Pharmacogenetics of Disulfiram for Cocaine

Cocaine Dependence Clinical Trial

— Disulfiram  

Official title:

Effectiveness of Disulfiram for Treating Cocaine Dependence in Individuals With Different Dopamine Beta Hydroxylase (DBH) Genes

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT00149630
• Other study ID #: NIDA-18197-2
• Secondary ID: P50DA018197-02DP
• Status: Completed
• Phase: Phase 2
• First received: September 6, 2005
• Last updated: November 27, 2012
• Start date: January 2005
• Est. completion date: December 2009

Study information

• Verified date: November 2012
• Source: Baylor College of Medicine
• Contact: n/a
• Is FDA regulated: No
• Health authority: United States: Federal Government
• Study type: Interventional

Clinical Trial Summary

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.

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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 93
• Est. completion date: December 2009
• Est. primary completion date: December 2009
• Accepts healthy volunteers: No
• Gender: Both
• Age group: 18 Years to 64 Years

Eligibility

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 Design

Allocation: Randomized, Endpoint Classification: Efficacy Study, Intervention Model: Parallel Assignment, Masking: Double Blind (Subject, Caregiver, Investigator, Outcomes Assessor), Primary Purpose: Treatment

Related Conditions & MeSH terms

• Cocaine Dependence
• Cocaine-Related Disorders
• Opioid Dependence
• Opioid-Related Disorders

Intervention

Drug:
• Disulfiram
Disulfiram 250 mg/day by mouth daily during study weeks 2-13. Disulfiram discontinued during study weeks 14-15.
• Methadone
Initial dose 25 mg; increased by 5 mg at each subsequent daily dosing until 60 mg maintenace dose reached.

Behavioral:
• CBT
1-hour weekly, individual, manual-guided Cognitive Behaviorial Therapy.

Other:
• Lactose
Lactose was added to both the active disulfiram and placebo doses so they tasted identical.

Locations

Country	Name	City	State
United States	Michael E. DeBakey VA Medical Center	Houston	Texas

Sponsors (3)

Lead Sponsor	Collaborator
Baylor College of Medicine	National Institute on Drug Abuse (NIDA), Yale University

Country where clinical trial is conducted

United States, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Urine Toxicology for Cocaine.		Thrice weekly, baseline through week 14.	No
Secondary	Retention by Treatment Condition.	Treatment retention for full 12 weeks of study.	12 weeks	No