Methamphetamine Dependence
Conditions
Keywords
disulfiram, methamphetamine dependence, open label
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.
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.
Interventions
DRUGDisulfiram
250 mg/day
Sponsors
University of Arkansas
Study design
Allocation
NA
Intervention model
SINGLE_GROUP
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to 65 Years
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
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| 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
| Measure | Time frame | Description |
|---|---|---|
| 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. |
Countries
United States
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| Disulfiram Disulfiram at 250 mg daily | 15 |
| Total | 15 |
Withdrawals & dropouts
| Period | Reason | FG000 |
|---|---|---|
| Overall Study | Withdrawal by Subject | 10 |
Baseline characteristics
| Characteristic | Disulfiram |
|---|---|
| Age, Categorical <=18 years | 0 Participants |
| Age, Categorical >=65 years | 0 Participants |
| Age, Categorical Between 18 and 65 years | 15 Participants |
| Age Continuous | 35.93 years STANDARD_DEVIATION 9.29 |
| Region of Enrollment United States | 15 participants |
| Sex: Female, Male Female | 5 Participants |
| Sex: Female, Male Male | 10 Participants |
Adverse events
| Event type | EG000 affected / at risk |
|---|---|
| deaths Total, all-cause mortality | — / — |
| other Total, other adverse events | 7 / 15 |
| serious Total, serious adverse events | 0 / 15 |
Outcome results
Primary
Side Effects Checklist
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
Population: 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 | Measure | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|
| Disulfiram 250 mg | Side Effects Checklist | 9.6515 units on a scale | Standard Deviation 2.475 |
Comparison: Open-label study testing for change in side-effects ratings over time (i.e., slope).p-value: 0.0595% CI: [0.7858, 4.5073]Mixed Models Analysis
Secondary
Proportion of Amphetamine-positive Urine Samples
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
Population: 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 | Measure | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|
| Disulfiram 250 mg | Proportion of Amphetamine-positive Urine Samples | 0.3639 proportion of urines positive for amphet | Standard Deviation 0.1113 |
Comparison: Open label study testing changes in amphetamine use over time (i.e., slope).p-value: 0.0595% CI: [-0.8075, 0.0615]Mixed Models Analysis