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

Primary Purpose

Cocaine Dependence

Status
Terminated
Phase
Not Applicable
Locations
United States
Study Type
Interventional
Intervention
Methylphenidate
Alpha Methyl Para Tyrosine (AMPT)
[11C]PHNO
[11C]raclopride
Sponsored by
Yale University
About
Eligibility
Locations
Arms
Outcomes
Full info

About this trial

This is an interventional other trial for Cocaine Dependence

Eligibility Criteria

18 Years - 50 Years (Adult)All SexesAccepts Healthy Volunteers

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.

Sites / Locations

  • Connecticut Mental Health Center

Arms of the Study

Arm 1

Arm 2

Arm 3

Arm Type

Experimental

Experimental

Experimental

Arm Label

Baseline

Dopamine Release

Endogenous Dopamine

Arm Description

Subjects will receive 2 baseline PET scans with the radioligands (11C)(+)PHNO and (11C)(+)raclopride

Subjects will receive 1 PET scan following a PO dose of 60mg of methylphenidate to facilitate dopamine release with the radioligand (11C)(+)PHNO

Subjects will receive 2 PET scans following 48 hours of dopamine depletion via AMPT with the radioligands (11C)(+)PHNO and (11C)(+)raclopride

Outcomes

Primary Outcome Measures

BPND
BPND is a measure of dopamine receptor availability

Secondary Outcome Measures

Full Information

First Posted
May 20, 2014
Last Updated
February 14, 2023
Sponsor
Yale University
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1. Study Identification

Unique Protocol Identification Number
NCT02152670
Brief Title
Understanding Dopamine Mechanisms in Cocaine Addiction Using AMPT and Methylphenidate With [11C]RAC/[11C]PHNO PET
Study Type
Interventional

2. Study Status

Record Verification Date
February 2023
Overall Recruitment Status
Terminated
Why Stopped
Study drug became unaffordable for the purposes of the research.
Study Start Date
May 2014 (undefined)
Primary Completion Date
June 9, 2014 (Actual)
Study Completion Date
June 9, 2014 (Actual)

3. Sponsor/Collaborators

Responsible Party, by Official Title
Sponsor
Name of the Sponsor
Yale University

4. Oversight

Data Monitoring Committee
Yes

5. Study Description

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.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Cocaine Dependence

7. Study Design

Primary Purpose
Other
Study Phase
Not Applicable
Interventional Study Model
Factorial Assignment
Masking
None (Open Label)
Allocation
Non-Randomized
Enrollment
1 (Actual)

8. Arms, Groups, and Interventions

Arm Title
Baseline
Arm Type
Experimental
Arm Description
Subjects will receive 2 baseline PET scans with the radioligands (11C)(+)PHNO and (11C)(+)raclopride
Arm Title
Dopamine Release
Arm Type
Experimental
Arm Description
Subjects will receive 1 PET scan following a PO dose of 60mg of methylphenidate to facilitate dopamine release with the radioligand (11C)(+)PHNO
Arm Title
Endogenous Dopamine
Arm Type
Experimental
Arm Description
Subjects will receive 2 PET scans following 48 hours of dopamine depletion via AMPT with the radioligands (11C)(+)PHNO and (11C)(+)raclopride
Intervention Type
Drug
Intervention Name(s)
Methylphenidate
Intervention Type
Drug
Intervention Name(s)
Alpha Methyl Para Tyrosine (AMPT)
Intervention Type
Other
Intervention Name(s)
[11C]PHNO
Intervention Type
Other
Intervention Name(s)
[11C]raclopride
Primary Outcome Measure Information:
Title
BPND
Description
BPND is a measure of dopamine receptor availability
Time Frame
2 weeks

10. Eligibility

Sex
All
Minimum Age & Unit of Time
18 Years
Maximum Age & Unit of Time
50 Years
Accepts Healthy Volunteers
Accepts Healthy Volunteers
Eligibility Criteria
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.
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Robert Malison, MD
Organizational Affiliation
Yale University
Official's Role
Principal Investigator
Facility Information:
Facility Name
Connecticut Mental Health Center
City
New Haven
State/Province
Connecticut
ZIP/Postal Code
06519
Country
United States

12. IPD Sharing Statement

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

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