- ICH GCP
- US Clinical Trials Registry
- Clinical Trial NCT02152670
Understanding Dopamine Mechanisms in Cocaine Addiction Using AMPT and Methylphenidate With [11C]RAC/[11C]PHNO PET
February 14, 2023 updated by: Yale University
Studies using positron emission tomography (PET) have been used with great success in demonstrating specific abnormalities in several facets of dopaminergic system function in human populations (Narendran and Martinez 2009).
Among the first, most consistent, and broadly replicated of such findings in drug- (including cocaine) dependent individuals has been the reduction in subcortical (striatal) D2/3 receptors as imaged, most commonly, by the reversible, non-selective, D2/3 receptor antagonist radiotracer, [11C]raclopride.
Certain dissociations on D2/3 availability by radioligand ([11C]raclopride vs. [11C]PHNO) and by brain region (striatum vs. SN; terminal vs. somatodendritic, respectively) are poorly understood in relationship to prior antagonist tracer results.
In the current study the investigators will use pharmacological interventions (AMPT and methylphenidate) with both antagonist and agonist radiotracers to experimentally reconcile these discordant findings and clarify potential mechanistic inter-relationships.
Study Overview
Status
Terminated
Conditions
Intervention / Treatment
Study Type
Interventional
Enrollment (Actual)
1
Phase
- Not Applicable
Contacts and Locations
This section provides the contact details for those conducting the study, and information on where this study is being conducted.
Study Locations
-
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Connecticut
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New Haven, Connecticut, United States, 06519
- Connecticut Mental Health Center
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-
Participation Criteria
Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.
Eligibility Criteria
Ages Eligible for Study
18 years to 50 years (Adult)
Accepts Healthy Volunteers
Yes
Genders Eligible for Study
All
Description
Inclusion Criteria:
- age 18 - 50 years,
- voluntary, written, informed consent,
- physically healthy by medical history, physical, neurological, ECG, and laboratory examinations,
- for females, non-lactating, no longer of child-bearing potential (or agree to practice effective contraception during the study), and a negative serum pregnancy (B-HCG) test.
- English speaking
- No other major Axis DSM-IV diagnosis present, besides required as below
Inclusion criteria for cocaine dependent:
- DSM-IV criteria for Cocaine Abuse (305.60) or Cocaine Dependence (304.20)
- recent street cocaine use,
- intravenous and/or smoked (crack/ freebase) use,
- positive urine toxicology screen for cocaine,
Inclusion criteria for healthy controls:
- No current, or history of, any DSM-IV diagnosis
- No first-degree relative with history of psychotic, mood, or anxiety disorder
Exclusion Criteria:
- medical contraindications to AMPT administration (e.g., known sensitivity/reaction to AMPT);
- medical contraindications to MPH administration (e.g., history of cardiac problems, seizures, etc.)
- drug or alcohol dependence (except nicotine),
- a primary major DSM-IV psychiatric diagnosis (schizophrenia, bipolar disorder, etc.), unrelated to cocaine or pathological gambling
- positive answers on the cardiac screening questionnaire that may place the subject at higher risk, as determined by cardiologist review of both the questionnaire responses and screening ECG
- current use of psychotropic and/or potentially psychoactive prescription medication,
- physical or laboratory (B-HCG) evidence of pregnancy,
- clotting disorders or recent anticoagulant therapy,
- MRI-incompatible implants and other contraindications for MRI (i.e., aneurysm clip, metal fragments, internal electrical devices such as a cochlear implant, spinal cord stimulator or pacemaker),
- history of claustrophobia or feeling of inability to lie still on his back for the PET or MRI scans,
- history of prior radiation exposure for research purposes within the past year such that participation in this study would place them over Radioactive Drug Research Committee (RDRC) limits for annual radiation exposure. This guideline is an effective dose of 5 rem received per year.
- donation or loss of 550 mL of blood or more (including plasmapheresis) or receipt of a transfusion of any blood product within 8 weeks prior to the first dose of study drug.
- use any prescription medications and/or over-the-counter medications, vitamins and/or herbal supplements within 2 weeks prior to study and for the duration of the study without approval from the study doctor.
- eat grapefruit or grapefruit products, and drink alcohol, and anything containing caffeine 3 days before study and during study
- For CD subjects, < 1 year of cocaine dependence, .
- Subjects with current, past, or anticipated exposure to radiation in the workplace.
Study Plan
This section provides details of the study plan, including how the study is designed and what the study is measuring.
How is the study designed?
Design Details
- Primary Purpose: Other
- Allocation: Non-Randomized
- Interventional Model: Factorial Assignment
- Masking: None (Open Label)
Arms and Interventions
Participant Group / Arm |
Intervention / Treatment |
---|---|
Experimental: Baseline
Subjects will receive 2 baseline PET scans with the radioligands (11C)(+)PHNO and (11C)(+)raclopride
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|
Experimental: Dopamine Release
Subjects will receive 1 PET scan following a PO dose of 60mg of methylphenidate to facilitate dopamine release with the radioligand (11C)(+)PHNO
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|
Experimental: Endogenous Dopamine
Subjects will receive 2 PET scans following 48 hours of dopamine depletion via AMPT with the radioligands (11C)(+)PHNO and (11C)(+)raclopride
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What is the study measuring?
Primary Outcome Measures
Outcome Measure |
Measure Description |
Time Frame |
---|---|---|
BPND
Time Frame: 2 weeks
|
BPND is a measure of dopamine receptor availability
|
2 weeks
|
Collaborators and Investigators
This is where you will find people and organizations involved with this study.
Sponsor
Investigators
- Principal Investigator: Robert Malison, MD, Yale University
Study record dates
These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.
Study Major Dates
Study Start
May 1, 2014
Primary Completion (Actual)
June 9, 2014
Study Completion (Actual)
June 9, 2014
Study Registration Dates
First Submitted
May 20, 2014
First Submitted That Met QC Criteria
May 28, 2014
First Posted (Estimate)
June 2, 2014
Study Record Updates
Last Update Posted (Actual)
February 16, 2023
Last Update Submitted That Met QC Criteria
February 14, 2023
Last Verified
February 1, 2023
More Information
Terms related to this study
Additional Relevant MeSH Terms
- Mental Disorders
- Chemically-Induced Disorders
- Substance-Related Disorders
- Cocaine-Related Disorders
- Physiological Effects of Drugs
- Neurotransmitter Agents
- Molecular Mechanisms of Pharmacological Action
- Central Nervous System Depressants
- Enzyme Inhibitors
- Antipsychotic Agents
- Tranquilizing Agents
- Psychotropic Drugs
- Neurotransmitter Uptake Inhibitors
- Membrane Transport Modulators
- Dopamine Agents
- Dopamine Antagonists
- Dopamine Uptake Inhibitors
- Central Nervous System Stimulants
- Methylphenidate
- Raclopride
- alpha-Methyltyrosine
Other Study ID Numbers
- 1403013567
This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.
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