Disulfiram for Cocaine Abuse

NCT00395850 | Completed Phase 2 Results DMC

• 12 other identifiers: NIDA-134415R01DA013441-025R01DA013441-035R01DA013441-045R01DA013441-061R01DA013441-01A17R01DA013441-055R01DA013441-095R01DA013441-105R01DA013441-08R01DA013441DPMC
• Study Type: interventional
• Target: 118
• Locations: 1 country
• Sites: 1

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.

Conditions

Cocaine Dependence

Keywords

cocaine dependence; disulfiram; clinical trial; methadone maintenance; pharmacogenetics; dopamine beta-hydroxylase

Outcome Measures

Primary Outcomes (1)

• Cocaine Use Over Time

  Urine toxicology results (dichotomous: positive or negative) for the presence of cocaine/cocaine metabolite during the disulfiram phase of the study. The change in the probability of a cocaine positive urine sample per day was assessed for each dose compared with placebo and slopes for each dose condition were calculated from Repeated Measures Genearlized Linear Models on a Binomial distribution (thus a Repeated Measures Logistic Regression)

  thrice weekly for 12 weeks

Secondary Outcomes (1)

• Retention

  14 weeks

Study Arms (4)

1

PLACEBO COMPARATOR

microcrystalline cellulose

Drug: Disulfiram

2

EXPERIMENTAL

disulfiram at 250 mg/day

Drug: Disulfiram

3

EXPERIMENTAL

Disulfiram at 375 mg/day

Drug: Disulfiram

4

EXPERIMENTAL

Disulfiram at 500 mg/day

Drug: Disulfiram

Interventions

Disulfiram DRUG

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

1; 2; 3; 4

Eligibility Criteria

• Age: 18 Years - 65 Years
• Sex: all
• Healthy Volunteers: Yes
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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

You may not qualify if:

• 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.

Sponsors & Collaborators

• University of Arkansas: lead
• National Institute on Drug Abuse (NIDA): collaborator

Study Sites (1)

University of Arkansas for Medical Sciences

Little Rock, Arkansas, 72205, United States

Location

MeSH Terms

Conditions

Cocaine-Related Disorders

Interventions

Disulfiram

Condition Hierarchy (Ancestors)

Substance-Related Disorders; Chemically-Induced Disorders; Mental Disorders

Intervention Hierarchy (Ancestors)

Ditiocarb; Thiocarbamates; Carbamates; Acids, Acyclic; Carboxylic Acids; Organic Chemicals; Disulfides; Sulfides; Sulfur Compounds

Results Point of Contact

• Title: Dr. Alison Oliveto
• Organization: University of Arkansas for Medical Sciences

olivetoalison@uams.edu

501-526-8441

Study Officials

• Alison Oliveto, Ph.D.

  University of Arkansas

  PRINCIPAL INVESTIGATOR

Publication Agreements

• PI is Sponsor Employee: Yes

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: QUADRUPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR, OUTCOMES ASSESSOR
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: November 2, 2006
• First Posted: November 3, 2006
• Study Start: April 1, 2007
• Primary Completion: December 1, 2011
• Study Completion: December 1, 2011
• Last Updated: November 13, 2013
• Results First Posted: November 13, 2013

Record last verified: 2013-09

Locations

US (1)