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Phase 1 N=46 Basic Science

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

Depression · HIV Infections · HIV-Associated Cognitive Motor Complex

Enrolled (actual)
46
Serious AEs
0.0%
Results posted
Mar 2023
Primary outcome: Primary: Influx Constant (Ki) for 18F-FDOPA PET. — 0.01415; 0.01409; 0.01588; 0.01592 min-1

Study Design & Population

Study type
Interventional
Phase
Phase 1
Interventions
18F-FDOPA (Drug); 11C-DASB (Drug)
Age
Adult, Older Adult · 18+ yrs
Sex
All
Sponsor
National Institutes of Health Clinical Center (CC)
Primary completion
Apr 2022

Outcome Measures

OutcomeResultp-value
PRIMARY
Influx Constant (Ki) for 18F-FDOPA PET.
0.01415; 0.01409; 0.01588; 0.01592
PRIMARY
11C-DASB PET Binding Potential
2.949; 3.256
SECONDARY
Correlation of 18F-FDOPA With Co-morbidities
SECONDARY
Correlation of 18F-FDOPA and 11C-DASB With HIV
SECONDARY
Correlation of 11C-DASB With Neuropsychiatric Evaluation

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.

Eligibility Criteria

  • INCLUSION CRITERIA:

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
  • Plasma HIV-RNA BLD ( 7.5% (7.5 % score is the threshold for starting statin therapy as per the 2013 American College of Cardiology [ACC] / American Heart Association [AHA] guidelines).

HIV-negative Subjects WITHOUT co-morbidities (Group C, n=25)

  • HIV-antibody negative
  • No history of any of the following:
  • Hypertension, as defined by treatment with medications for hypertension or with a systolic blood pressure at screening greater than or equal to 140mm Hg.
  • Diabetes mellitus, as defined HgbA1C greater than or equal to 6.5% or treatment for diabetes.
  • Hepatitis C infection as documented by lab results of positive Hepatitis C antibody and/or detectable Hepatitis C viral load. Subjects who responded to HCV treatment (SVR) will not be included.
  • History of previous drug abuse.
  • History of previous alcoholism. Alcoholism is based on alcohol having affected the subject s work or home life.
  • Clinical ASCVD (e.g. history of acute coronary syndromes, or myocardial infarction, stable or unstable angina, coronary or other arterial revascularization or peripheral arterial disease of atherosclerotic origin) and/or 10-year heart disease risk score (ASCVD risk score) >7.5% (7.5 % score is the threshold for starting statin therapy as per the 2013 ACC/AHA guidelines 35).
  • Any other disease entities including chronic infections (e.g. Hepatitis B, Lyme disease), neurological diseases (e.g. Multiple sclerosis, vasculitis) or systemic diseases (e.g. Sjogren s diseases, sarcoidosis, systemic lupus erythematosus [SLE]) that in the opinion of the investigator would be considered a significant co-morbidity.

HIV-negative Subjects with or without co- morbidities (Group E, n=20)

  • HIV-antibody negative

EXCLUSION CRITERIA

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
View full record on ClinicalTrials.gov →

Data sourced from ClinicalTrials.gov (NCT03581305). Outcome figures and adverse-event rates are extracted automatically from the registry's posted results and are provided for clinician reference, not as a substitute for the primary publication.

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