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

• Sponsor: Yale University (Other)
• Overall Status: Terminated
• CT.gov ID: NCT02152670
• Collaborator: (none)
• Enrollment: 1
• Location: 1
• Arms: 3
• Duration (Months): 1.3
• Patients Per Site Per Month: 0.8

Study Details

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.

Condition or Disease	Intervention/Treatment	Phase
Cocaine Dependence	Drug: Methylphenidate; Drug: Alpha Methyl Para Tyrosine (AMPT); Other: [11C]PHNO; Other: [11C]raclopride	N/A

Study Design

• Study Type: Interventional
• Actual Enrollment: 1 participants
• Allocation: Non-Randomized
• Intervention Model: Factorial Assignment
• Masking: None (Open Label)
• Primary Purpose: Other
• Study Start Date: May 1, 2014
• Actual Primary Completion Date: Jun 9, 2014
• Actual Study Completion Date: Jun 9, 2014

Arms and Interventions

Arm	Intervention/Treatment
Experimental: Baseline Subjects will receive 2 baseline PET scans with the radioligands (11C)(+)PHNO and (11C)(+)raclopride	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	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	Drug: Alpha Methyl Para Tyrosine (AMPT); Other: [11C]PHNO; Other: [11C]raclopride

Outcome Measures

Primary Outcome Measures

1. BPND [2 weeks]

   BPND is a measure of dopamine receptor availability

Eligibility Criteria

Criteria

• Ages Eligible for Study: 18 Years to 50 Years
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: Yes

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.

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	Connecticut Mental Health Center	New Haven	Connecticut	United States	06519

Sponsors and Collaborators

• Yale University

Investigators

• Principal Investigator: Robert Malison, MD, Yale University

Study Documents (Full-Text)

None provided.

More Information

Publications

None provided.

• Responsible Party: Yale University
• ClinicalTrials.gov Identifier: NCT02152670
• Other Study ID Numbers: 1403013567
• First Posted: Jun 2, 2014
• Last Update Posted: Feb 25, 2021
• Last Verified: Feb 1, 2021

• Additional relevant MeSH terms: Cocaine-Related Disorders; Raclopride; Methylphenidate; alpha-Methyltyrosine

Study Results

Participant Flow

Arm/Group Title	Enrolled and Randomized
Arm/Group Description	This summarizes the single patient enrolled and randomized to the study.
Period Title: Overall Study
STARTED	1
COMPLETED	1
NOT COMPLETED	0

Baseline Characteristics

Arm/Group Title	Enrolled and Randomized
Arm/Group Description	This summarizes the single patient enrolled and randomized to the study.
Overall Participants	0
Age () []
<=18 years
Between 18 and 65 years
>=65 years
Age () []
Sex: Female, Male () []
Female
Male
Race (NIH/OMB) () []
American Indian or Alaska Native
Asian
Native Hawaiian or Other Pacific Islander
Black or African American
White
More than one race
Unknown or Not Reported
Region of Enrollment (participants) []

Outcome Measures

1. Primary Outcome

Title	BPND
Description	BPND is a measure of dopamine receptor availability
Time Frame	2 weeks

Outcome Measure Data

Analysis Population Description

Only a single patient was enrolled and randomized.

Arm/Group Title	Enrolled and Randomized
Arm/Group Description	This summarizes the single patient enrolled and randomized to the study.
Measure Participants	0

Adverse Events

Time Frame	2 weeks
Arm/Group Title	Enrolled and Randomized
Arm/Group Description	This summarizes the single patient enrolled and randomized to the study.
All Cause Mortality
	Enrolled and Randomized
	Affected / at Risk (%)	# Events
Total	0/1 (0%)
Serious Adverse Events
	Enrolled and Randomized
	Affected / at Risk (%)	# Events
Total	0/1 (0%)
Other (Not Including Serious) Adverse Events
	Enrolled and Randomized
	Affected / at Risk (%)	# Events
Total	0/1 (0%)

Limitations/Caveats

[Not Specified]

More Information

Certain Agreements

All Principal Investigators ARE employed by the organization sponsoring the study.

There is NOT an agreement between Principal Investigators and the Sponsor (or its agents) that restricts the PI's rights to discuss or publish trial results after the trial is completed.