Open-Label Disulfiram for Methamphetamine Dependence

• Sponsor: University of Arkansas (Other)
• Overall Status: Completed
• CT.gov ID: NCT00731133
• Collaborator: (none)
• Enrollment: 15
• Location: 1
• Arm: 1
• Duration (Months): 25
• Patients Per Site Per Month: 0.6

Study Details

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
• 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: Aug 1, 2008
• Actual Primary Completion Date: Sep 1, 2010
• Actual Study Completion Date: Sep 1, 2010

Arms and Interventions

Arm	Intervention/Treatment
Other: Disulfiram Disulfiram at 250 mg daily	Drug: Disulfiram; 250 mg/day; Other Names: Antabuse

Outcome Measures

Primary Outcome Measures

1. Side Effects Checklist [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 [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

Criteria

• Ages Eligible for Study: 18 Years to 65 Years
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: No

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

	Site	City	State	Country	Postal Code
1	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

Study Documents (Full-Text)

None provided.

More Information

Publications

None provided.

• Responsible Party: University of Arkansas
• ClinicalTrials.gov Identifier: NCT00731133
• Other Study ID Numbers: 5-P50-DA018197-105242; 5P50DA018197; DPMCDA
• First Posted: Aug 8, 2008
• Last Update Posted: Feb 27, 2012
• Last Verified: Jan 1, 2012

• Keywords provided by University of Arkansas: disulfiram; methamphetamine dependence; open label
• Additional relevant MeSH terms: Disulfiram

Study Results

Participant Flow

Arm/Group Title	Disulfiram
Arm/Group Description	Disulfiram at 250 mg daily
Period Title: Overall Study
STARTED	15
COMPLETED	5
NOT COMPLETED	10

Baseline Characteristics

Arm/Group Title	Disulfiram
Arm/Group Description	Disulfiram at 250 mg daily
Overall Participants	15
Age (Count of Participants)
<=18 years	0 0%
Between 18 and 65 years	15 100%
>=65 years	0 0%
Age (years) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [years]	35.93 (9.29)
Sex: Female, Male (Count of Participants)
Female	5 33.3%
Male	10 66.7%
Region of Enrollment (participants) [Number]
United States	15 100%

Outcome Measures

1. Primary Outcome

Title	Side Effects Checklist
Description	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.
Time Frame	Weekly for six weeks

Outcome Measure Data

Analysis Population Description

Those who received more than one dose of disulfiram and/or completed more than one set of assessments during the protocol. Of the 15 participants who entered the study, one participant only attended clinic one day and so data were analyzed for 14 participants.

Arm/Group Title	Disulfiram 250 mg
Arm/Group Description
Measure Participants	14
Least Squares Mean (Standard Deviation) [units on a scale]	9.6515 (2.4750)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Disulfiram 250 mg
	Comments	Open-label study testing for change in side-effects ratings over time (i.e., slope).
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	0.05
	Comments
	Method	Mixed Models Analysis
	Comments	7,24
Method of Estimation	Estimation Parameter	Slope
	Estimated Value	2.6466
	Confidence Interval	(2-Sided) 95%; .7858 to 4.5073
	Parameter Dispersion	Type: Standard Error of the Mean; Value: 0.9016
	Estimation Comments

2. Secondary Outcome

Title	Proportion of Amphetamine-positive Urine Samples
Description	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.
Time Frame	thrice weekly for 6 weeks

Outcome Measure Data

Analysis Population Description

Only data from participants who received more than one dose of disulfiram were analyzed. Of the 15 participants who entered the study, one participant received only one dose so data from 14 participants were analyzed.

Arm/Group Title	Disulfiram 250 mg
Arm/Group Description
Measure Participants	14
Least Squares Mean (Standard Deviation) [proportion of urines positive for amphet]	0.3639 (0.1113)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Disulfiram 250 mg
	Comments	Open label study testing changes in amphetamine use over time (i.e., slope).
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	0.05
	Comments
	Method	Mixed Models Analysis
	Comments	7,24
Method of Estimation	Estimation Parameter	Slope
	Estimated Value	-0.3730
	Confidence Interval	(2-Sided) 95%; -0.8075 to 0.06150
	Parameter Dispersion	Type: Standard Error of the Mean; Value: 0.2196
	Estimation Comments

Adverse Events

Time Frame	6 weeks
Arm/Group Title	Disulfiram
Arm/Group Description	Disulfiram at 250 mg daily
All Cause Mortality
	Disulfiram
	Affected / at Risk (%)	# Events
Total	/ (NaN)
Serious Adverse Events
	Disulfiram
	Affected / at Risk (%)	# Events
Total	0/15 (0%)
Other (Not Including Serious) Adverse Events
	Disulfiram
	Affected / at Risk (%)	# Events
Total	7/15 (46.7%)
Cardiac disorders
Increased blood pressure	1/14 (7.1%)	1
Gastrointestinal disorders
Nausea/Vomitting	4/14 (28.6%)	5
Stomach Bloating	1/14 (7.1%)	1
Metallic Taste	1/14 (7.1%)	1
General disorders
Sleepiness	1/14 (7.1%)	1
Dizziness	1/14 (7.1%)	1
Nervous system disorders
Headache	2/14 (14.3%)	2
Blurry vision	1/14 (7.1%)	1
Psychiatric disorders
Confusion	1/14 (7.1%)	1
Anxiety/Racing Heart	1/14 (7.1%)	1

Limitations/Caveats

Large dropout so few participants had data throughout the trial. No control group so cannot determine whether side effects were related to disulfiram or an artifact of participation.

More Information

Certain Agreements

All Principal Investigators ARE employed by the organization sponsoring the study.

There is NOT an agreement between Principal Investigators and the Sponsor (or its agents) that restricts the PI's rights to discuss or publish trial results after the trial is completed.