Medications for Stopping Cocaine Dependence and Preventing Relapse

Study Overview
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Brief Summary
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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 identify subpopulations and baseline conditions that are most responsive to treatment for cocaine dependent individuals.

Detailed Description
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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. Motivational Interviewing (MI) is often effective when combined with drug treatment. Baseline condition (e.g., abstinence status) and population type (e.g., ethnicity and gender) often affect how an individual responds to treatment for drug dependence. The purpose of this study is to determine the influence of baseline status and population type on treatment response in cocaine dependent individuals. In addition, this study will examine how various cocaine abuse medications target different neuronal systems, withdrawal symptoms, and relapse to drug use. This study will take place in two phases. Phase I will last 4 weeks; participants will receive MI and undergo contingency-based urine tests in order to achieve the desired baseline condition. Phase II will last 12 weeks. Participants in Phase II will be randomly assigned to receive one of four treatments: 1) 50 mg naltrexone, 2) 800/200 mg levodopa/carbidopa, 3) 400 mg modafinil, or 4) placebo. During Phase II, all participants will receive psychotherapy and contingency management. Participants will complete urine drug screening tests 3 times each week. Follow-up study visits will occur between 3 and 6 months following Week 12, and will include objective and self-reported drug use.

Official Title
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Screening Medications for Cocaine Cessation and Relapse Prevention

Conditions
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Cocaine Abuse, Cocaine-Related Disorders

Intervention / Treatment
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* Drug: Modafinil
* Drug: Levodopa/Carbidopa
* Drug: Naltrexone HCl
* Drug: Placebo
* Behavioral: Motivational Interviewing (MI)
* Behavioral: Contingency management (CM)
* Behavioral: Cognitive-Behavioral Therapy (CBT)


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Meets DSM-IV criteria for current cocaine dependence Exclusion Criteria: Meet diagnostic criteria for other serious psychiatric symptoms and/or disorders that would interfere with participation in the treatment study (e.g., psychosis; mania; suicidal/ homicidal ideation) including other forms of drug dependence, nicotine and cannabis excepted. Medical conditions contraindicating naltrexone therapy (e.g., past history of opioid use in the 30 days prior to study entry or significant hepatocellular injury) Medical conditions contraindicating modafinil therapy (e.g., hypertension, seizures, arrhythmia, or coronary artery disease) Medical conditions contraindicating levodopa/carbidopa therapy (e.g., severe pulmonary/cardiovascular disease, narrow angle glaucoma, melanoma, history of peptic ulcer, or renal function impairment) Requires certain medications Current or recent treatment for substance use or other psychiatric condition On parole or probation that requires reports of drug use to officers of the court Pending incarceration Pregnant or breastfeeding Unable to read, write, or speak English Plans to leave the study area within 3 months of study entry

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 55 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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Accepts Healthy Volunteers

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: Modafinil plus MI, CM, and CBT<br>The modafinil dose began at 200 mg (day 1) and increased to the fixed dose of 200 mg twice daily (day 2) during the 12 weeks of Phase II. The motivational interviewing (MI) intervention consisted of two 1-h individual therapy sessions on the first and eighth day of Phase I. Contingency management (CM) is a voucher-based intervention. Subjects earned vouchers for cocaine abstinence (during Phase I) and medication compliance (during Phase II). Subjects received weekly, 1-h, individual Cognitive-Behavioral Therapy (CBT) sessions during Phase II. | Drug: Modafinil<br>* The modafinil dose began at 200 mg (day 1) and increased to the fixed dose of 200 mg twice daily (day 2) during the 12 weeks of Phase I.<br>* Other names: Provigil;Behavioral: Motivational Interviewing (MI)<br>* The primary goal of motivational interviewing (MI) was to assist patients in achieving initial abstinence by increasing motivation and commitment to change. The MI intervention consisted of two 1-h individual therapy sessions on the first and eighth day of Phase I. The client-centered, MI-style sessions focused on building motivation for change, exploring ambivalence, obtaining a commitment to change, making a plan for abstinence (Session 1), providing personalized feedback, reassessing commitment for change, and reevaluating the change plan (Session 2). Masters-level therapists were trained and supervised by the therapy supervisor (ALS), an expert in motivation-based therapies.<br>Behavioral: Contingency management (CM)<br>* Contingency management (CM) is a voucher-based intervention. Subjects earned vouchers for cocaine abstinence (during phase I) and medication compliance (during phase II).<br>Behavioral: Cognitive-Behavioral Therapy (CBT)<br>* Subjects received weekly, 1-h, individual Cognitive-Behavioral Therapy (CBT) sessions during Phase II. This therapy component focused on coping-skills training for resisting cocaine use in high-risk situations, based on relapse-prevention theory and manual-guided techniques. Therapy sessions were conducted by master's-level licensed professional counselors supervised by a licensed clinical psychologist, who monitored manual adherence and competency.<br>|
| Experimental: Levodopa/Carbidopa plus MI, CM, and CBT<br>Levodopa-carbidopa, in the sustained-release formulation (Sinemet CR), began at a dose of levodopa/carbidopa 400/100 mg (day 1) and increased to the fixed dose of 400/100 mg twice daily (day 2) during the 12 weeks of Phase II. The motivational interviewing (MI) intervention consisted of two 1-h individual therapy sessions on the first and eighth day of Phase I. Contingency management (CM) is a voucher-based intervention. Subjects earned vouchers for cocaine abstinence (during Phase I) and medication compliance (during Phase II). Subjects received weekly, 1-h, individual Cognitive-Behavioral Therapy (CBT) sessions during Phase II. | Drug: Levodopa/Carbidopa<br>* Levodopa-carbidopa, in the sustained-release formulation (Sinemet CR), began at a dose of levodopa/carbidopa 400/100 mg (day 1) and increased to the fixed dose of 400/100 mg twice daily (day 2) during the 12 weeks of Phase I.<br>* Other names: Simemet CR;Behavioral: Motivational Interviewing (MI)<br>* The primary goal of motivational interviewing (MI) was to assist patients in achieving initial abstinence by increasing motivation and commitment to change. The MI intervention consisted of two 1-h individual therapy sessions on the first and eighth day of Phase I. The client-centered, MI-style sessions focused on building motivation for change, exploring ambivalence, obtaining a commitment to change, making a plan for abstinence (Session 1), providing personalized feedback, reassessing commitment for change, and reevaluating the change plan (Session 2). Masters-level therapists were trained and supervised by the therapy supervisor (ALS), an expert in motivation-based therapies.<br>Behavioral: Contingency management (CM)<br>* Contingency management (CM) is a voucher-based intervention. Subjects earned vouchers for cocaine abstinence (during phase I) and medication compliance (during phase II).<br>Behavioral: Cognitive-Behavioral Therapy (CBT)<br>* Subjects received weekly, 1-h, individual Cognitive-Behavioral Therapy (CBT) sessions during Phase II. This therapy component focused on coping-skills training for resisting cocaine use in high-risk situations, based on relapse-prevention theory and manual-guided techniques. Therapy sessions were conducted by master's-level licensed professional counselors supervised by a licensed clinical psychologist, who monitored manual adherence and competency.<br>|
| Experimental: Naltrexone HCl plus MI, CM, and CBT<br>Naltrexone hydrochloride (HCl) doses began at 25 mg (day 1) and increased to the fixed dose of 25 mg twice daily (day 2) during the 12 weeks of Phase II. The motivational interviewing (MI) intervention consisted of two 1-h individual therapy sessions on the first and eighth day of Phase I. Contingency management (CM) is a voucher-based intervention. Subjects earned vouchers for cocaine abstinence (during Phase I) and medication compliance (during Phase II). Subjects received weekly, 1-h, individual Cognitive-Behavioral Therapy (CBT) sessions during Phase II. | Drug: Naltrexone HCl<br>* Naltrexone hydrochloride (HCl) doses began at 25 mg (day 1) and increased to the fixed dose of 25 mg twice daily (day 2) during the 12 weeks of Phase I.<br>* Other names: Naltrexon hydrochloride;Behavioral: Motivational Interviewing (MI)<br>* The primary goal of motivational interviewing (MI) was to assist patients in achieving initial abstinence by increasing motivation and commitment to change. The MI intervention consisted of two 1-h individual therapy sessions on the first and eighth day of Phase I. The client-centered, MI-style sessions focused on building motivation for change, exploring ambivalence, obtaining a commitment to change, making a plan for abstinence (Session 1), providing personalized feedback, reassessing commitment for change, and reevaluating the change plan (Session 2). Masters-level therapists were trained and supervised by the therapy supervisor (ALS), an expert in motivation-based therapies.<br>Behavioral: Contingency management (CM)<br>* Contingency management (CM) is a voucher-based intervention. Subjects earned vouchers for cocaine abstinence (during phase I) and medication compliance (during phase II).<br>Behavioral: Cognitive-Behavioral Therapy (CBT)<br>* Subjects received weekly, 1-h, individual Cognitive-Behavioral Therapy (CBT) sessions during Phase II. This therapy component focused on coping-skills training for resisting cocaine use in high-risk situations, based on relapse-prevention theory and manual-guided techniques. Therapy sessions were conducted by master's-level licensed professional counselors supervised by a licensed clinical psychologist, who monitored manual adherence and competency.<br>|
| Placebo Comparator: Placebo plus MI, CM, and CBT<br>Placebo capsules were identical in appearance to active drug capsules, and each contained 50 mg riboflavin for subsequent evaluation of medication compliance. The motivational interviewing (MI) intervention consisted of two 1-h individual therapy sessions on the first and eighth day of Phase I. Contingency management (CM) is a voucher-based intervention. Subjects earned vouchers for cocaine abstinence (during Phase I) and medication compliance (during Phase II). Subjects received weekly, 1-h, individual Cognitive-Behavioral Therapy (CBT) sessions during Phase II. | Drug: Placebo<br>* Placebo capsules were identical in appearance to active drug capsules, and each contained 50 mg riboflavin for subsequent evaluation of medication compliance.<br>Behavioral: Motivational Interviewing (MI)<br>* The primary goal of motivational interviewing (MI) was to assist patients in achieving initial abstinence by increasing motivation and commitment to change. The MI intervention consisted of two 1-h individual therapy sessions on the first and eighth day of Phase I. The client-centered, MI-style sessions focused on building motivation for change, exploring ambivalence, obtaining a commitment to change, making a plan for abstinence (Session 1), providing personalized feedback, reassessing commitment for change, and reevaluating the change plan (Session 2). Masters-level therapists were trained and supervised by the therapy supervisor (ALS), an expert in motivation-based therapies.<br>Behavioral: Contingency management (CM)<br>* Contingency management (CM) is a voucher-based intervention. Subjects earned vouchers for cocaine abstinence (during phase I) and medication compliance (during phase II).<br>Behavioral: Cognitive-Behavioral Therapy (CBT)<br>* Subjects received weekly, 1-h, individual Cognitive-Behavioral Therapy (CBT) sessions during Phase II. This therapy component focused on coping-skills training for resisting cocaine use in high-risk situations, based on relapse-prevention theory and manual-guided techniques. Therapy sessions were conducted by master's-level licensed professional counselors supervised by a licensed clinical psychologist, who monitored manual adherence and competency.<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Mean Percentage of Cocaine-positive Urines Over Course of 12 Week Treatment in Subgroup Achieving Abstinence at Baseline | Cocaine use was determined by assessing for the presence of benzoylecgonine in urine. | 3 times per week (Monday, Wednesday, and Friday) for 12 weeks | 
| Mean Percentage of Cocaine-positive Urines Over Course of 12 Week Treatment in Subgroup NOT Achieving Abstinence at Baseline | Cocaine use was determined by assessing for the presence of benzoylecgonine in urine. | 3 times per week (Monday, Wednesday, and Friday) for 12 weeks | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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cocaine, cocaine addiction, cocaine abuse, relapse prevention