Open-Label Disulfiram for Methamphetamine Dependence

• ClinicalTrials.gov Identifier: NCT00731133
• Recruitment Status: Completed
• First Posted: August 8, 2008
• Results First Posted: February 27, 2012
• Last Update Posted: February 27, 2012
• Sponsor: University of Arkansas
• Information provided by (Responsible Party): University of Arkansas

Study Description

Brief Summary:

This 8 week, open-label pilot clinical trial will examine the safety and tolerability of disulfiram at 250 mg/day in up to fifteen methamphetamine dependent individuals. After undergoing screening procedures (approximately one week), eligible subjects will enter the study proper attend clinic every weekday during week 1 of the trial in order to receive the disulfiram under observation and complete assessments. Then subjects will receive weekly blister packs of medication and attend clinic thrice weekly during weeks 2-6. During weeks 7-8, subjects no longer take disulfiram, are followed for two weeks, then referred to treatment elsewhere, if desired. Urine samples will be obtained and a disulfiram side-effects checklist will be completed thrice-weekly. Self-reported drug use, craving and mood ratings will be completed weekly. All subjects undergo cognitive behavioral therapy. Adjunctive contingency management procedures will be utilized to enhance retention. The primary outcomes of interest include retention, side-effects, and drug use. Our hypothesis is that disulfiram will be well tolerated in this population.

Condition or disease	Intervention/treatment	Phase
Methamphetamine Dependence	Drug: Disulfiram	Phase 1; Phase 2

Detailed Description:

This 8 week, open-label pilot clinical trial will examine the safety and tolerability of disulfiram at 250 mg/day in up to fifteen methamphetamine dependent individuals. After undergoing screening procedures (approximately one week), eligible subjects will enter the study proper attend clinic every weekday during week 1 of the trial in order to receive the disulfiram under observation and complete assessments. Then subjects will receive weekly blister packs of medication and attend clinic thrice weekly during weeks 2-6. During weeks 7-8, subjects no longer take disulfiram, are followed for two weeks, then referred to treatment elsewhere, if desired. Urine samples will be obtained and a disulfiram side-effects checklist will be completed thrice-weekly. Self-reported drug use, craving and mood ratings will be completed weekly. All subjects undergo cognitive behavioral therapy. Adjunctive contingency management procedures will be utilized to enhance retention. The primary outcomes of interest include retention, side-effects, and drug use. Results of this study will provide initial safety and drug use data for grant applications proposing to examine the clinical efficacy of disulfiram or similar agents to for treating methamphetamine dependence under placebo-controlled, double-blind conditions.

Study Design

• Study Type: Interventional (Clinical Trial)
• Actual Enrollment: 15 participants
• Allocation: N/A
• Intervention Model: Single Group Assignment
• Masking: None (Open Label)
• Primary Purpose: Treatment
• Official Title: Open-Label Pilot Study of Disulfiram for Methamphetamine Dependence
• Study Start Date: August 2008
• Actual Primary Completion Date: September 2010
• Actual Study Completion Date: September 2010

Arms and Interventions

Arm	Intervention/treatment
Disulfiram; Disulfiram at 250 mg daily	Drug: Disulfiram; 250 mg/day; Other Name: Antabuse

Outcome Measures

Primary Outcome Measures :

1. Side Effects Checklist [ Time Frame: Weekly for six weeks ]
   It consists of 25 items describing side effects specific to disulfiram alone or combined with alcohol or cocaine that are rated on a scale from 0 (not at all) to 4 (very much). Total scores range from 0 (minimum) to 100 (maximum). Data were entered into a mixed model ANOVA in order to determine whether scores significantly changed over time. A slope and standard deviation describing this change over time were generated and used as our outcome measures.

Secondary Outcome Measures :

1. Proportion of Amphetamine-positive Urine Samples [ Time Frame: thrice weekly for 6 weeks ]
   the proportion of urine samples positive for amphetamine. Data were entered into a mixed model ANOVA in order to determine whether scores significantly changed over time. A slope and standard deviation describing this change over time were generated and used as our outcome measures.

Eligibility Criteria

• Ages Eligible for Study: 18 Years to 65 Years (Adult, Older Adult)
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: No

Criteria

Inclusion Criteria:

• 18-65 years old
• not currently enrolled in a treatment program
• subjects must have a history of methamphetamine use with recent use confirmed by a positive urine toxicology screen for amphetamines during the month prior to study entry
• subjects must meet DSM-IV criteria for amphetamine dependence as assessed by the substance abuse section of the Structured Clinical Interview for DSM-IV (SCID)
• women of childbearing age must have a negative pregnancy test to enroll in this study, agree to monthly pregnancy testing, and agree to use appropriate forms of birth control for the duration of the study.

Exclusion Criteria:

• current diagnosis of alcohol physical dependence
• significant medical conditions such as abnormal liver function (e.g., laboratory findings on ALT or AST greater than three times normal), active hepatitis, uncontrolled hypertension, a current cardiac condition or high risk of cardiovascular disease (see section c.1), seizure disorders, or another significant underlying medical condition which would contraindicate disulfiram treatment
• meeting DSM-IV psychiatric classifications for schizophrenia, bipolar disorder, or other psychotic disorders
• exhibiting current suicidality or homicidality
• pregnancy or breastfeeding
• current use of a prescribed psychotropic medication (e.g., antidepressants, anxiolytics, antipsychotics, anticonvulsants, etc.) which cannot be discontinued
• current use of medications such as anticoagulants, isoniazid, metronidazole, clotrimazole, and paraldehyde

Contacts and Locations

Locations

United States, Arkansas

University of Arkansas for Medical Sciences

Little Rock, Arkansas, United States, 72205

Sponsors and Collaborators

University of Arkansas

Investigators

• Principal Investigator: Alison Oliveto, PhD; University of Arkansas

More Information

• Responsible Party: University of Arkansas
• ClinicalTrials.gov Identifier: NCT00731133
• Other Study ID Numbers: 5-P50-DA018197-105242; 5P50DA018197 ( U.S. NIH Grant/Contract ); DPMCDA
• First Posted: August 8, 2008
• Results First Posted: February 27, 2012
• Last Update Posted: February 27, 2012
• Last Verified: January 2012

Keywords provided by University of Arkansas:

disulfiram; methamphetamine dependence; open label

Additional relevant MeSH terms:

Disulfiram; Alcohol Deterrents; Acetaldehyde Dehydrogenase Inhibitors; Enzyme Inhibitors; Molecular Mechanisms of Pharmacological Action