Pharmacogenetics of Disulfiram for Cocaine (Disulfiram)

February 4, 2017 updated by: Thomas R. Kosten, MD, Baylor College of Medicine

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.

Study Overview

Status

Completed

Conditions

Intervention / Treatment

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.

Study Type

Interventional

Enrollment (Actual)

93

Phase

  • Phase 2

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Locations

  • United States
    • Texas
      • Houston, Texas, United States, 77030
        • Michael E. DeBakey VA Medical Center

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

14 years to 60 years (Adult)

Accepts Healthy Volunteers

No

Genders Eligible for Study

All

Description

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

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: Treatment
  • Allocation: Randomized
  • Interventional Model: Parallel Assignment
  • Masking: Quadruple

Arms and Interventions

Participant Group / Arm
Intervention / Treatment
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 Names:
  • 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 Names:
  • Cognitive Behavioral Therapy
Other: Lactose
Lactose was added to both the active disulfiram and placebo doses so they tasted identical.
Other Names:
  • 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 Names:
  • Cognitive Behavioral Therapy
Other: Lactose
Lactose was added to both the active disulfiram and placebo doses so they tasted identical.
Other Names:
  • lactose suspension

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Time Frame
Urine Toxicology for Cocaine.
Time Frame: Thrice weekly, baseline through week 14.
Thrice weekly, baseline through week 14.

Secondary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Retention by Treatment Condition.
Time Frame: 12 weeks
Treatment retention for full 12 weeks of study.
12 weeks

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

Baylor College of Medicine

Collaborators

National Institute on Drug Abuse (NIDA)
Yale University

Publications and helpful links

The person responsible for entering information about the study voluntarily provides these publications. These may be about anything related to the study.

General Publications

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start

January 1, 2005

Primary Completion (Actual)

December 1, 2009

Study Completion (Actual)

December 1, 2009

Study Registration Dates

First Submitted

September 6, 2005

First Submitted That Met QC Criteria

September 6, 2005

First Posted (Estimate)

September 8, 2005

Study Record Updates

Last Update Posted (Actual)

March 15, 2017

Last Update Submitted That Met QC Criteria

February 4, 2017

Last Verified

February 1, 2017

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

  • NIDA-18197-2
  • P50DA018197-02 (U.S. NIH Grant/Contract)

Plan for Individual participant data (IPD)

Plan to Share Individual Participant Data (IPD)?

No

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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