Methamphetamine Dependence
Conditions
Keywords
Methamphetamine, Modafinil, Addiction, Craving, Cognitive
Brief summary
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.
Interventions
DRUGModafinil
400 mg daily for four weeks
DRUGPlacebo
Placebo 2 tablets daily for 4 weeks
Sponsors
Medical University of South Carolina
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
QUADRUPLE (Subject, Caregiver, Investigator, Outcomes Assessor)
Eligibility
Sex/Gender
ALL
Age
18 Years to 65 Years
Healthy volunteers
No
Inclusion criteria
1. Subjects must be able to provide informed consent and function at an intellectual level sufficient to allow accurate completion of all assessment instruments. 2. 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. 3. Subjects must consent to remain abstinent from all drugs of abuse (except nicotine) for 24 hours prior to the cue reactivity testing sessions. 4. Subjects must consent to random assignment to the modafinil vs. placebo conditions.
Exclusion criteria
1. Women who are pregnant, nursing or of childbearing potential and not practicing an effective means of birth control. 2. 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. 3. Subjects with a history of or current psychotic disorder or bipolar affective disorder as these may impact cue reactivity. 4. 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. 5. Subjects meeting DSM-IV criteria for substance dependence (other than nicotine or methamphetamine as appropriate) within the past 60 days. 6. Subjects currently taking B-blockers, anti-arrhythmic agents, psychostimulants or any other agents known to interfere with heart rate and skin conductance monitoring. 7. Known or suspected hypersensitivity to modafinil. 8. Individuals taking medications that could adversely interact with study medications. 9. Subjects with a history of epilepsy or seizure disorder.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Percentage of Participants With Methamphetamine-positive Urine Drug Screens | 5 weeks | 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) |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Percent Change in Symbol Digit Modalities Test From Baseline to Study Endpoint | 5 Weeks | 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. |
| Percent Change in Paced Auditory Serial Addition Test Scores From Baseline to Study Endpoint | 5 weeks | 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. |
| Score on the Wisconsin Card Sort Test | 5 weeks | 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. |
| Percent Change in California Verbal Learning Test From Baseline to Study Endpoint | Study baseline to study endpoint (Week 5) | 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. |
| Percent Change in Shipley Institute of Living Scale Scores From Baseline to Study Endpoint | 5 weeks | 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. |
| Percentage Change in Beck Depression Inventory Scores | 5 weeks | Percent change in BDI score from baseline to study endpoint in study completers; range =-100% to 100%, larger (more negative) change indicates better outcome. |
| Percent Change in the Grooved Pegboard Test Score From Baseline to Study Endpoint | 5 weeks | 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. |
Countries
United States
Participant flow
Pre-assignment details
The Enrollment number in the Protocol Section has been corrected (n=40) to appropriately match the number of participants listed in the Results Participant Flow section. The previous Protocol section incorrectly included a cohort (n=31) of healthy control subjects who underwent cognitive testing but did not participate in the modafinil trial.
Participants by arm
| Arm | Count |
|---|---|
| Modafinil Modafinil 400 mg daily
Modafinil: 400 mg daily for four weeks | 20 |
| Placebo Placebo
Placebo: Placebo 2 tablets daily for 4 weeks | 20 |
| Total | 40 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 |
|---|---|---|---|
| Overall Study | Lost to Follow-up | 11 | 7 |
Baseline characteristics
| Characteristic | Modafinil | Placebo | Total |
|---|---|---|---|
| Age, Continuous | 30.3 years STANDARD_DEVIATION 8.2 | 32.1 years STANDARD_DEVIATION 7.4 | 31.2 years STANDARD_DEVIATION 7.8 |
| Sex: Female, Male Female | 14 Participants | 13 Participants | 27 Participants |
| Sex: Female, Male Male | 6 Participants | 7 Participants | 13 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | 0 / 20 | 0 / 20 |
| other Total, other adverse events | 16 / 20 | 14 / 20 |
| serious Total, serious adverse events | 0 / 20 | 0 / 20 |
Outcome results
Primary
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)
Time frame: 5 weeks
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Modafinil | Percentage of Participants With Methamphetamine-positive Urine Drug Screens | 85 Percentage of participants |
| Placebo | Percentage of Participants With Methamphetamine-positive Urine Drug Screens | 65 Percentage of participants |
Secondary
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.
Time frame: 5 weeks
Population: Note: Total number of study completers = 22 (9 in Modafinil group and 13 in Placebo group). Beck Depression Inventory Scores at study endpoint were obtained in only 20 of 22 study completers (9 participants assigned to Modafinil and 11 participants assigned to Placebo).
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Modafinil | Percentage Change in Beck Depression Inventory Scores | -58.4 Percent change | Standard Deviation 52.7 |
| Placebo | Percentage Change in Beck Depression Inventory Scores | -43.5 Percent change | Standard Deviation 35.4 |
Secondary
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.
Time frame: Study baseline to study endpoint (Week 5)
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Modafinil | Percent Change in California Verbal Learning Test From Baseline to Study Endpoint | 20.6 Percent change, baseline-study endpoint | Standard Deviation 13.4 |
| Placebo | Percent Change in California Verbal Learning Test From Baseline to Study Endpoint | 14.8 Percent change, baseline-study endpoint | Standard Deviation 4.9 |
Secondary
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.
Time frame: 5 weeks
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Modafinil | Percent Change in Paced Auditory Serial Addition Test Scores From Baseline to Study Endpoint | 11.3 Percent change, baseline-study endpoint | Standard Deviation 23.5 |
| Placebo | Percent Change in Paced Auditory Serial Addition Test Scores From Baseline to Study Endpoint | 28.5 Percent change, baseline-study endpoint | Standard Deviation 61 |
Secondary
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.
Time frame: 5 weeks
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Modafinil | Percent Change in Shipley Institute of Living Scale Scores From Baseline to Study Endpoint | 4.1 T scores, percent change | Standard Deviation 7.1 |
| Placebo | Percent Change in Shipley Institute of Living Scale Scores From Baseline to Study Endpoint | 4.6 T scores, percent change | Standard Deviation 16.3 |
Secondary
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.
Time frame: 5 Weeks
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Modafinil | Percent Change in Symbol Digit Modalities Test From Baseline to Study Endpoint | 6.4 Percent change, baseline-study endpoint | Standard Deviation 15.2 |
| Placebo | Percent Change in Symbol Digit Modalities Test From Baseline to Study Endpoint | 10.0 Percent change, baseline-study endpoint | Standard Deviation 23.6 |
Secondary
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.
Time frame: 5 weeks
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Modafinil | Percent Change in the Grooved Pegboard Test Score From Baseline to Study Endpoint | 10.8 Percent change, baseline-study endpoint | Standard Deviation 40.7 |
| Placebo | Percent Change in the Grooved Pegboard Test Score From Baseline to Study Endpoint | 65.0 Percent change, baseline-study endpoint | Standard Deviation 149.9 |
Secondary
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.
Time frame: 5 weeks
Population: Note: Total number of study completers = 22 (9 in Modafinil group and 13 in Placebo group). The Wisconsin Card Sort Test was able to be completed in only 19 of 22 study completers (8 participants assigned to Modafinil and 11 participants assigned to Placebo).
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Modafinil | Score on the Wisconsin Card Sort Test | 44.6 T scores at study endpoint | Standard Deviation 14 |
| Placebo | Score on the Wisconsin Card Sort Test | 41.9 T scores at study endpoint | Standard Deviation 14.5 |