Disulfiram for Cocaine Abuse

This study has been completed.
Sponsor:
Collaborator:
Information provided by (Responsible Party):
University of Arkansas
ClinicalTrials.gov Identifier:
NCT00395850
First received: November 2, 2006
Last updated: September 6, 2013
Last verified: September 2013
  Purpose

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.


Condition Intervention Phase
Cocaine Dependence
Drug: Disulfiram
Phase 2

Study Type: Interventional
Study Design: Allocation: Randomized
Endpoint Classification: Efficacy Study
Intervention Model: Parallel Assignment
Masking: Double Blind (Subject, Caregiver, Investigator, Outcomes Assessor)
Primary Purpose: Treatment
Official Title: Disulfiram for Cocaine Abuse

Resource links provided by NLM:


Further study details as provided by University of Arkansas:

Primary Outcome Measures:
  • Cocaine Use Over Time [ Time Frame: thrice weekly for 12 weeks ] [ Designated as safety issue: No ]
    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)


Secondary Outcome Measures:
  • Retention [ Time Frame: 14 weeks ] [ Designated as safety issue: No ]

Enrollment: 118
Study Start Date: April 2007
Study Completion Date: December 2011
Primary Completion Date: December 2011 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Placebo Comparator: 1
microcrystalline cellulose
Drug: Disulfiram
Disulfiram at 0, 250, 375, or 500 mg/day for 12 weeks
Experimental: 2
disulfiram at 250 mg/day
Drug: Disulfiram
Disulfiram at 0, 250, 375, or 500 mg/day for 12 weeks
Experimental: 3
Disulfiram at 375 mg/day
Drug: Disulfiram
Disulfiram at 0, 250, 375, or 500 mg/day for 12 weeks
Experimental: 4
Disulfiram at 500 mg/day
Drug: Disulfiram
Disulfiram at 0, 250, 375, or 500 mg/day for 12 weeks

  Eligibility

Ages Eligible for Study:   18 Years to 65 Years
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   Yes
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.
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT00395850

Locations
United States, Arkansas
University of Arkansas for Medical Sciences
Little Rock, Arkansas, United States, 72205
Sponsors and Collaborators
University of Arkansas
Investigators
Principal Investigator: Alison Oliveto, Ph.D. University of Arkansas
  More Information

No publications provided

Responsible Party: University of Arkansas
ClinicalTrials.gov Identifier: NCT00395850     History of Changes
Other Study ID Numbers: NIDA-13441, 5R01DA013441-02, 5R01DA013441-03, 5R01DA013441-04, 5R01DA013441-06, 1R01DA013441-01A1, 7R01DA013441-05, 5R01DA013441-09, 5R01DA013441-10, 5R01DA013441-08, R01DA013441, DPMC
Study First Received: November 2, 2006
Results First Received: March 14, 2013
Last Updated: September 6, 2013
Health Authority: United States: Food and Drug Administration

Keywords provided by University of Arkansas:
cocaine dependence
disulfiram
clinical trial
methadone maintenance
pharmacogenetics
dopamine beta-hydroxylase

Additional relevant MeSH terms:
Cocaine-Related Disorders
Substance-Related Disorders
Mental Disorders
Cocaine
Disulfiram
Vasoconstrictor Agents
Cardiovascular Agents
Therapeutic Uses
Pharmacologic Actions
Dopamine Uptake Inhibitors
Dopamine Agents
Neurotransmitter Agents
Molecular Mechanisms of Pharmacological Action
Neurotransmitter Uptake Inhibitors
Physiological Effects of Drugs
Anesthetics, Local
Anesthetics
Central Nervous System Depressants
Sensory System Agents
Peripheral Nervous System Agents
Central Nervous System Agents
Enzyme Inhibitors
Alcohol Deterrents

ClinicalTrials.gov processed this record on July 23, 2014