Disulfiram for Cocaine Abuse in Buprenorphine Treatment - Full Text View

Purpose

The investigators are proposing a placebo-controlled clinical trial to evaluate the efficacy and potential mechanisms of action of disulfiram (versus placebo) for treating cocaine abuse in subjects with concurrent opiate dependence and cocaine abuse or dependence maintained on buprenorphine/naloxone combination.

Condition	Intervention	Phase
Cocaine Dependence Opioid Dependency	Drug: Disulfiram Drug: Placebo	Phase 2

Study Type:	Interventional
Study Design:	Allocation: Randomized Endpoint Classification: Efficacy Study Intervention Model: Factorial Assignment Masking: Double Blind (Subject, Caregiver, Investigator, Outcomes Assessor) Primary Purpose: Treatment
Official Title:	Disulfiram for Cocaine Abuse in Buprenorphine Treatment

Resource links provided by NLM:

Drug Information available for: Dopamine Cocaine hydrochloride Disulfiram Buprenorphine Buprenorphine hydrochloride

U.S. FDA Resources

Further study details as provided by Yale University:

Primary Outcome Measures:

Cocaine abstinence [ Time Frame: 12 weeks ] [ Designated as safety issue: No ]

Secondary Outcome Measures:

Opioid abstinence [ Time Frame: 12 weeks ] [ Designated as safety issue: No ]

Enrollment:	177
Study Start Date:	October 2000
Study Completion Date:	February 2004
Primary Completion Date:	February 2004 (Final data collection date for primary outcome measure)

Arms	Assigned Interventions
Experimental: Disulfiram Disulfiram 250 mg per day	Drug: Disulfiram Disulfiram 250 mg per day
Placebo Comparator: Placebo Placebo	Drug: Placebo Placebo daily

Detailed Description:

The Specific Aims and hypotheses for the proposed study are as follows:

To compare the efficacy of disulfiram versus placebo for the treatment of buprenorphine maintained patients with concurrent opioid and cocaine dependence. Study hypothesis 1 is that disulfiram is superior to placebo.
To evaluate whether dopamine-B-hydroxylase (DBH) genotypes associated with high, intermediate or low enzyme activity predict responses to disulfiram treatment of cocaine use in buprenorphine treated subjects. Study hypothesis 2 is that disulfiram efficacy is higher in subjects with low DBH compared to subjects with high DBH.
To explore whether baseline measures of alcohol use predict response to disulfiram. Study Hypothesis 3 is that the effects of disulfiram on cocaine use are independent of the severity of baseline alcohol use.

Eligibility

Ages Eligible for Study:	18 Years to 45 Years
Genders Eligible for Study:	Both
Accepts Healthy Volunteers:	No

Criteria

Inclusion Criteria:

English speaking adults ages 18 - 45.
Meeting FDA criteria for agonist maintenance treatment and DSM-IV criteria for opioid dependence and cocaine dependence or abuse as assessed by SCID interview and documented by opioid positive and cocaine positive urine toxicology testing.
Women of childbearing age will be included provided they agree to adequate contraception and to monthly pregnancy testing during the course of the study.

Exclusion Criteria:

Current physiologic dependence on benzodiazepines or alcohol, unless first detoxified. Subjects who use/abuse alcohol will be included but will be cautioned about alcohol use during the study because of the possibility of an alcohol-disulfiram reaction.
Use of the antibiotic agents metronidazole or clotrimazole, which have disulfiram-like effects in combination with alcohol.
Presence of significant cardiovascular, renal, hepatic or neurologic illness. Subjects with markedly abnormal liver function tests (i.e., AST of ALT > 3X normal) will also be excluded.
Presence of any of the following cardiovascular risk factors:
- age > 45 years
- history of cocaine-related chest pain
- systolic blood pressure > 140 or diastolic blood pressure > 90
- evidence of ischemia or past myocardial infarction on EKG
- significant family history of risk (first degree relative with myocardial infarction prior to age 60)
- elevated cholesterol (> 300 mg/dl), elevated LDL (> 170 mg/dl) or low HDL (< 20 mg/dl)
Maintenance on methadone at doses greater than 30mg daily. Admittance to the study will only be offered to individuals who have been maintained on 30 mg of methadone or less daily for seven days prior to entering the study.
Current suicide or homicide risk or current psychotic disorder.
Inability to read or understand the symptom checklists.

Contacts and Locations

Please refer to this study by its ClinicalTrials.gov identifier: NCT00913484

Locations

United States, Connecticut
Yale University School of Medicine
New Haven, Connecticut, United States, 06519
The APT Foundation MRU
New Haven, Connecticut, United States, 06519

Sponsors and Collaborators

Yale University

National Institute on Drug Abuse (NIDA)

Investigators

Principal Investigator:

Richard S. Schottenfeld, M.D.

Yale University

More Information

No publications provided

Responsible Party:	Richard S. Schottenfeld, MD, Yale University School of Medicine
ClinicalTrials.gov Identifier:	NCT00913484 History of Changes
Other Study ID Numbers:	1R01DA12979, 1 R01 DA12979
Study First Received:	June 3, 2009
Last Updated:	June 3, 2009
Health Authority:	United States: Food and Drug Administration

Keywords provided by Yale University:

Disulfiram
Buprenorphine
Cocaine dependence
Opioid dependence
Dopamine-Beta-Hydroxylase

Additional relevant MeSH terms:

Cocaine-Related Disorders
Substance-Related Disorders
Mental Disorders
Buprenorphine
Cocaine
Disulfiram
Analgesics, Opioid
Analgesics
Sensory System Agents
Peripheral Nervous System Agents
Physiological Effects of Drugs
Pharmacologic Actions
Central Nervous System Agents
Therapeutic Uses

Central Nervous System Depressants
Narcotic Antagonists
Narcotics
Vasoconstrictor Agents
Cardiovascular Agents
Dopamine Uptake Inhibitors
Dopamine Agents
Neurotransmitter Agents
Molecular Mechanisms of Pharmacological Action
Neurotransmitter Uptake Inhibitors
Anesthetics, Local
Anesthetics
Enzyme Inhibitors
Alcohol Deterrents

ClinicalTrials.gov processed this record on May 16, 2013