Cocaine-Related Disorders
Conditions
Keywords
cocaine
Brief summary
Despite years of active research, there are still no approved medications for the treatment of cocaine dependence. The purpose of this study is to determine the effectiveness of modafinil in treating cocaine-dependent individuals.
Detailed description
Modafinil is a glutamate-enhancing agent that blunts cocaine euphoria under controlled conditions. Due to its stimulant-like properties, modafinil is also likely to relieve severe cocaine withdrawal symptoms. In turn, this may lead to better clinical outcomes. The purpose of this study is to determine whether modafinil improves abstinence during early recovery from cocaine dependence. This 6-month, double-blind, placebo-controlled trial will enroll 210 participants with current DSM-IV diagnoses of cocaine dependence. Treatment will occur for 8 weeks. Participants will be randomly assigned to receive a single morning dose of low-dose modafinil (200 mg/day), high-dose modafinil (400 mg/day), or matching placebo tablets. In addition, each week participants will receive manual-guided cognitive behavioral therapy at the Treatment Research Center. At the end of the 8-week treatment period, modafinil or placebo will be abruptly discontinued. One week following, an end of medication evaluation will occur. In addition to this, two follow-up evaluations will take place 3 and 5 months after initial randomization. Efforts will be made to continue evaluation of subjects who decide to discontinue the modafinil treatment. Urine benzoylecgonine levels will be used to measure cocaine abstinence. Craving, withdrawal, retention, and adverse events will also be evaluated.
Interventions
DRUGLow Dose Modafinil
modafinil 200 mg/day
DRUGHigh Dose Modafinil
modafinil 400 mg/day
DRUGPlacebo
placebo 400 mg/day
Sponsors
National Institute on Drug Abuse (NIDA)
University of Pennsylvania
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 60 Years
Healthy volunteers
No
Inclusion criteria
* Male or female, aged 18 - 60 years; * Current DSM-IV diagnosis of cocaine dependence * Using at least $200 worth of cocaine within the past 30 days and having positive urine toxicology (BE) during screening; * Able to provide written informed consent and to comply with all study procedures; * Women must be surgically sterile, at least two years postmenopausal, or if of childbearing potential be using a medically accepted method of birth control and agree to continue use of this method for at least 30 days after the last dose of study drug (i.e. barrier method with spermicide, steroidal contraceptive \[oral and implanted, including Depo-Provera contraceptives must be used in conjunction with a barrier method\], or intrauterine device \[IUD\])
Exclusion criteria
* Currently dependent on any substance other than cocaine or nicotine * Neurological or psychiatric disorders, such as psychosis, bipolar illness, organic brain disease, dementia, or any diseases that require psychotropic medications * Serious medical illnesses, including but not limited to; uncontrolled hypertension, significant heart disease (including a history of myocardial infarction, angina, mitral valve prolapse, left ventricular hypertrophy, palpitations, and arrhythmia), hepatic disease, renal disease, or any serious, potentially life-threatening or progressive medical illness that may compromise patient safety or study conduct; * Received a drug with known potential for toxicity to a major organ system within the month prior to entering treatment including but not limited to; chemotherapeutic agents for neoplastic disease (i.e. methotrexate, vincristine, vinblastine, fluorouracil), agents used for parasitic infections, isoniazid, chlorambucil, dactinomycin, chloramphenicol, immunosuppressive and cytotoxic agents (i.e. cyclosporine, tacrolimus), indomethacin, protease inhibitors, amphotericin B, cephalosporins, aminoglycosides, interferon, and sulfonamides; * Clinically significant abnormal laboratory values * Has any disease of the gastrointestinal system, liver, or kidneys which could result in altered metabolism or excretion of the study medication (history of major gastrointestinal tract surgery, gastrectomy, gastrostomy, bowel resection, etc.) or history of chronic gastrointestinal disorders (ulcerative colitis, regional enteritis, or gastrointestinal bleeding); * Known hypersensitivity or allergy to modafinil or receiving chronic therapy with any medication that could interact adversely with one of the medications under study, including propranolol, phenytoin, warfarin and diazepam; * Currently taking any medication that could interact adversely with one of the medications under study, including propranolol, phenytoin, warfarin and diazepam * Took monoamine oxidase inhibitors (MAOI) within 30 days prior to randomization; * Taking or has taken an investigational drug within 60 days prior to enrollment * If female and of child-bearing capacity, tests positive on a urine pregnancy test, is lactating, has had three or more days of amenorrhea beyond expected menses at the time of the first dose of study medication, is contemplating pregnancy in the next 6 months, or is not using an effective contraceptive method; * Received therapy with any opiate-substitute (methadone, LAAM, buprenorphine) within 60 days of study enrollment.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Urine Toxicology for Cocaine | 3 weeks | Abstinent in the final 3 weeks of treatment |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Retention; Number of Evaluation Visits Attended | 8 weeks | Number of visits attended compared between the three conditions using anova |
| Cocaine Selective Severity Assessment (CSSA) Total Score | 8 weeks | Cocaine Selective Severity assessment (CSSA) total score has a range 0-126. Higher scores indicating greater severity of cocaine withdrawal obtained weekly. Groups compared using GEE model over 8 weeks of treatment. |
Countries
United States
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| Low Dose Modafinil Low Dose Modafinil
Modafinil Low Dose: modafinil 200 mg/day | 65 |
| High Dose Modafinil High Dose Modafinil
Modafinil High Dose: modafinil 400 mg/day | 70 |
| Placebo Placebo
Placebo: placebo 400 mg/day | 75 |
| Total | 210 |
Baseline characteristics
| Characteristic | High Dose Modafinil | Placebo | Low Dose Modafinil | Total |
|---|---|---|---|---|
| Age, Categorical <=18 years | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Age, Categorical >=65 years | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Age, Categorical Between 18 and 65 years | 70 Participants | 75 Participants | 65 Participants | 210 Participants |
| Age, Continuous | 43.64 years STANDARD_DEVIATION 7.7 | 42.46 years STANDARD_DEVIATION 7.5 | 41.72 years STANDARD_DEVIATION 6.9 | 42.64 years STANDARD_DEVIATION 8.7 |
| Region of Enrollment United States | 70 participants | 75 participants | 65 participants | 210 participants |
| Sex: Female, Male Female | 18 Participants | 19 Participants | 18 Participants | 55 Participants |
| Sex: Female, Male Male | 52 Participants | 56 Participants | 47 Participants | 155 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk | EG002 affected / at risk |
|---|---|---|---|
| deaths Total, all-cause mortality | — / — | — / — | — / — |
| other Total, other adverse events | 63 / 70 | 62 / 75 | 50 / 65 |
| serious Total, serious adverse events | 1 / 70 | 0 / 75 | 0 / 65 |
Outcome results
Primary
Urine Toxicology for Cocaine
Abstinent in the final 3 weeks of treatment
Time frame: 3 weeks
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Low Dose Modafinil | Urine Toxicology for Cocaine | 3 Participants |
| High Dose Modafinil | Urine Toxicology for Cocaine | 8 Participants |
| Placebo | Urine Toxicology for Cocaine | 3 Participants |
Secondary
Cocaine Selective Severity Assessment (CSSA) Total Score
Cocaine Selective Severity assessment (CSSA) total score has a range 0-126. Higher scores indicating greater severity of cocaine withdrawal obtained weekly. Groups compared using GEE model over 8 weeks of treatment.
Time frame: 8 weeks
Population: patients exposed to low dose and high dose modafinil
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Low Dose Modafinil | Cocaine Selective Severity Assessment (CSSA) Total Score | 12.89 units on a scale | Standard Deviation 11.7 |
| High Dose Modafinil | Cocaine Selective Severity Assessment (CSSA) Total Score | 15.04 units on a scale | Standard Deviation 13.52 |
| Placebo | Cocaine Selective Severity Assessment (CSSA) Total Score | 15.2 units on a scale | Standard Deviation 14.32 |
Secondary
Retention; Number of Evaluation Visits Attended
Number of visits attended compared between the three conditions using anova
Time frame: 8 weeks
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Low Dose Modafinil | Retention; Number of Evaluation Visits Attended | 16.8 number of evaluation sessions attended | Standard Deviation 7.1 |
| High Dose Modafinil | Retention; Number of Evaluation Visits Attended | 16.5 number of evaluation sessions attended | Standard Deviation 6.7 |
| Placebo | Retention; Number of Evaluation Visits Attended | 14.3 number of evaluation sessions attended | Standard Deviation 7.1 |