Effects of Vigabatrin on Cocaine Self-Administration

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

Study Overview

• Status: Terminated
• Conditions: Cocaine Dependence
• Intervention / Treatment: Drug: Vigabatrin; Drug: Cocaine

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 Type: Interventional
• Enrollment (Actual): 1
• Phase: Phase 2

Contacts and Locations

Study Locations

• United States
  • New York
    • New York, New York, United States, 10032
      • Irving Center for Clinical Research

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 21 years to 45 years (Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

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

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Double

Number of Arms

2

Arms and Interventions

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

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Subjective effects
Cardiovascular effects
Cravings
Cocaine Administration

Collaborators and Investigators

• Sponsor: New York State Psychiatric Institute
• Collaborators: Novel Cocaine Pharmacotherapies

Study record dates

Study Major Dates

• Study Start: April 1, 2006
• Primary Completion (Actual): December 1, 2006
• Study Completion (Actual): December 1, 2006

Study Registration Dates

• First Submitted: September 7, 2006
• First Submitted That Met QC Criteria: September 7, 2006
• First Posted (Estimate): September 8, 2006

Study Record Updates

• Last Update Posted (Estimate): October 27, 2016
• Last Update Submitted That Met QC Criteria: October 25, 2016
• Last Verified: October 1, 2016

More Information

Terms related to this study

• Keywords: Vigabatrin; GABA levels; Smoked cocaine
• 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; Peripheral Nervous System Agents; Enzyme Inhibitors; Sensory System Agents; Anesthetics; Neurotransmitter Uptake Inhibitors; Membrane Transport Modulators; Dopamine Agents; GABA Agents; Anticonvulsants; Anesthetics, Local; Dopamine Uptake Inhibitors; Vasoconstrictor Agents; Vigabatrin; Cocaine
• Other Study ID Numbers: 5096; DA 10755 (Other Grant/Funding Number: Novel Cocaine Pharmacotherapies)

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: No