title: A multisite, double-blind, placebo-controlled clinical trial to evaluate the safety and efficacy of vigabatrin for treating cocaine dependence.
abstract: OBJECTIVE
  Cocaine dependence is a significant public health problem, yet no validated pharmacological treatment exists. The potent γ-aminobutyric acid (GABA)ergic medication vigabatrin has previously been shown to be effective in a double-blind single-site study conducted in Mexico.
  
  
  OBJECTIVE
  To evaluate the safety and efficacy of vigabatrin for the treatment of cocaine dependence in a U.S. sample.
  
  
  METHODS
  Multisite, randomized, double-blind, placebo-controlled, 12-week clinical trial with follow-up visits at weeks 13, 16, 20, and 24 in 11 U.S. sites.
  
  
  METHODS
  In total, 186 treatment-seeking participants with cocaine dependence (mean age, 45 years). Approximately 67% were male, and about 60% were of African American race/ethnicity.
  
  
  METHODS
  Participants received twice-daily doses of vigabatrin (total dosage, 3.0 g/d) or matched placebo, plus weekly computerized cognitive behavioral therapy and biweekly individual counseling for 13 weeks. Contingency management encouraged the provision of urine samples.
  
  
  METHODS
  The primary outcome measure was the proportion of participants with cocaine abstinence during the last 2 weeks of the 12-week treatment phase as assessed by self-reports and quantitative urine drug screens. The weekly fraction of cocaine use days and the number of drug-free urine samples during weeks 1 through 13 were key secondary measures.
  
  
  RESULTS
  No significant differences were observed between the vigabatrin group and the placebo group on the primary outcome measure (P = .67), key secondary measures (P > .99), or other outcome measures. However, while pill counts and self-reports indicated that more than 66% of all participants (and >63% of the vigabatrin group) took more than 70% of their medication, post hoc vigabatrin urine concentration levels suggested that approximately 40% to 60% of patients taking vigabatrin may not have been adherent. This lack of adherence may have obscured any evidence of vigabatrin efficacy. No visual acuity or visual field deterioration occurred in any of the participants.
  
  
  CONCLUSIONS
  No protocol-defined differences in efficacy between vigabatrin treatment and placebo were detected for any outcome variable. This may have been due to medication nonadherence or, alternatively, due to the weak efficacy of vigabatrin.
  
  
  BACKGROUND
  clinicaltrials.gov Identifier: NCT00611130.
authors.affiliation: Department of Veterans Affairs Medical Center, University of Cincinnati College of Medicine, USA. somoza@carc.uc.edu
authors.forename: Eugene C
authors.initials: EC
authors.lastname: Somoza
authors.forename: Douglas
authors.initials: D
authors.lastname: Winship
authors.forename: Charles W
authors.initials: CW
authors.lastname: Gorodetzky
authors.forename: Daniel
authors.initials: D
authors.lastname: Lewis
authors.forename: Domenic A
authors.initials: DA
authors.lastname: Ciraulo
authors.forename: Gantt P
authors.initials: GP
authors.lastname: Galloway
authors.forename: Scott D
authors.initials: SD
authors.lastname: Segal
authors.forename: Michael
authors.initials: M
authors.lastname: Sheehan
authors.forename: John D
authors.initials: JD
authors.lastname: Roache
authors.forename: Warren K
authors.initials: WK
authors.lastname: Bickel
authors.forename: Donald
authors.initials: D
authors.lastname: Jasinski
authors.forename: Donnie W
authors.initials: DW
authors.lastname: Watson
authors.forename: Steven R
authors.initials: SR
authors.lastname: Miller
authors.forename: Peggy
authors.initials: P
authors.lastname: Somoza
authors.forename: Theresa
authors.initials: T
authors.lastname: Winhusen
mesh_terms: D000328:Adult; D003042:Cocaine / Q000031:analogs & derivatives / Q000652:urine; D019970:Cocaine-Related Disorders / Q000188:drug therapy*; D004311:Double-Blind Method; D005260:Female; D018682:GABA Agents / Q000009:adverse effects / Q000627:therapeutic use*; D006801:Humans; D008297:Male; D055118:Medication Adherence; D008875:Middle Aged; D016896:Treatment Outcome; D020888:Vigabatrin / Q000009:adverse effects / Q000627:therapeutic use*
chemical_list: D018682:GABA Agents; C005618:benzoylecgonine; D020888:Vigabatrin; D003042:Cocaine