Disulfiram for Cocaine Abuse
Condition: Cocaine Dependence
MeSH terms: Cocaine-Related Disorders
Intervention: Disulfiram
Intervention description: Disulfiram at 0, 250, 375, or 500 mg/day for 12 weeks
Intervention MeSH terms: Disulfiram
Phase: Phase 2
Study type: Interventional
Primary purpose: Treatment
Allocation: Randomized
Intervention model: Parallel Assignment
Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
Enrollment: 118.0
Sex: All
Minimum age: 18 Years
Maximum age: 65 Years
Healthy volunteers: Accepts Healthy Volunteers
Keywords: cocaine dependence; disulfiram; clinical trial; methadone maintenance; pharmacogenetics; dopamine beta-hydroxylase

Summary:

      This study examines the influence of dopamine beta-hydroxylase enzyme activity on the
      clinical efficacy of the novel pharmacotherapy, disulfiram, for treating cocaine dependence
      in cocaine-dependent patients, some of whom are opioid dependent and maintained on an
      FDA-approved opioid agonist. Cocaine dependence as well as co-morbid cocaine and
      opioid-dependence is associated with more public health issues and poorer treatment prognosis
      when admitted to methadone maintenance. Yet no effective pharmacotherapies have been
      developed to treat cocaine dependence to date. One novel pharmacotherapy, disulfiram, has
      shown some promise as a treatment for this disorder in several clinical trials at a dose of
      250 mg/day or more (e.g., Carroll et al., 1998, 2004). This 14-week, randomized, double blind
      clinical trial will provide treatment for up to160 cocaine-dependent individuals, aged 18-65
      years. Participants who are opioid dependent will be stabilized on methadone maintenance
      during the first 2 weeks and baseline cocaine use will be assessed; participants will be
      stratified by DBH genotype and randomly assigned to receive disulfiram at either 0, 250, 375
      or 500 mg/day. During induction onto methadone for opioid dependent individuals, participants
      are administered increasing doses of methadone on a daily basis until maintenance doses are
      attained. At the beginning of week 3, participants receive methadone, if relevant, plus
      disulfiram or placebo disulfiram according to their randomized assignments, and are
      maintained on study medication(s) through week 14. At the end of the study, participants will
      undergo detoxification from the opioid agonist, if relevant, and active/placebo medication
      over a 4- to 6-week period. All participants receive weekly 1-hour psychotherapy (Cognitive
      Behavioral Treatment) with experienced clinicians specifically trained to deliver the therapy
      and who will receive ongoing supervision. Participants undergo a delay discounting session
      during week 1. The primary outcomes will be retention, reduction in opioid and cocaine use,
      as assessed by self-report and confirmed by thrice-weekly urinalyses, and disulfiram
      side-effects profile. Secondary outcomes will include reductions in other illicit drug and
      alcohol use, and improvements in psychosocial functioning. The prognostic relevance of
      genotype at the DBH locus, DβH activity, etc., on response to disulfiram will be examined.
    

Eligibility criteria:

        Inclusion Criteria:

          -  current users of cocaine, including having a cocaine-positive urine

          -  self-reported use of > 7 gm during the preceding 6 months and > 1 time/week in at
             least one month preceding study entry

          -  meet DSM-IV criteria for cocaine dependence

        Exclusion Criteria:

          -  current diagnosis of alcohol dependence

          -  significant medical conditions such as abnormal liver function

          -  active hepatitis

          -  hypertension

          -  a current cardiac condition or high risk of cardiovascular disease

          -  seizure disorders

          -  any another significant underlying medical condition which would contraindicate
             disulfiram or methadone treatment

          -  meeting DSM-IV psychiatric classifications for schizophrenia, bipolar disorder, or
             other psychotic disorders

          -  exhibiting current suicidality or homicidality

          -  pregnancy

          -  current use of a prescribed psychotropic medication (e.g., antidepressants,
             anxiolytics, antipsychotics, anticonvulsants, etc.) which cannot be discontinued
             current use of medications such as anticoagulants, isoniazid, metronidazole,
             clotrimazole, and paraldehyde.