Effects of Modafinil in Methamphetamine Dependence

Study Overview
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Brief Summary
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Methamphetamine dependence is a serious public health problem with no pharmacologic treatments currently available. Relapse rates are high in this population. Exposure to cues previously associated with methamphetamine use may induce profound craving in abstinent individuals. Chronic methamphetamine abuse is associated with selective cognitive deficits that may undermine successful participation in psychosocial treatments. Medications which improve cognitive deficits in methamphetamine-dependent individuals may improve abstinence rates, especially in the critical early period of recovery. Modafinil is an atypical stimulant medication with evidence to support its use in treating cocaine dependence and attention deficit/hyperactivity disorder. The proposed studies are designed to evaluate modafinil as a potential treatment for methamphetamine dependence and its cognitive sequelae.

Official Title
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Effects of Modafinil in Methamphetamine Dependence

Conditions
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Methamphetamine Dependence

Intervention / Treatment
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* Drug: Modafinil
* Drug: Placebo


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Subjects must be able to provide informed consent and function at an intellectual level sufficient to allow accurate completion of all assessment instruments. Subjects must meet DSM-IV criteria for methamphetamine dependence within the past six months. Subjects may meet criteria for abuse, but not dependence on any other substance with the exception of nicotine. Because of the high comorbidity of methamphetamine and nicotine dependence, excluding nicotine dependence would seriously compromise the feasibility of recruitment. Nicotine use immediately prior to the cue reactivity testing session will be controlled. Subjects must consent to remain abstinent from all drugs of abuse (except nicotine) for 24 hours prior to the cue reactivity testing sessions. Subjects must consent to random assignment to the modafinil vs. placebo conditions. Exclusion Criteria: Women who are pregnant, nursing or of childbearing potential and not practicing an effective means of birth control. Subjects with evidence of or a history of significant hematological, endocrine, cardiovascular, pulmonary, renal, gastrointestinal, or neurological disease as these conditions may affect heart rate or skin conductance measurement. Subjects with a history of or current psychotic disorder or bipolar affective disorder as these may impact cue reactivity. Subjects who are unwilling or unable to maintain abstinence from alcohol and other drugs of abuse (except nicotine) for 24 hours prior the cue procedures. Subjects meeting DSM-IV criteria for substance dependence (other than nicotine or methamphetamine as appropriate) within the past 60 days. Subjects currently taking B-blockers, anti-arrhythmic agents, psychostimulants or any other agents known to interfere with heart rate and skin conductance monitoring. Known or suspected hypersensitivity to modafinil. Individuals taking medications that could adversely interact with study medications. Subjects with a history of epilepsy or seizure disorder.

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 65 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Quadruple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: 1<br>Modafinil 400 mg daily | Drug: Modafinil<br>* 400 mg daily for four weeks<br>* Other names: Provigil;|
| Placebo Comparator: 2<br>Placebo | Drug: Placebo<br>* Placebo 2 tablets daily for 4 weeks<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Percentage of Participants With Methamphetamine-positive Urine Drug Screens | Percentage of participants with at least one biweekly urine drug screen positive for methamphetamine (4 weeks active treatment phase + medication-free safety visit at week 5) | 5 weeks | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Percent Change in California Verbal Learning Test From Baseline to Study Endpoint | Mean percent change in T scores (average total score of 6 trials) from baseline to study endpoint (Week 5) in study completers. Larger (more positive) percent change values indicate better outcomes. | Study baseline to study endpoint (Week 5) | 
| Percent Change in Symbol Digit Modalities Test From Baseline to Study Endpoint | Mean percent change in T scores from baseline to study endpoint (Week 5) in study completers. Larger (more positive) percent change values indicate better outcomes. | 5 Weeks | 
| Percent Change in Paced Auditory Serial Addition Test Scores From Baseline to Study Endpoint | Mean percent change of T scores from baseline to study endpoint (Week 5) in study completers. Min T score = 0, max T score = 100. Higher scores, greater (more positive) percent change indicate better outcomes. | 5 weeks | 
| Score on the Wisconsin Card Sort Test | Scores (T scores) on the Wisconsin Card Sort Test (total errors) at study endpoint (Week 5) in study completers, adjusted for age and education; min=0, max=100, higher numbers indicate better outcomes. | 5 weeks | 
| Percent Change in the Grooved Pegboard Test Score From Baseline to Study Endpoint | Percent change of T scores from baseline to study endpoint (Week 5) in study completers; T score min=0, max=100; higher scores (more positive change) indicate better outcome. | 5 weeks | 
| Percent Change in Shipley Institute of Living Scale Scores From Baseline to Study Endpoint | Percent change in scores (T scores) on the Shipley Abstract subscale from baseline to study endpoint (Week 5) in study completers; T scores min=0, max=100; larger positive values indicate better outcome. | 5 weeks | 
| Percentage Change in Beck Depression Inventory Scores | Percent change in BDI score from baseline to study endpoint in study completers; range =-100% to 100%, larger (more negative) change indicates better outcome. | 5 weeks | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Methamphetamine, Modafinil, Addiction, Craving, Cognitive