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Understanding Dopamine Mechanisms in Cocaine Addiction Using AMPT and Methylphenidate With [11C]RAC/[11C]PHNO PET

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details.
 
ClinicalTrials.gov Identifier: NCT02152670
Recruitment Status : Active, not recruiting
First Posted : June 2, 2014
Last Update Posted : December 6, 2019
Sponsor:
Information provided by (Responsible Party):
Yale University

Tracking Information
First Submitted Date  ICMJE May 20, 2014
First Posted Date  ICMJE June 2, 2014
Last Update Posted Date December 6, 2019
Study Start Date  ICMJE May 2014
Estimated Primary Completion Date May 2021   (Final data collection date for primary outcome measure)
Current Primary Outcome Measures  ICMJE
 (submitted: May 28, 2014)
BPND [ Time Frame: 2 weeks ]
BPND is a measure of dopamine receptor availability
Original Primary Outcome Measures  ICMJE Same as current
Change History Complete list of historical versions of study NCT02152670 on ClinicalTrials.gov Archive Site
Current Secondary Outcome Measures  ICMJE Not Provided
Original Secondary Outcome Measures  ICMJE Not Provided
Current Other Pre-specified Outcome Measures Not Provided
Original Other Pre-specified Outcome Measures Not Provided
 
Descriptive Information
Brief Title  ICMJE Understanding Dopamine Mechanisms in Cocaine Addiction Using AMPT and Methylphenidate With [11C]RAC/[11C]PHNO PET
Official Title  ICMJE Not Provided
Brief Summary 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.
Detailed Description Not Provided
Study Type  ICMJE Interventional
Study Phase  ICMJE Not Applicable
Study Design  ICMJE Allocation: Non-Randomized
Intervention Model: Factorial Assignment
Masking: None (Open Label)
Primary Purpose: Other
Condition  ICMJE Cocaine Dependence
Intervention  ICMJE
  • Drug: Methylphenidate
  • Drug: Alpha Methyl Para Tyrosine (AMPT)
  • Other: [11C]PHNO
  • Other: [11C]raclopride
Study Arms  ICMJE
  • Experimental: Baseline
    Subjects will receive 2 baseline PET scans with the radioligands (11C)(+)PHNO and (11C)(+)raclopride
    Interventions:
    • Other: [11C]PHNO
    • Other: [11C]raclopride
  • 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
    Interventions:
    • Drug: Methylphenidate
    • Other: [11C]PHNO
  • 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
    Interventions:
    • Drug: Alpha Methyl Para Tyrosine (AMPT)
    • Other: [11C]PHNO
    • Other: [11C]raclopride
Publications * Not Provided

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Recruitment Information
Recruitment Status  ICMJE Active, not recruiting
Estimated Enrollment  ICMJE
 (submitted: May 28, 2014)
48
Original Estimated Enrollment  ICMJE Same as current
Estimated Study Completion Date  ICMJE May 2021
Estimated Primary Completion Date May 2021   (Final data collection date for primary outcome measure)
Eligibility Criteria  ICMJE

Inclusion Criteria:

  1. age 18 - 50 years,
  2. voluntary, written, informed consent,
  3. physically healthy by medical history, physical, neurological, ECG, and laboratory examinations,
  4. 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.
  5. English speaking
  6. No other major Axis DSM-IV diagnosis present, besides required as below

Inclusion criteria for cocaine dependent:

  1. DSM-IV criteria for Cocaine Abuse (305.60) or Cocaine Dependence (304.20)
  2. recent street cocaine use,
  3. intravenous and/or smoked (crack/ freebase) use,
  4. positive urine toxicology screen for cocaine,

Inclusion criteria for healthy controls:

  1. No current, or history of, any DSM-IV diagnosis
  2. No first-degree relative with history of psychotic, mood, or anxiety disorder

Exclusion Criteria:

  1. medical contraindications to AMPT administration (e.g., known sensitivity/reaction to AMPT);
  2. medical contraindications to MPH administration (e.g., history of cardiac problems, seizures, etc.)
  3. drug or alcohol dependence (except nicotine),
  4. a primary major DSM-IV psychiatric diagnosis (schizophrenia, bipolar disorder, etc.), unrelated to cocaine or pathological gambling
  5. 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
  6. current use of psychotropic and/or potentially psychoactive prescription medication,
  7. physical or laboratory (B-HCG) evidence of pregnancy,
  8. clotting disorders or recent anticoagulant therapy,
  9. 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),
  10. history of claustrophobia or feeling of inability to lie still on his back for the PET or MRI scans,
  11. 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.
  12. 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.
  13. 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.
  14. eat grapefruit or grapefruit products, and drink alcohol, and anything containing caffeine 3 days before study and during study
  15. For CD subjects, < 1 year of cocaine dependence, .
  16. Subjects with current, past, or anticipated exposure to radiation in the workplace.
Sex/Gender  ICMJE
Sexes Eligible for Study: All
Ages  ICMJE 18 Years to 50 Years   (Adult)
Accepts Healthy Volunteers  ICMJE Yes
Contacts  ICMJE Contact information is only displayed when the study is recruiting subjects
Listed Location Countries  ICMJE United States
Removed Location Countries  
 
Administrative Information
NCT Number  ICMJE NCT02152670
Other Study ID Numbers  ICMJE 1403013567
Has Data Monitoring Committee Yes
U.S. FDA-regulated Product Not Provided
IPD Sharing Statement  ICMJE Not Provided
Responsible Party Yale University
Study Sponsor  ICMJE Yale University
Collaborators  ICMJE Not Provided
Investigators  ICMJE
Principal Investigator: Robert Malison, MD Yale University
PRS Account Yale University
Verification Date December 2019

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP