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Pharmacogenetics of Disulfiram for Cocaine (Disulfiram)

This study has been completed.
Sponsor:
ClinicalTrials.gov Identifier:
NCT00149630
First Posted: September 8, 2005
Last Update Posted: March 15, 2017
The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details.
Collaborators:
National Institute on Drug Abuse (NIDA)
Yale University
Information provided by (Responsible Party):
Thomas R. Kosten, MD, Baylor College of Medicine
September 6, 2005
September 8, 2005
October 22, 2012
December 28, 2012
March 15, 2017
January 2005
December 2009   (Final data collection date for primary outcome measure)
Urine Toxicology for Cocaine. [ Time Frame: Thrice weekly, baseline through week 14. ]
Urine toxicology for cocaine
Complete list of historical versions of study NCT00149630 on ClinicalTrials.gov Archive Site
Retention by Treatment Condition. [ Time Frame: 12 weeks ]
Treatment retention for full 12 weeks of study.
Self reports of cocaine and other drug use and craving
Not Provided
Not Provided
 
Pharmacogenetics of Disulfiram for Cocaine
Effectiveness of Disulfiram for Treating Cocaine Dependence in Individuals With Different Dopamine Beta Hydroxylase (DBH) Genes
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.

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.

Interventional
Phase 2
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
Primary Purpose: Treatment
  • Cocaine Dependence
  • Opioid Dependence
  • 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
  • Experimental: Disulfiram, Methadone (w/lactose) & CBT
    Participants are randomly assigned to receive a daily dose of 250 mg of disulfiram 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.
    Interventions:
    • Drug: Disulfiram
    • Drug: Methadone
    • Behavioral: CBT
    • Other: Lactose
  • Active Comparator: Placebo, Methadone (w/lactose) & CBT
    Participants are randomly assigned to receive a daily dose of a sugar pill to mimic the experimental drug disulfiram for 12 weeks, while concurrently receiving methadone treatment. All participants will stop receiving all medication at week 14, at which point they will undergo a 4-week methadone detoxification period.
    Interventions:
    • Drug: Methadone
    • Behavioral: CBT
    • Other: Lactose
Spellicy CJ, Kosten TR, Hamon SC, Harding MJ, Nielsen DA. The MTHFR C677T Variant is Associated with Responsiveness to Disulfiram Treatment for Cocaine Dependency. Front Psychiatry. 2013 Jan 14;3:109. doi: 10.3389/fpsyt.2012.00109. eCollection 2012.

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Completed
93
December 2009
December 2009   (Final data collection date for primary outcome measure)

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
Sexes Eligible for Study: All
18 Years to 64 Years   (Adult)
No
Contact information is only displayed when the study is recruiting subjects
United States
 
 
NCT00149630
NIDA-18197-2
P50DA018197-02 ( U.S. NIH Grant/Contract )
Yes
Not Provided
Plan to Share IPD: No
Thomas R. Kosten, MD, Baylor College of Medicine
Baylor College of Medicine
  • National Institute on Drug Abuse (NIDA)
  • Yale University
Principal Investigator: Thomas R. Kosten, MD Baylor College of Medicine
Baylor College of Medicine
February 2017

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP