Modafinil Treatment for Cocaine-Dependent Individuals

Phase 2

Completed

Conditions: Cocaine-Related Disorders

Interventions: Drug: High Dose Modafinil
Drug: Placebo
Drug: Low Dose Modafinil

Registration Number: NCT00129285

Lead Sponsor: University of Pennsylvania

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.

Recruitment & Eligibility

Status: COMPLETED

Sex: All

Target Recruitment: 210

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.

Study & Design

Study Type: INTERVENTIONAL

Study Design: PARALLEL

Arm && Interventions

Group	Intervention	Description
High Dose Modafinil	High Dose Modafinil	High dose modafinil 400 mg daily
Placebo	Placebo	Placebo
Low Dose Modafinil	Low Dose Modafinil	Low Dose Modafinil 200 mg daily

Primary Outcome Measures

Name	Time	Method
Urine Toxicology for Cocaine	3 weeks	Abstinent in the final 3 weeks of treatment

Secondary Outcome Measures

Name	Time	Method
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.
Retention; Number of Evaluation Visits Attended	8 weeks	Number of visits attended compared between the three conditions using anova