Clinical trial NCT00395850: Disulfiram for Cocaine Abuse
Official title: Disulfiram for Cocaine Abuse
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE2
Conditions: Cocaine Dependence
Keywords: cocaine dependence
disulfiram
clinical trial
methadone maintenance
pharmacogenetics
dopamine beta-hydroxylase
Lead sponsor: University of Arkansas
Sponsor class: OTHER
Collaborators: name: National Institute on Drug Abuse (NIDA)
First posted: 2006-11-03
Enrollment: 118
Sex: ALL
Minimum age (years): 18
Maximum age (years): 65
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: yes
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief 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.

Primary outcomes:
measure: Cocaine Use Over Time
timeFrame: thrice weekly for 12 weeks
Secondary outcomes:
measure: Retention
timeFrame: 14 weeks
Other outcomes:
Locations:
city: Little Rock
country: United States
facility: University of Arkansas for Medical Sciences
state: Arkansas
Study officials:
affiliation: University of Arkansas
name: Alison Oliveto, Ph.D.
role: PRINCIPAL_INVESTIGATOR
References: