Medications for Stopping Cocaine Dependence and Preventing Relapse

Screening Medications for Cocaine Cessation and Relapse Prevention

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.

Study Overview

• Status: Completed
• Conditions: Cocaine-Related Disorders; Cocaine Abuse
• Intervention / Treatment: Drug: Modafinil; Behavioral: Motivational Interviewing (MI); Behavioral: Contingency management (CM); Behavioral: Cognitive-Behavioral Therapy (CBT); Drug: Levodopa/Carbidopa; Drug: Naltrexone HCl; Drug: Placebo

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. 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.

• Study Type: Interventional
• Enrollment (Actual): 101
• Phase: Phase 2

Contacts and Locations

Study Locations

• United States
  • Texas
    • Houston, Texas, United States, 77030
      • The University of Texas Health Science Center at Houston

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 55 years (Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

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

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Quadruple

Number of Arms

4

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Modafinil plus MI, CM, and CBT; 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; 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.; Other Names: Provigil; Behavioral: Motivational Interviewing (MI); 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.; Behavioral: Contingency management (CM); Contingency management (CM) is a voucher-based intervention. Subjects earned vouchers for cocaine abstinence (during phase I) and medication compliance (during phase II).; Behavioral: Cognitive-Behavioral Therapy (CBT); 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.
Experimental: Levodopa/Carbidopa plus MI, CM, and CBT; 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.	Behavioral: Motivational Interviewing (MI); 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.; Behavioral: Contingency management (CM); Contingency management (CM) is a voucher-based intervention. Subjects earned vouchers for cocaine abstinence (during phase I) and medication compliance (during phase II).; Behavioral: Cognitive-Behavioral Therapy (CBT); 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.; Drug: Levodopa/Carbidopa; 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.; Other Names: Simemet CR
Experimental: Naltrexone HCl plus MI, CM, and CBT; 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.	Behavioral: Motivational Interviewing (MI); 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.; Behavioral: Contingency management (CM); Contingency management (CM) is a voucher-based intervention. Subjects earned vouchers for cocaine abstinence (during phase I) and medication compliance (during phase II).; Behavioral: Cognitive-Behavioral Therapy (CBT); 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.; Drug: Naltrexone HCl; 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.; Other Names: Naltrexon hydrochloride
Placebo Comparator: Placebo plus MI, CM, and CBT; 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.	Behavioral: Motivational Interviewing (MI); 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.; Behavioral: Contingency management (CM); Contingency management (CM) is a voucher-based intervention. Subjects earned vouchers for cocaine abstinence (during phase I) and medication compliance (during phase II).; Behavioral: Cognitive-Behavioral Therapy (CBT); 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.; Drug: Placebo; Placebo capsules were identical in appearance to active drug capsules, and each contained 50 mg riboflavin for subsequent evaluation of medication compliance.

What is the study measuring?

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

Collaborators and Investigators

• Sponsor: The University of Texas Health Science Center, Houston
• Collaborators: National Institute on Drug Abuse (NIDA)
• Investigators: Principal Investigator: Joy M Schmitz, PhD, University of Texas

Publications and helpful links

General Publications

• Schmitz JM, Green CE, Stotts AL, Lindsay JA, Rathnayaka NS, Grabowski J, Moeller FG. A two-phased screening paradigm for evaluating candidate medications for cocaine cessation or relapse prevention: modafinil, levodopa-carbidopa, naltrexone. Drug Alcohol Depend. 2014 Mar 1;136:100-7. doi: 10.1016/j.drugalcdep.2013.12.015. Epub 2014 Jan 3.

Study record dates

Study Major Dates

• Study Start: March 1, 2006
• Primary Completion (Actual): April 1, 2012
• Study Completion (Actual): April 1, 2012

Study Registration Dates

• First Submitted: September 16, 2005
• First Submitted That Met QC Criteria: September 16, 2005
• First Posted (Estimate): September 22, 2005

Study Record Updates

• Last Update Posted (Actual): June 9, 2017
• Last Update Submitted That Met QC Criteria: May 11, 2017
• Last Verified: May 1, 2017

More Information

Terms related to this study

• Keywords: relapse prevention; cocaine; cocaine addiction; cocaine abuse
• Additional Relevant MeSH Terms: Mental Disorders; Chemically-Induced Disorders; Pathologic Processes; Substance-Related Disorders; Disease Attributes; Recurrence; Cocaine-Related Disorders; Physiological Effects of Drugs; Neurotransmitter Agents; Molecular Mechanisms of Pharmacological Action; Peripheral Nervous System Agents; Enzyme Inhibitors; Sensory System Agents; Dopamine Agents; Narcotic Antagonists; Cytochrome P-450 Enzyme Inducers; Cytochrome P-450 CYP3A Inducers; Alcohol Deterrents; Central Nervous System Stimulants; Antiparkinson Agents; Anti-Dyskinesia Agents; Aromatic Amino Acid Decarboxylase Inhibitors; Wakefulness-Promoting Agents; Naltrexone; Levodopa; Carbidopa; Modafinil
• Other Study ID Numbers: NIDA-09262-7; DPMC (Other Identifier: NIDA); P50DA009262-07 (U.S. NIH Grant/Contract)

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No
• product manufactured in and exported from the U.S.: No