Pharmacogenetics of Disulfiram for Cocaine

NCT ID: NCT00149630

Last Updated: 2017-03-15

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: PHASE2
• Total Enrollment: 93 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2005-01-31
• Study Completion Date: 2009-12-31

Brief 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.

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.

Conditions

Cocaine Dependence; Opioid Dependence

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: PARALLEL
• Primary Study Purpose: TREATMENT
• Blinding Strategy: QUADRUPLE

Study Groups

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.

Group Type: EXPERIMENTAL

Disulfiram

Intervention Type: DRUG

Disulfiram 250 mg/day by mouth daily during study weeks 2-13. Disulfiram discontinued during study weeks 14-15.

Methadone

Intervention Type: DRUG

Initial dose 25 mg; increased by 5 mg at each subsequent daily dosing until 60 mg maintenace dose reached.

CBT

Intervention Type: BEHAVIORAL

1-hour weekly, individual, manual-guided Cognitive Behaviorial Therapy.

Lactose

Intervention Type: OTHER

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

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.

Group Type: ACTIVE_COMPARATOR

Methadone

Intervention Type: DRUG

Initial dose 25 mg; increased by 5 mg at each subsequent daily dosing until 60 mg maintenace dose reached.

CBT

Intervention Type: BEHAVIORAL

1-hour weekly, individual, manual-guided Cognitive Behaviorial Therapy.

Lactose

Intervention Type: OTHER

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

Interventions

Disulfiram

Disulfiram 250 mg/day by mouth daily during study weeks 2-13. Disulfiram discontinued during study weeks 14-15.

Intervention Type: DRUG

Methadone

Initial dose 25 mg; increased by 5 mg at each subsequent daily dosing until 60 mg maintenace dose reached.

Intervention Type: DRUG

CBT

1-hour weekly, individual, manual-guided Cognitive Behaviorial Therapy.

Intervention Type: BEHAVIORAL

Lactose

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

Intervention Type: OTHER

Other Intervention Names

Antabuse; Symoron; Dolophine; Amidone; Methadose; Physeptone; Heptadon; Cognitive Behavioral Therapy; lactose suspension

Eligibility 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

• Minimum Eligible Age: 18 Years
• Maximum Eligible Age: 64 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

National Institute on Drug Abuse (NIDA)

NIH

Sponsor Role: collaborator

Yale University

OTHER

Sponsor Role: collaborator

Baylor College of Medicine

OTHER

Sponsor Role: lead

Responsible Party

Thomas R. Kosten, MD

Professor

Responsibility Role: PRINCIPAL_INVESTIGATOR

Principal Investigators

Thomas R. Kosten, MD

Role: PRINCIPAL_INVESTIGATOR

Baylor College of Medicine

Locations

Michael E. DeBakey VA Medical Center

Houston, Texas, United States

Countries

United States

References

Thomas PS Jr, Nielsen EM, Spellicy CJ, Harding MJ, Ye A, Patriquin M, Hamon SC, Kosten TR, Nielsen DA. The OPRD1 rs678849 variant influences outcome of disulfiram treatment for cocaine dependency in methadone-maintained patients. Psychiatr Genet. 2021 Jun 1;31(3):88-94. doi: 10.1097/YPG.0000000000000279.

Reference Type: DERIVED

PMID: 33953123 (View on PubMed)

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.

Reference Type: DERIVED

PMID: 23335901 (View on PubMed)

Other Identifiers

P50DA018197-02

Identifier Type: NIH

Identifier Source: secondary_id

View Link

NIDA-18197-2

Identifier Type: -

Identifier Source: org_study_id