Modafinil Treatment for Cocaine-Dependent Individuals

Study Overview
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Brief Summary
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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
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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.

Official Title
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A Double-Blind, Placebo-Controlled Study of Modafinil for Cocaine Dependence

Conditions
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Cocaine-Related Disorders

Intervention / Treatment
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* Drug: Low Dose Modafinil
* Drug: High Dose Modafinil
* Drug: Placebo


Participation Criteria
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Eligibility Criteria
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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.

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 60 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: Low Dose Modafinil<br>Low Dose Modafinil 200 mg daily | Drug: Low Dose Modafinil<br>* modafinil 200 mg/day<br>* Other names: Provigil;|
| Experimental: High Dose Modafinil<br>High dose modafinil 400 mg daily | Drug: High Dose Modafinil<br>* modafinil 400 mg/day<br>* Other names: Provigil;|
| Placebo Comparator: Placebo<br>Placebo | Drug: Placebo<br>* placebo 400 mg/day<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Urine Toxicology for Cocaine | Abstinent in the final 3 weeks of treatment | 3 weeks | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Retention; Number of Evaluation Visits Attended | Number of visits attended compared between the three conditions using anova | 8 weeks | 
| 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. | 8 weeks | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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cocaine