Effects of Vigabatrin on Cocaine Self-Administration

Sponsor

New York State Psychiatric Institute (Other)

Overall Status

Terminated

CT.gov ID

NCT00373581

Collaborator

Novel Cocaine Pharmacotherapies (Other)

Enrollment

Location

Arms

Duration (Months)

0.1

Patients Per Site Per Month

Study Details

Study Description

Brief Summary

The objective of this study is to determine if vigabatrin will decrease cocaine self-administration, cardiovascular effects, subjective effects and craving compared to placebo.

Condition or Disease	Intervention/Treatment	Phase
Cocaine Dependence	Drug: Vigabatrin Drug: Cocaine	Phase 2

Detailed Description

Two recent open label clinical trials have reported that the anticonvulsant, gamma vinyl-GABA (GVG; vigabatrin), decreases relapse to cocaine use (Brodie et al., 2003, 2005). Vigabatrin increases neural GABA levels by irreversibly inhibiting the primary GABA degradation enzyme, GABA-transaminase; the hypothesized mechanism by which vigabatrin decreases cocaine relapse is by increasing GABA levels, thereby decreasing the effects of cocaine and cocaine-associated environmental cues on extracellular dopamine concentrations in the mesolimbic dopaminergic pathway (Morgan and Dewey, 1998). We are proposing to use our model of repeated dose cocaine self-administration to assess the interaction between vigabatrin and smoked cocaine under controlled laboratory conditions. This 57-day outpatient/inpatient /outpatient/inpatient protocol will evaluate the effects of vigabatrin maintenance (0, 3 g/day) on cocaine craving, subjective effects, and self-administration using a within-subjects design. Non-treatment seeking cocaine-dependent volunteers will be maintained outpatient for 14 days of vigabatrin maintenance prior to beginning each inpatient study phase. During the inpatient phases, volunteers will live on a hospital clinical research unit and will participate in laboratory sessions in which they will have the opportunity to purchase doses of smoked cocaine (0, 12, 25, 50 mg; $5/administration). In addition to measuring cocaine self-administration, we will measure the cardiovascular and subjective effects of repeated cocaine administration and cocaine craving under each vigabatrin maintenance condition. Determining vigabatrin's effects on a range of smoked cocaine doses will provide essential data on the mechanism of the vigabatrin-cocaine interaction.

Study Design

Study Type:

Interventional

Actual Enrollment :

1 participants

Allocation:

Randomized

Intervention Model:

Parallel Assignment

Masking:

Double (Participant, Investigator)

Primary Purpose:

Treatment

Official Title:

Effects of Vigabatrin on Cocaine Self-Administration

Study Start Date :

Apr 1, 2006

Actual Primary Completion Date :

Dec 1, 2006

Actual Study Completion Date :

Dec 1, 2006

Arms and Interventions

Arm	Intervention/Treatment
Experimental: Vigabatrin, cocaine	Drug: Vigabatrin Drug: Cocaine
Placebo Comparator: placebo, cocaine	Drug: Vigabatrin Drug: Cocaine

Arm

Intervention/Treatment

Experimental: Vigabatrin, cocaine

Drug: Vigabatrin

Drug: Cocaine

Placebo Comparator: placebo, cocaine

Drug: Vigabatrin

Drug: Cocaine

Outcome Measures

Primary Outcome Measures

Subjective effects []
Cardiovascular effects []
Cravings []
Cocaine Administration []

Eligibility Criteria

Criteria

Ages Eligible for Study:

21 Years to 45 Years

Sexes Eligible for Study:

All

Accepts Healthy Volunteers:

Yes

Inclusion Criteria:

Meets DSM-IV criteria for current cocaine abuse
Average use of smoked cocaine is at least 2x/week for past 6 mos; currently spends at least $70 per week on cocaine
Has patterns of smoked cocaine use in terms of frequency and amounts which parallel or exceed those administered in the study
Age 21-45
Able to give informed consent, and comply with study procedures
Agrees to practice an effective form of contraception

Exclusion Criteria:

Current seizure disorder or heart disease
Currently meeting DSM-IV criteria for all major psychiatric/psychotic disorders. Volunteers with a history of depression or psychosis will also be excluded (p. 43, Investigator's brochure)
Dependence on substances other than cocaine or nicotine
Request for drug treatment
Judged to be noncompliant with study protocol
Clinical laboratory tests outside normal limits that are unacceptable to the study physician (e.g., BP > 140/90; BUN, creatinine, LFTs > 1.5 ULN; hematocrit < 34 for women, < 36 for men; pseudocholinesterase deficiency)
Current parole or probation
Recent history of significant violent or suicidal behavior
Pregnancy or lactation
Baseline visual field defects