Double Blind Study of Vigabatrin for the Treatment of Cocaine Dependence

• 3 consecutive weeks of negative urines (one slip allowed) [ Time Frame: Last 3 weeks (7,8,9) of the trial ]
• cocaine craving [ Time Frame: Weeks 1, 5,9 ]

• 3 consecutive weeks of negative urines (one slip allowed) [ Time Frame: Last 3 weeks (7,8,9) of the trial ]
• Longest number of consecutive days abstinent, the number of days until onset of 21 consecutive days abstinent, the number of days to relapse after 3 days of abstinence [ Time Frame: Duration of the 9 week trial ]

• Drug: Vigabatrin
  crystalline drug dissolved in orange juice, dosage escalates from 500 mg twice daily to 1.5 g twice daily over a 3 week period. This dose is maintained for 4 weeks and then tapered to zero over the next two weeks
  Other Names:

  • Sabril
  • CPP 109
  • gamma vinyl GABA
  • GVG
• Drug: Placebo
  orange juice is administered twice daily in containers indistinguishable from the treatment arm.
• Behavioral: Group therapy
  Participants attend group sessions once a week

• Active Comparator: A
  Subjects will receive vigabatrin in escalating doses to 3 grams per day over three weeks, continued for 4 weeks and then tapered to zero over the next 2 weeks.
  Interventions:

  • Drug: Vigabatrin
  • Behavioral: Group therapy
• Placebo Comparator: B
  Orange juice and administration identical to Arm A.
  Interventions:

  • Drug: Placebo
  • Behavioral: Group therapy

• Fechtner RD, Khouri AS, Figueroa E, Ramirez M, Federico M, Dewey SL, Brodie JD. Short-term treatment of cocaine and/or methamphetamine abuse with vigabatrin: ocular safety pilot results. Arch Ophthalmol. 2006 Sep;124(9):1257-62.
• Brodie JD, Figueroa E, Laska EM, Dewey SL. Safety and efficacy of gamma-vinyl GABA (GVG) for the treatment of methamphetamine and/or cocaine addiction. Synapse. 2005 Feb;55(2):122-5.
• Brodie JD, Figueroa E, Dewey SL. Treating cocaine addiction: from preclinical to clinical trial experience with gamma-vinyl GABA. Synapse. 2003 Dec 1;50(3):261-5.
• Brodie JD, Case BG, Figueroa E, Dewey SL, Robinson JA, Wanderling JA, Laska EM. Randomized, double-blind, placebo-controlled trial of vigabatrin for the treatment of cocaine dependence in Mexican parolees. Am J Psychiatry. 2009 Nov;166(11):1269-77. doi: 10.1176/appi.ajp.2009.08121811. Epub 2009 Aug 3.

Inclusion Criteria:

In order to participate in the study, subjects must

• Be at least 18 years of age and no older than 55 years of age.
• Weigh more than 100 pounds.
• Have a DSM-IV diagnosis of cocaine dependence.
• Be seeking treatment for cocaine dependence.
• Have a urine sample positive for qualitative cocaine toxicology at initial screening.
• Have the ability to understand, and having understood, provide written informed consent to comply with the treatment protocol.
• Have a history and brief physical examination that demonstrate no clinically significant contraindication for participating in the study, in the judgment of the admitting physician and the Principal Investigator.
• Have normal, or, if necessary, corrected visual acuity, visual fields, and normal fundoscopy findings

Exclusion Criteria:

• In order to participate in the study, subjects must not:

  • Meet DSM-IV criteria for current dependence on any psychoactive substance other than cocaine, alcohol, nicotine, or marijuana or physiological dependence on alcohol requiring medical detoxification.
  • Have neurological or psychiatric disorders such as: psychosis, bipolar illness, major depression, organic brain disease, dementia, any disorder which would require ongoing treatment or which would make study agent compliance difficult, history of suicide attempts assessed and/or current suicidal ideation/plan.
  • Have serious medical illnesses or other potentially life threatening or progressive medical illness other than addiction that may compromise subject safety or study conduct.
  • Have a history of traumatic head injury.
  • Be mandated by a court to obtain treatment for cocaine dependence.
  • Have been treated for cocaine addiction, or abstained from cocaine use for a significant period, within the 6 months preceding screening.
  • Be unable to complete the study protocol because of probable incarceration or relocation from the clinical area.
  • Have AIDS (although AIDS is an exclusion criterion, a positive antibody titer to HIV is not).
  • Have active syphilis that has not been treated or refuse treatment for syphilis
  • Have a history of neuroleptic malignant syndrome.
  • Have known or suspected hypersensitivity to vigabatrin or any other GABAergic drug.
  • Have received a drug with known potential for toxicity to a major organ system within 30 days prior to study entry (e.g., isoniazid, methotrexate).
  • Have participated in any experimental study within 4 weeks, or participated in any clinical trial utilizing vigabatrin.
  • Be pregnant or lactating.
  • Have any clinically significant abnormal laboratory value.
  • Have had electroconvulsive therapy with the 3 months preceding screening.
  • Have had any opiate-substitutes (methadone, LAAM, buprenorphine) within 2 months preceding screening.
  • Have a history of i.v. cocaine (or other psychoactive drug) use within 2 months preceding screening.
  • Have a current or past history of seizure disorder, including alcohol- or stimulant related seizure, febrile seizure, or significant family history of idiopathic seizure disorder.
  • Have a visual field defect, or factor predisposing to visual field defects, including glaucoma, severe myopia, retinal disorder, cataracts, diabetes or uncontrolled hypertension.
  • Have my illness, condition, and use of medications, in the opinion of the Principal Investigator and the admitting physician, which would preclude safe or successful completion of the study.

  • Be using vigabatrin or any medication that could interact adversely with vigabatrin administration, based on the longest time interval of A or B below:

    • A) Five half-lives of other medication or active metabolite(s), whichever is longer;
    • B) Two weeks.
  • Be lactose intolerant.