Clinical trial NCT00611130: Vigabatrin for Treatment of Cocaine Dependence
Official title: Vigabatrin for Treatment of Cocaine Dependence: A Phase II Study
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE2
Conditions: Cocaine Dependence
Keywords: Cocaine
Addiction
Dependence
Treatment
Lead sponsor: Catalyst Pharmaceuticals, Inc.
Sponsor class: INDUSTRY
First posted: 2008-02-08
Enrollment: 186
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief summary: The objective of this study is to demonstrate that a larger proportion of vigabatrin-treated subjects than placebo-treated subjects will be cocaine-free in the last 2 weeks of treatment.

Detailed description: Cocaine addiction, a serious public health concern associated with significant medical, social, and economic consequences, is difficult to treat using traditional psychosocial and behavioral therapies. Despite testing of a number of different agents for cocaine dependency, there remains no proven pharmacologic treatment for cocaine addiction.

The addictive properties of cocaine have been associated with its actions on mesotelencephalic dopamine reward pathways in the central nervous system (CNS). Cocaine administration increases the levels of dopamine, a neurotransmitter associated with sensations of pleasure and reward. Therefore, blocking cocaine-induced increases in dopamine levels represents a valid pharmaceutical approach to the treatment of cocaine addiction.

Another neurotransmitter, gamma-aminobutyric acid (GABA), suppresses striatal dopamine release, and attenuates cocaine-induced increases in extracellular and synaptic dopamine levels in the striatum and nucleus accumbens in animal models of drug dependence. Significant elevation of brain GABA levels may reduce cocaine-stimulated dopamine release and dampen the sensations of pleasure and reward. Thus, drugs that potentiate or enhance GABA-ergic transmission are candidates for the treatment of cocaine addiction.

Eligibility criteria: Inclusion Criteria:

* Able to understand the study and provide written informed consent.
* Male or female at least 18 years of age.
* Meets DSM-IV (Diagnostic and Statistical Manual of Mental Disorders Fourth Edition) criteria for cocaine dependence as primary diagnosis, as determined by the Substance Abuse module of SCID (Structured Clinical Interview for DSM-IV).
* Provide at least one urine sample that is positive for cocaine according to a rapid screening test.
* Seeking treatment for cocaine dependence.
* Have normal visual fields.
* Be in generally good health based on history, physical examination, electrocardiogram and laboratory findings.
* If female of childbearing potential, use acceptable contraceptive methods. (oral contraceptives (the pill), IUDs, contraceptive implants under the skin, contraceptive rings or patches or injections, diaphragms with spermicide, and condoms with spermicide). Surgical sterilization by tubal ligation or hysterectomy is acceptable

Exclusion Criteria:

* Has current dependence, as determined by the SCID, on any psychoactive substance other than cocaine, alcohol, nicotine, or marijuana or physiologic dependence on alcohol requiring medical detoxification.
* Has any serious medical or psychiatric illness and/or clinically significant abnormal laboratory value, which in the judgment of the Principal Investigator or his/her designee would make study participation unsafe, or would make treatment compliance difficult or put the study staff at undue risk.
* Be under court mandate to obtain treatment.
* Be enrolled in an opiate substitution treatment program within 2 months of randomization.
* Has ever taken vigabatrin in the past.
* Is pregnant or lactating.
* Has clinically significant ophthalmologic disease, which would preclude safety monitoring or is undergoing treatment for ocular disease.
* Has received a drug with known major organ toxicity, including retinotoxicity within 30 days of randomization.
* Is currently participating in, or has been enrolled in another clinical trial within the last 30 days.
* Be anyone who, in the judgment of the investigator, would not be expected to attend regular study visits or to complete the study protocol, due to imminent relocation from the clinic area, legal difficulties, work-related problems, transportation, etc.

Primary outcomes:
measure: Proportion of Subjects in Each Treatment Group Abstinent During the Last 2 Weeks of Treatment.
timeFrame: Week 13
Secondary outcomes:
Other outcomes:
Locations:
city: Little Rock
country: United States
facility: Addiction Treatment Clinic
state: Arkansas
city: San Francisco
country: United States
facility: St. Luke's Hospital Addiction Pharmacology Research Laboratory
state: California
city: Torrance
country: United States
facility: Friends Research Institute
state: California
city: Largo
country: United States
facility: Operation PAR
state: Florida
city: North Miami
country: United States
facility: Segal Institute for Clinical Research
state: Florida
city: Baltimore
country: United States
facility: Johns Hopkins Bayview Medical Center Center for Chemical Dependence
state: Maryland
city: Boston
country: United States
facility: Boston University School of Medicine
state: Massachusetts
city: New York
country: United States
facility: New York University Mental Health and Addictive Disorders Research Program
state: New York
city: Cincinnati
country: United States
facility: Cincinnati Addiction Research Center (CinARC)
state: Ohio
city: Dayton
country: United States
facility: Dayton Veterans Affairs Medical Center
state: Ohio
city: San Antonio
country: United States
facility: University of Texas Health Science Center at San Antonio
state: Texas
Study officials:
affiliation: University of Cincinnati
name: Eugene Somoza, MD, PhD
role: PRINCIPAL_INVESTIGATOR
References:
citation: Somoza EC, Winship D, Gorodetzky CW, Lewis D, Ciraulo DA, Galloway GP, Segal SD, Sheehan M, Roache JD, Bickel WK, Jasinski D, Watson DW, Miller SR, Somoza P, Winhusen T. A multisite, double-blind, placebo-controlled clinical trial to evaluate the safety and efficacy of vigabatrin for treating cocaine dependence. JAMA Psychiatry. 2013 Jun;70(6):630-7. doi: 10.1001/jamapsychiatry.2013.872.
citation: Berezina TL, Khouri AS, Winship MD, Fechtner RD. Visual field and ocular safety during short-term vigabatrin treatment in cocaine abusers. Am J Ophthalmol. 2012 Aug;154(2):326-332.e2. doi: 10.1016/j.ajo.2012.02.026. Epub 2012 Jun 15.