Cocaine-Related Disorders
Conditions
Brief summary
Cocaine dependence is a major public health problem; an effective primary treatment for cocaine dependent individuals has yet to be found. The purpose of this study is to examine the effects of d-amphetamine and modafinil, when given alone and in combination, in treating cocaine dependent individuals.
Detailed description
Cocaine is a strong central nervous system stimulant that is widely abused throughout the United Sates. Due to its widespread use, it is important to develop an effective treatment for cocaine dependence. Modafinil is a glutamate-enhancing agent. D-amphetamine is a central nervous system stimulant that is approved to treat individuals with narcolepsy and attention deficit disorder. Both modafinil and d-amphetamine may be effective treatments for cocaine dependence. The purpose of this study is to examine the effectiveness of modafinil and d-amphetamine, alone and in combination, in treating cocaine dependent individuals. This study will last 16 weeks. Participants will be randomly assigned to one of four groups: 1) 60 mg dose of d-amphetamine; 2) 400 mg dose of modafinil; 3) 30 mg dose of d-amphetamine combined with 200 mg dose of modafinil; and 4) placebo. All participants will receive 200 mg of modafinil over 4 days.
Interventions
DRUGD-Amphetamine 30mg
DRUGD-Amphetamine 60mg
DRUGModafinil 200mg
DRUGModafinil 400mg
BEHAVIORALTherapy
Manual-based, cognitive-behavioral therapy was provided for 1 hour each week by master's-level therapists. The cognitive-behavioral therapy emphasized relapse prevention and coping skills.
DRUGPlacebo
Sponsors
National Institute on Drug Abuse (NIDA)
The University of Texas Health Science Center, Houston
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 55 Years
Healthy volunteers
Yes
Inclusion criteria
* Meets Structured Clinical Interview for Diagnostic and Statistical Manual of Mental Disorders-IV (SCID) criteria for cocaine abuse or dependence * In general good health. Individuals who are HIV-positive will not be excluded if in good general health, unless medication interactions exist.
Exclusion criteria
* Meets diagnostic criteria for psychiatric disorders, including other forms of drug dependence, other than nicotine * Current cardiovascular disease, as determined by an electrocardiogram * On probation or parole if the circumstances do not allow study completion or if ethical constraints of supervision do not allow confidentiality * Previously received treatment with d-amphetamine, modafinil, or aripiprazole * Currently receiving prescribed medication
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Cocaine Use as Assessed by the Treatment Effectiveness Score (TES), Which is the Total Number of Cocaine-negative Urines During Treatment | 16 weeks |
| Retention as Indicated by the Number of Participants Who Completed 16 Weeks of Treatment | 16 weeks |
| Retention as Indicated by the Number of Participants Who Remained in the Study | 16 weeks |
Secondary
| Measure | Time frame |
|---|---|
| Medication Compliance as Indicated by Percentage of Pills Taken According to Self-report | 16 weeks |
| Medication Compliance as Indicated by Percentage of Riboflavin-positive Urine Samples | 16 weeks |
Countries
United States
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| D-Amphetamine 60mg + Therapy During the 16 weeks of outpatient treatment, participants took three capsules daily (two in the morning, one in the afternoon). All active and placebo capsules were identical in appearance and each contained 50mg riboflavin for subsequent evaluation of medication compliance. Medication administration was initiated during a 5 day run-up period. d-Amphetamine SR (Dexedrine Spansules) started at 15 mg (day 1-2), increased to 30mg (day3; 15mg, BID), 45mg (day4; 15mg, TID), and 60mg (day5; 15mg bid plus 30mg qd). A 5-day dose reduction schedule occurred at week 17.
Manual-based, cognitive-behavioral therapy was provided for 1 hour each week by master's-level therapists. The cognitive-behavioral therapy emphasized relapse prevention and coping skills. | 22 |
| Modafinil 400mg + Therapy During the 16 weeks of outpatient treatment, participants took three capsules daily (two in the morning, one in the afternoon). All active and placebo capsules were identical in appearance and each contained 50mg riboflavin for subsequent evaluation of medication compliance. Medication administration was initiated during a 5 day run-up period. Modafinil started at 200mg (day1) and increased to 400mg (days2-5). A 5-day dose reduction schedule occurred at week 17.
Manual-based,cognitive-behavioral therapy was provided for 1 hour each week by master's-level therapists. The cognitive-behavioral therapy emphasized relapse prevention and coping skills. | 20 |
| Modafinil 200mg + D-Amphetamine 30mg + Therapy During the 16 weeks of outpatient treatment, participants took three capsules daily (two in the morning, one in the afternoon). All active and placebo capsules were identical in appearance and each contained 50mg riboflavin for subsequent evaluation of medication compliance. Medication administration was initiated during a 5 day run-up period. For the combination condition, dosages of modafinil and d-amphetamine were escalated to one-half of that for the single medication conditions. A 5-day dose reduction schedule occurred at week 17.
Manual-based,cognitive-behavioral therapy was provided for 1 hour each week by master's-level therapists. The cognitive-behavioral therapy emphasized relapse prevention and coping skills. | 15 |
| Placebo + Therapy During the 16 weeks of outpatient treatment, participants took three capsules daily (two in the morning, one in the afternoon). All active and placebo capsules were identical in appearance and each contained 50mg riboflavin for subsequent evaluation of medication compliance.
Manual-based,cognitive-behavioral therapy was provided for 1 hour each week by master's-level therapists. The cognitive-behavioral therapy emphasized relapse prevention and coping skills. | 16 |
| Total | 73 |
Baseline characteristics
| Characteristic | D-Amphetamine 60mg + Therapy | Modafinil 400mg + Therapy | Modafinil 200mg + D-Amphetamine 30mg + Therapy | Placebo + Therapy | Total |
|---|---|---|---|---|---|
| Age, Continuous | 44.3 years STANDARD_DEVIATION 6.5 | 42.6 years STANDARD_DEVIATION 8.3 | 41.2 years STANDARD_DEVIATION 8.5 | 41.9 years STANDARD_DEVIATION 9 | 42 years STANDARD_DEVIATION 8.1 |
| Region of Enrollment United States | 22 participants | 20 participants | 15 participants | 16 participants | 73 participants |
| Sex: Female, Male Female | 1 Participants | 4 Participants | 4 Participants | 2 Participants | 11 Participants |
| Sex: Female, Male Male | 21 Participants | 16 Participants | 11 Participants | 14 Participants | 62 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk | EG002 affected / at risk | EG003 affected / at risk |
|---|---|---|---|---|
| deaths Total, all-cause mortality | — / — | — / — | — / — | — / — |
| other Total, other adverse events | 1 / 22 | 3 / 20 | 2 / 15 | 0 / 16 |
| serious Total, serious adverse events | 0 / 22 | 0 / 20 | 0 / 15 | 0 / 16 |
Outcome results
Primary
Cocaine Use as Assessed by the Treatment Effectiveness Score (TES), Which is the Total Number of Cocaine-negative Urines During Treatment
Time frame: 16 weeks
Population: All participants who received the first dose of study medication were included in this analysis.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| D-Amphetamine 60mg + Therapy | Cocaine Use as Assessed by the Treatment Effectiveness Score (TES), Which is the Total Number of Cocaine-negative Urines During Treatment | 9.25 number of cocaine negative urines | Standard Deviation 13.45 |
| Modafinil 400mg + Therapy | Cocaine Use as Assessed by the Treatment Effectiveness Score (TES), Which is the Total Number of Cocaine-negative Urines During Treatment | 6.09 number of cocaine negative urines | Standard Deviation 8.12 |
| Modafinil 200mg + D-Amphetamine 30mg + Therapy | Cocaine Use as Assessed by the Treatment Effectiveness Score (TES), Which is the Total Number of Cocaine-negative Urines During Treatment | 6 number of cocaine negative urines | Standard Deviation 7.73 |
| Placebo + Therapy | Cocaine Use as Assessed by the Treatment Effectiveness Score (TES), Which is the Total Number of Cocaine-negative Urines During Treatment | 4.91 number of cocaine negative urines | Standard Deviation 7.56 |
Primary
Retention as Indicated by the Number of Participants Who Completed 16 Weeks of Treatment
Time frame: 16 weeks
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| D-Amphetamine 60mg + Therapy | Retention as Indicated by the Number of Participants Who Completed 16 Weeks of Treatment | 7 participants |
| Modafinil 400mg + Therapy | Retention as Indicated by the Number of Participants Who Completed 16 Weeks of Treatment | 4 participants |
| Modafinil 200mg + D-Amphetamine 30mg + Therapy | Retention as Indicated by the Number of Participants Who Completed 16 Weeks of Treatment | 3 participants |
| Placebo + Therapy | Retention as Indicated by the Number of Participants Who Completed 16 Weeks of Treatment | 3 participants |
Primary
Retention as Indicated by the Number of Participants Who Remained in the Study
Time frame: 16 weeks
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| D-Amphetamine 60mg + Therapy | Retention as Indicated by the Number of Participants Who Remained in the Study | 7 participants |
| Modafinil 400mg + Therapy | Retention as Indicated by the Number of Participants Who Remained in the Study | 4 participants |
| Modafinil 200mg + D-Amphetamine 30mg + Therapy | Retention as Indicated by the Number of Participants Who Remained in the Study | 3 participants |
| Placebo + Therapy | Retention as Indicated by the Number of Participants Who Remained in the Study | 3 participants |
Secondary
Medication Compliance as Indicated by Percentage of Pills Taken According to Self-report
Time frame: 16 weeks
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| D-Amphetamine 60mg + Therapy | Medication Compliance as Indicated by Percentage of Pills Taken According to Self-report | 80.2 percentage of pills taken |
| Modafinil 400mg + Therapy | Medication Compliance as Indicated by Percentage of Pills Taken According to Self-report | 34.5 percentage of pills taken |
| Modafinil 200mg + D-Amphetamine 30mg + Therapy | Medication Compliance as Indicated by Percentage of Pills Taken According to Self-report | 65.8 percentage of pills taken |
| Placebo + Therapy | Medication Compliance as Indicated by Percentage of Pills Taken According to Self-report | 73.2 percentage of pills taken |
Secondary
Medication Compliance as Indicated by Percentage of Riboflavin-positive Urine Samples
Time frame: 16 weeks
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| D-Amphetamine 60mg + Therapy | Medication Compliance as Indicated by Percentage of Riboflavin-positive Urine Samples | 67.1 % of riboflavin-positive urine samples |
| Modafinil 400mg + Therapy | Medication Compliance as Indicated by Percentage of Riboflavin-positive Urine Samples | 70 % of riboflavin-positive urine samples |
| Modafinil 200mg + D-Amphetamine 30mg + Therapy | Medication Compliance as Indicated by Percentage of Riboflavin-positive Urine Samples | 76.8 % of riboflavin-positive urine samples |
| Placebo + Therapy | Medication Compliance as Indicated by Percentage of Riboflavin-positive Urine Samples | 66.7 % of riboflavin-positive urine samples |