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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
  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
Intervention Model: Parallel Assignment
Masking: Quadruple (Participant, Care Provider, 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:


Further study details as provided by Thomas R. Kosten, MD, Baylor College of Medicine:

Primary Outcome Measures:
  • Urine Toxicology for Cocaine. [ Time Frame: Thrice weekly, baseline through week 14. ]

Secondary Outcome Measures:
  • Retention by Treatment Condition. [ Time Frame: 12 weeks ]
    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
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.
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
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.
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

Information from the National Library of Medicine

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Ages Eligible for Study:   18 Years to 64 Years   (Adult)
Sexes Eligible for Study:   All
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
Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): 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

Publications automatically indexed to this study by ClinicalTrials.gov Identifier (NCT Number):
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 ( U.S. NIH Grant/Contract )
First Submitted: September 6, 2005
First Posted: September 8, 2005
Results First Submitted: October 22, 2012
Results First Posted: December 28, 2012
Last Update Posted: March 15, 2017
Last Verified: February 2017
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: No

Keywords provided by Thomas R. Kosten, MD, Baylor College of Medicine:
Opioid Dependence
Substance Related Disorders

Additional relevant MeSH terms:
Cocaine-Related Disorders
Substance-Related Disorders
Chemically-Induced Disorders
Mental Disorders
Methadone
Cocaine
Disulfiram
Analgesics, Opioid
Narcotics
Central Nervous System Depressants
Physiological Effects of Drugs
Analgesics
Sensory System Agents
Peripheral Nervous System Agents
Antitussive Agents
Respiratory System Agents
Anesthetics, Local
Anesthetics
Vasoconstrictor Agents
Dopamine Uptake Inhibitors
Neurotransmitter Uptake Inhibitors
Membrane Transport Modulators
Molecular Mechanisms of Pharmacological Action
Dopamine Agents
Neurotransmitter Agents
Alcohol Deterrents
Acetaldehyde Dehydrogenase Inhibitors
Enzyme Inhibitors