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Pharmacogenetics of Disulfiram for Cocaine

This study has been completed.
Sponsor:
Collaborators:
National Institute on Drug Abuse (NIDA)
Yale University
Information provided by (Responsible Party):
Thomas R. Kosten, MD, Baylor College of Medicine
ClinicalTrials.gov Identifier:
NCT00149630
First received: September 6, 2005
Last updated: November 27, 2012
Last verified: November 2012
History of Changes
  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 Dependence
 Drug: Disulfiram
Drug: Methadone
Behavioral: CBT
Other: Lactose
 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: Effectiveness of Disulfiram for Treating Cocaine Dependence in Individuals With Different Dopamine Beta Hydroxylase (DBH) Genes

Resource links provided by NLM:

U.S. FDA Resources

Further study details as provided by Baylor College of Medicine:

Primary Outcome Measures:
  • Urine Toxicology for Cocaine. [ Time Frame: Thrice weekly, baseline through week 14. ] [ Designated as safety issue: No ]

Secondary Outcome Measures:
  • Retention by Treatment Condition. [ Time Frame: 12 weeks ] [ Designated as safety issue: No ]
    Treatment retention for full 12 weeks of study.


Enrollment: 93
Study Start Date: January 2005
Study Completion Date: December 2009
Primary Completion Date: December 2009 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: Disulfiram, Methadone (w/lactose) & CBT Drug: Disulfiram
Disulfiram 250 mg/day by mouth daily during study weeks 2-13. Disulfiram discontinued during study weeks 14-15.
Other Name: Antabuse
Drug: Methadone
Initial dose 25 mg; increased by 5 mg at each subsequent daily dosing until 60 mg maintenace dose reached.
Other Names:
  • Symoron
  • Dolophine
  • Amidone
  • Methadose
  • Physeptone
  • Heptadon
Behavioral: CBT
1-hour weekly, individual, manual-guided Cognitive Behaviorial Therapy.
Other Name: Cognitive Behavioral Therapy
Other: Lactose
Lactose was added to both the active disulfiram and placebo doses so they tasted identical.
Other Name: lactose suspension
Active Comparator: Placebo, Methadone (w/lactose) & CBT Drug: Methadone
Initial dose 25 mg; increased by 5 mg at each subsequent daily dosing until 60 mg maintenace dose reached.
Other Names:
  • Symoron
  • Dolophine
  • Amidone
  • Methadose
  • Physeptone
  • Heptadon
Behavioral: CBT
1-hour weekly, individual, manual-guided Cognitive Behaviorial Therapy.
Other Name: Cognitive Behavioral Therapy
Other: Lactose
Lactose was added to both the active disulfiram and placebo doses so they tasted identical.
Other Name: lactose suspension

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 64 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);
  • 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

Locations
United States, Texas
Michael E. DeBakey VA Medical Center
Houston, Texas, United States, 77030
Sponsors and Collaborators
Baylor College of Medicine
National Institute on Drug Abuse (NIDA)
Yale University
Investigators
Principal Investigator: Thomas R. Kosten, MD Baylor College of Medicine
  More Information

No publications provided

Responsible Party: Thomas R. Kosten, MD, Professor, Baylor College of Medicine
ClinicalTrials.gov Identifier: NCT00149630     History of Changes
Other Study ID Numbers: NIDA-18197-2, P50DA018197-02, P50-DA18197-02, DPMC
Study First Received: September 6, 2005
Results First Received: October 22, 2012
Last Updated: November 27, 2012
Health Authority: United States: Federal Government

Keywords provided by Baylor College of Medicine:
Opioid Dependence
Substance Related Disorders

Additional relevant MeSH terms:
Opioid-Related Disorders
Cocaine-Related Disorders
Substance-Related Disorders
Mental Disorders
Disulfiram
Methadone
Enzyme Inhibitors
Molecular Mechanisms of Pharmacological Action
Pharmacologic Actions
Alcohol Deterrents
Central Nervous System Agents
 Therapeutic Uses
Analgesics, Opioid
Analgesics
Sensory System Agents
Peripheral Nervous System Agents
Physiological Effects of Drugs
Central Nervous System Depressants
Antitussive Agents
Respiratory System Agents
Narcotics

ClinicalTrials.gov processed this record on June 17, 2013