Pharmacogenetics of Disulfiram for Cocaine

Study Overview
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Brief Summary
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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
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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.

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

Conditions
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Cocaine Dependence, Opioid Dependence

Intervention / Treatment
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* Drug: Disulfiram
* Drug: Methadone
* Behavioral: CBT
* Other: Lactose


Participation Criteria
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Eligibility Criteria
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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

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 64 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Quadruple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Disulfiram, Methadone (w/lactose) & CBT<br>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<br>* Disulfiram 250 mg/day by mouth daily during study weeks 2-13. Disulfiram discontinued during study weeks 14-15.<br>* Other names: Antabuse;Drug: Methadone<br>* Initial dose 25 mg; increased by 5 mg at each subsequent daily dosing until 60 mg maintenace dose reached.<br>* Other names: Heptadon;Behavioral: CBT<br>* 1-hour weekly, individual, manual-guided Cognitive Behaviorial Therapy.<br>* Other names: Cognitive Behavioral Therapy;Other: Lactose<br>* Lactose was added to both the active disulfiram and placebo doses so they tasted identical.<br>* Other names: lactose suspension;|
| Active Comparator: Placebo, Methadone (w/lactose) & CBT<br>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<br>* Initial dose 25 mg; increased by 5 mg at each subsequent daily dosing until 60 mg maintenace dose reached.<br>* Other names: Heptadon;Behavioral: CBT<br>* 1-hour weekly, individual, manual-guided Cognitive Behaviorial Therapy.<br>* Other names: Cognitive Behavioral Therapy;Other: Lactose<br>* Lactose was added to both the active disulfiram and placebo doses so they tasted identical.<br>* Other names: lactose suspension;|

What is the study measuring?
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Primary Outcome Measures

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

Secondary Outcome Measures

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

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Opioid Dependence, Substance Related Disorders