Official Title: “Disulfiram for Cocaine Abuse in Methadone Patients”

This competitive renewal examines further the influence of dopamine beta-hydroxylase enzyme activity on the clinical efficacy of the novel pharmacotherapy, disulfiram, for treating cocaine dependence in 160 cocaine-dependent patients, some of whom are opioid dependent and maintained on an FDA-approved opioid agonist. Cocaine dependent as well as co-morbid cocaine dependence in opioid-dependent individuals is associated with more public health issues and poorer treatment prognosis when admitted to methadone maintenance. However, to date, no effective pharmacotherapies have been developed to treat cocaine dependence. 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 160 cocaine-dependent opioid addicts, aged 18-65 years. Participants 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 one of the following: placebo disulfiram (0 mg/day), disulfiram at 250 mg/day, disulfiram at 375 mg/day, or disulfiram at 500 mg/day. During induction onto methadone or buprenorphine for opioid dependent individuals, participants are administered increasing doses of opioid agonist on a daily basis until maintenance doses of opioid agonist are attained. At the beginning of week 3, participants receive opioid agonist, 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.

Study Type: Interventional

Study Design: Treatment, Randomized, Double Blind (Subject, Caregiver, Investigator), Placebo Control, Parallel Assignment, Efficacy Study

Study Primary Completion Date: April 2011

Intervention(s) in this Clinical Trial

• Drug: Disulfiram
  • Disulfiram at 0, 250, 375, or 500 mg/day for 12 weeks

Arms, Groups and Cohorts in this Clinical Trial

• Placebo Comparator: 1
  • microcrystalline cellulose
• Experimental: 2
  • disulfiram at 250 mg/day
• Experimental: 3
  • Disulfiram at 375 mg/day
• Experimental: 4
  • Disulfiram at 500 mg/day

Primary Measures

• cocaine use as determined by urine toxicology screens
  • Time Frame: 14 weeks
    Safety Issue?: No

Secondary Measures

• retention
  • Time Frame: 14 weeks
    Safety Issue?: No
• disulfiram side-effects profile
  • Time Frame: 14 weeks
    Safety Issue?: Yes
• reductions in self-reported cocaine and other drug or alcohol use
  • Time Frame: 14 weeks
    Safety Issue?: No
• other illicit drug use as assessed by urine toxicology screens
  • Time Frame: 14 weeks
    Safety Issue?: No
• improvements in mood and psychosocial functioning
  • Time Frame: 14 weeks
    Safety Issue?: Yes
• genotype at the DBH locus
  • Time Frame: week 1-2
    Safety Issue?: No
• DβH enzyme activity
  • Time Frame: weeks 1-2 and 6
    Safety Issue?: No

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.

Gender Eligibility for this Clinical Trial: Both

Minimum Age for this Clinical Trial: 18 Years

Maximum Age for this Clinical Trial: 65 Years

Are Healthy Volunteers Accepted for this Clinical Trial?: Accepts Healthy Volunteers

Lead Sponsor: National Institute on Drug Abuse (NIDA)

Overall Clinical Trial Officials and Contacts

Alison Oliveto, Ph.D. Principal Investigator University of Arkansas  

Overall Contact: Amy Glenn, BA 501-526-7969 ALGlenn@uams.edu

Information obtained from ClinicalTrials.gov on October 10, 2008

Link to the current ClinicalTrials.gov record. http://clinicaltrials.gov/show/NCT00395850

Study ID Number: NIDA-13441

ClinicalTrials.gov Identifier: NCT00395850

Health Authority: United States: Food and Drug Administration