 2023

Record last verified: 2022-04-07

Data Sharing

• IPD Sharing: Will not share

Locations

US (1)