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Pharmacogenetics of Disulfiram for Cocaine
This study is currently recruiting participants.
Verified by National Institute on Drug Abuse (NIDA), August 2008
Sponsors and Collaborators: National Institute on Drug Abuse (NIDA)
Yale University
University of Arkansas
University of Texas
Information provided by: National Institute on Drug Abuse (NIDA)
ClinicalTrials.gov Identifier: NCT00149630
  Purpose

Previous research has shown that disulfiram, a medication sometimes used for treating alcoholism, discourages cocaine use among cocaine addicts who are undergoing methadone treatment. By blocking the enzyme dopamine beta hydroxylase (DBH), disulfiram increases levels of dopamine and produces an unpleasant sense of hyperstimulation and discomfort in cocaine users. This study will evaluate the effectiveness of disulfiram in preventing drug relapse among cocaine and opiate addicts with varying inherited levels of DBH.


Condition Intervention Phase
Cocaine Dependence
Opioid Dependency
Drug: Disulfiram
Drug: Placebo
Phase II

Drug Information available for: Dopamine Dopamine hydrochloride Disulfiram 8-Azabicyclo(3.2.1)octane-2-carboxylic acid, 3-(benzoyloxy)-8-methyl-, methyl ester, (1R-(exo,exo))- Cocaine hydrochloride
U.S. FDA Resources
Study Type: Interventional
Study Design: Treatment, Randomized, Double Blind (Subject, Caregiver, Investigator, Outcomes Assessor), Placebo Control, Parallel Assignment, Efficacy Study
Official Title: Effectiveness of Disulfiram for Treating Cocaine Dependence in Individuals With Different Dopamine Beta Hydroxylase (DBH) Genes

Further study details as provided by National Institute on Drug Abuse (NIDA):

Primary Outcome Measures:
  • Self reports of cocaine and other drug use and cravings; measured throughout the study [ Time Frame: measured throughout the study ] [ Designated as safety issue: No ]

Estimated Enrollment: 200
Study Start Date: January 2005
Estimated Study Completion Date: June 2009
Estimated Primary Completion Date: June 2009 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
1: Experimental
Disulfiram
Drug: Disulfiram
250 mg/day
2: Placebo Comparator
Placebo
Drug: Placebo
Placebo daily dosing

Detailed Description:

Dopamine, a type of neurotransmitter, is the brain's "feel good" chemical. The amount of dopamine in the body may be an important factor in how cocaine addicts respond to treatment. Disulfiram, like cocaine, enhances dopamine activity. Upon taking disulfiram, subsequent intake of cocaine may elevate dopamine to excessive levels that produce extreme discomfort. DBH is an enzyme that breaks down dopamine. A particular variation in the DBH gene can affect the amount of dopamine that is released in the body. Therefore, cocaine addicts with varying DBH genes may respond differently to treatment. The purpose of this study is to compare the effectiveness of disulfiram in preventing relapse among methadone-maintained individuals addicted to both cocaine and opioids who may have different DBH genes.

This 17-week study will begin with a 2-week methadone stabilization period. Participants will then be randomly assigned to receive a daily dose of either 250 mg of disulfiram or placebo for 12 weeks, while concurrently receiving methadone treatment. All participants will stop receiving study medication at Week 14, at which point they will undergo a 4-week methadone detoxification period. Participants will report cocaine and other drug use, as well as any cocaine cravings that they experience. Cocaine levels will be monitored throughout the study with urine tests. The DBH gene of each participant will be examined to determine its specific make-up and any particular variations.

  Eligibility

Ages Eligible for Study:   18 Years to 65 Years
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  • Meets DSM-IV diagnosis criteria for opioid dependence, as determined by documentation of prior treatment for addiction; signs of withdrawal; self-reported history of dependence for at least 1 year; and a positive urine test for opioids
  • Meets DSM-IV diagnosis criteria for cocaine dependence, as determined by self-reported use of cocaine at least once weekly for at least 1 month prior to study entry; a positive urine test for cocaine; and a score greater than 3 on the Severity Dependence Scale
  • If female, willing to use contraception throughout the study

Exclusion criteria:

  • Meets DSM-IV diagnosis criteria for dependence on any drugs other than opiates, cocaine, or tobacco
  • Current major psychiatric illness, including schizophrenia, bipolar disorder, or other psychotic disorder
  • Current suicidal or homicidal ideation
  • Current use of a prescribed psychotropic medication that cannot be discontinued
  • History of or current major medical illness, including major heart, kidney, endocrine, or liver disorder; abnormal liver function (SGOT or SGPT levels three times greater than normal); or high blood pressure
  • High risk factor for heart disease, seizure disorders, or any illness for which disulfiram or methadone treatment would be inadvisable
  • Currently taking metronidazole or clotrimazole
  • Pregnant or breastfeeding
  Contacts and Locations
Please refer to this study by its ClinicalTrials.gov identifier: NCT00149630

Contacts
Contact: Tiffany L. Polk, MBA/HCM 832-689-1769 tiffanyp@bcm.edu
Contact: Grace Wu, MD 713-791-1414 ext 6384 ggwu@bcm.edu

Locations
United States, Texas
Michael E. DeBakey VA Medical Center Recruiting
Houston, Texas, United States, 77030
Contact: Thomas Kosten, MD     713-794-7032     kosten@bcm.edu    
Contact: Tiffany L. Polk, MBA/HCM     832-689-1769     tiffanyp@bcm.edu    
Sponsors and Collaborators
Yale University
University of Arkansas
University of Texas
Investigators
Principal Investigator: Thomas R. Kosten, MD Baylor College of Medicine
  More Information

Responsible Party: Baylor College of Medicine ( Thomas Kosten, MD )
Study ID Numbers: NIDA-18197-2, P50-18197-2, DPMC
Study First Received: September 6, 2005
Last Updated: August 12, 2008
ClinicalTrials.gov Identifier: NCT00149630  
Health Authority: United States: Federal Government

Keywords provided by National Institute on Drug Abuse (NIDA):
Opioid Dependency
Substance Related Disorders

Study placed in the following topic categories:
Disulfiram
Cocaine-Related Disorders
Dopamine
Mental Disorders
Substance-Related Disorders
Disorders of Environmental Origin
Cocaine
Ethanol

Additional relevant MeSH terms:
Molecular Mechanisms of Pharmacological Action
Therapeutic Uses
Enzyme Inhibitors
Central Nervous System Agents
Pharmacologic Actions
Alcohol Deterrents

ClinicalTrials.gov processed this record on January 16, 2009