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DepressionPhase 1NCT03581305

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

A Phase 1 study testing 18F-FDOPA and 11C-DASB in people with Depression and HIV Infections, run by National Institutes of Health Clinical Center (CC) at 1 site in United States.

Completed

Finished. The study has ended and is not enrolling. Results may be posted on the official record.

Official record
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Trial 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. Read more about this study

Who is it for?
Ages 18 to 70 yearsHealthy volunteers can take part
What is being tested?
18F-FDOPA and 11C-DASB
Could I receive a placebo?
No, everyone receives an active treatment
How many people
46 participants
Where
1 siteUnited States
Study dates
20 Nov 2018to 6 Apr 2022
Phase
Phase 1
Are there results?
Yes, posted in the registrySummary in the doctors' view

Key requirements

Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.

  • Ages 18 to 70 years
  • All sexes
  • Healthy volunteers accepted
  • Adult, Older adult

Who may be able to join

  • 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:
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  • 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 (<100 copies/mm3) for greater than one year since the last available documented viral load measurement..
  • At least one year of continuous ART prior to last documented suppressed viral load measurement and no history of ART modification or interruption since then.
  • HIV-negative Subjects WITH Co-morbidities (Group B, n=25)
  • HIV-antibody negative
  • At least one or more of the following criteria:
  • 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 by HgbA1C greater than or equal to 6.5% or known treatment for diabetes.
  • Hepatitis C infection as documented by lab results of a positive Hepatitis C antibody and/or detectable Hepatitis C viral load. Subjects who responded to HCV treatment (SVR) will be included.
  • History of previous but not current drug abuse.
  • History of previous but not current alcoholism (defined as alcohol intake that affect/affected the subject s work or home life).
  • Clinical atherosclerotic cardiovascular disease (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 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)
  • 1. HIV-antibody negative

Who cannot join

  • 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).
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  • 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.
  • Additional Exclusion Criteria for the Dopaminergic Arm (Groups A, B and C):
  • 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
  • Note that HBV is not an exclusion criterion for groups A, B, D or E since it s not known to have direct CNS pathology in the absence of advanced liver disease and cirrhosis.

Trial locations and contacts

1 site in 1 country.

United States1 site
  • National Institutes of Health Clinical Center

    Bethesda, Maryland, 20892

Other trials in United States

About this study

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.

Read more

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.
Read the 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

Being tested
18F-FDOPA, 11C-DASB
Keywords
11C-DASB, 18F-Fluoro-L-dopa, HIV, Depression, Positron Emission Tomography (PET)
Medical subject headings
Depression, HIV Infections, AIDS Dementia Complex

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

  • 18F-FDOPADrug

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

  • 11C-DASBDrug

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

Study groups in NCT03581305
Study groupRoleWhat they receive
Dopaminergic armActive comparator25 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
Receives: Drug: 18F-FDOPA
Serotonergic armActive comparator20 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
Receives: Drug: 11C-DASB

What is being measured

The primary outcome is the main question the study is designed to answer.

  1. 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.

    Measured: 90 minutes of scanning

  2. 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.

    Measured: 90 minutes of scanning

Secondary outcomes (3)
  1. Correlation of 18F-FDOPA With Co-morbidities

    Correlation of 18F-FDOPA uptake in the brain with co-morbidities such as cardiovascular disease

    Measured: Study and statistical analysis Completion

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

    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).

    Measured: Study and statistical analysis Completion

  3. Correlation of 11C-DASB With Neuropsychiatric Evaluation

    Correlation of 11C-DASB with Neuropsychiatric evaluation (e.g. depressive and executive function/cognitive scores).

    Measured: Study and statistical analysis Completion

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

  1. First posted10 Jul 2018
  2. Study start20 Nov 2018
  3. Primary completion6 Apr 2022
  4. Study completion6 Apr 2022

Resources

More details

For doctors and researchers: how the study is designed, who runs it, and its registry IDs.

Study design
Study type
Interventional
Phase
Phase 1
Primary purpose
Basic science
Allocation
Non-randomised
Intervention model
Parallel groups
Masking
None (open label)
Enrolment
46 participants (actual)
IDs, dates and publications
ClinicalTrials.gov ID
NCT03581305
Sponsor's protocol ID
180117
Other IDs
18-CC-0117
Status last verified
7 Apr 2022
First submitted
7 Jul 2018
Last updated
21 Mar 2023
FDA-regulated drug
Yes
FDA-regulated device
No
Individual data sharing
No: No plan for sharing IPD

Questions about this trial

What is this clinical trial studying?

A Phase 1 study testing 18F-FDOPA and 11C-DASB in people with Depression and HIV Infections, run by National Institutes of Health Clinical Center (CC) at 1 site in United States.

The full registered description is in the About this study section and the official record.

Who may be eligible to take part?

The sponsor lists 38 inclusion and 16 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.

Is this clinical trial currently recruiting?

The record says: finished, as of the sponsor's last update on 21 Mar 2023. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 1 site in United States. Whether a site is taking part right now should be confirmed with that site. See every site.

What are the possible benefits and risks?

They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.

What does this phase mean?

Phase 1 studies test a treatment in a small group of people for the first time or in a new way, mainly to check safety and find the right dose.

Not every study follows the same path, and some studies (observational studies, device studies) have no phase.

Are results available for this study?

Yes. Results are posted in the registry (first posted 21 Mar 2023). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.

How can a doctor refer a patient or contact the research team?

The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.

What does the primary outcome measure?

Influx Constant (Ki) for 18F-FDOPA PET. (time frame: 90 minutes of scanning). The study lists 2 primary outcomes in all. It is what the study was designed to measure, not a finding.

Where can I read the original study information?
Does a listing mean the treatment is approved or proven to work?

No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.

How often is this information updated?

AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 21 Mar 2023.

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