Cocaine Dependence, Opioid Dependence
Conditions
Keywords
Opioid Dependence, Substance Related Disorders
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.
Interventions
DRUGDisulfiram
Disulfiram 250 mg/day by mouth daily during study weeks 2-13. Disulfiram discontinued during study weeks 14-15.
DRUGMethadone
Initial dose 25 mg; increased by 5 mg at each subsequent daily dosing until 60 mg maintenace dose reached.
BEHAVIORALCBT
1-hour weekly, individual, manual-guided Cognitive Behaviorial Therapy.
OTHERLactose
Lactose was added to both the active disulfiram and placebo doses so they tasted identical.
Sponsors
National Institute on Drug Abuse (NIDA)
Yale University
Baylor College of Medicine
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
QUADRUPLE (Subject, Caregiver, Investigator, Outcomes Assessor)
Eligibility
Sex/Gender
ALL
Age
18 Years to 64 Years
Healthy volunteers
No
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
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Urine Toxicology for Cocaine. | Thrice weekly, baseline through week 14. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Retention by Treatment Condition. | 12 weeks | Treatment retention for full 12 weeks of study. |
Countries
United States
Participant flow
Recruitment details
The 74 opioid and cocaine dependent subjects were drawn from a sample of 93 candidates who entered into a 2-week screening period for stabilization on methadone maintenance between 2005 and 2006 at Yale University (n=40) and then from between 2006 and 2008 at Baylor College of Medicine (n=53).
Pre-assignment details
Eleven subjects were excluded prior to randomization because they did not have at least one urine toxicology positive for opiates or cocaine metabolites during the two-week screening. Another eight subjects were lost to follow-up prior to randomization.
Participants by arm
| Arm | Count |
|---|---|
| Disulfiram 250 mg/day with methadone daily during study weeks 2-13. Medication will be discontinued during study weeks 14-15. | 34 |
| Placebo Inactive medication (placebo) with methadone daily during study weeks 2-13. Inactive medication will be discontinued during study weeks 14-15. | 40 |
| Total | 74 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 |
|---|---|---|---|
| Overall Study | Adverse Event | 2 | 0 |
| Overall Study | Incarceration | 2 | 0 |
| Overall Study | Treatment Programs | 4 | 5 |
Baseline characteristics
| Characteristic | Placebo | Disulfiram | Total |
|---|---|---|---|
| Age, Categorical <=18 years | 0 Participants | 0 Participants | 0 Participants |
| Age, Categorical >=65 years | 0 Participants | 0 Participants | 0 Participants |
| Age, Categorical Between 18 and 65 years | 40 Participants | 34 Participants | 74 Participants |
| Age, Continuous | 40 years STANDARD_DEVIATION 10 | 37.5 years STANDARD_DEVIATION 10.5 | 38.75 years STANDARD_DEVIATION 10 |
| Region of Enrollment United States | 40 participants | 34 participants | 74 participants |
| Sex: Female, Male Female | 12 Participants | 10 Participants | 22 Participants |
| Sex: Female, Male Male | 28 Participants | 24 Participants | 52 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | — / — | — / — |
| other Total, other adverse events | 3 / 34 | 1 / 40 |
| serious Total, serious adverse events | 0 / 34 | 0 / 40 |
Outcome results
Primary
Urine Toxicology for Cocaine.
Time frame: Thrice weekly, baseline through week 14.
Population: 74 cocaine and opioid-codependent (DSM-V) subjects were stabilized on methadone for 2 weeks and subsequently randomized into disulfiram (250mg/day, n=34) and placebo groups (n=40) for 10 weeks. We genotyped the DBH gene polymorphism that reduces DBH enzyme levels and evaluated its role for increasing cocaine free urines with disulfiram.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Placebo CC | Urine Toxicology for Cocaine. | 84 % cocaine + urines over 2 week blocks | Standard Error 5 |
| Placebo CT/TT | Urine Toxicology for Cocaine. | 68 % cocaine + urines over 2 week blocks | Standard Error 5 |
| Disulfiram CC | Urine Toxicology for Cocaine. | 56 % cocaine + urines over 2 week blocks | Standard Error 5 |
| Disulfiram CT/TT | Urine Toxicology for Cocaine. | 67 % cocaine + urines over 2 week blocks | Standard Error 5 |
Secondary
Retention by Treatment Condition.
Treatment retention for full 12 weeks of study.
Time frame: 12 weeks
Population: 74 cocaine and opioid-codependent(DSM-V)subjects were stabilized on methadone for 2 weeks and subsequently randomized into disulfiram (250 mg/day, n=34) and placebo groups (n=40) for 10 weeks. We genotyped the DBH gene polymorphism that reduced DBH enzyme levels and evaluated its role for increasing cocaine free urines with disulfiram.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Placebo CC | Retention by Treatment Condition. | 77 % of subjects who complete 12 wks study |
| Placebo CT/TT | Retention by Treatment Condition. | 87 % of subjects who complete 12 wks study |