Medications for Stopping Cocaine Dependence and Preventing Relapse

Phase 2

Completed

Conditions: Cocaine Abuse
Cocaine-Related Disorders

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

Registration Number: NCT00218023

Lead Sponsor: The University of Texas Health Science Center, Houston

Brief Summary: 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: 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.

Recruitment & Eligibility

Status: COMPLETED

Sex: All

Target Recruitment: 101

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 & Design

Study Type: INTERVENTIONAL

Study Design: PARALLEL

Arm && Interventions

Group	Intervention	Description
Modafinil plus MI, CM, and CBT	Contingency management (CM)	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.
Modafinil plus MI, CM, and CBT	Cognitive-Behavioral Therapy (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.
Modafinil plus MI, CM, and CBT	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 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.
Modafinil plus MI, CM, and CBT	Motivational Interviewing (MI)	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.
Levodopa/Carbidopa plus MI, CM, and CBT	Motivational Interviewing (MI)	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.
Levodopa/Carbidopa plus MI, CM, and CBT	Contingency management (CM)	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.
Levodopa/Carbidopa plus MI, CM, and CBT	Cognitive-Behavioral Therapy (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.
Naltrexone HCl plus MI, CM, and CBT	Motivational Interviewing (MI)	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.
Naltrexone HCl plus MI, CM, and CBT	Contingency management (CM)	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.
Naltrexone HCl plus MI, CM, and CBT	Cognitive-Behavioral Therapy (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.
Placebo plus MI, CM, and CBT	Placebo	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.
Placebo plus MI, CM, and CBT	Motivational Interviewing (MI)	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.
Placebo plus MI, CM, and CBT	Contingency management (CM)	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.
Placebo plus MI, CM, and CBT	Cognitive-Behavioral Therapy (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.
Levodopa/Carbidopa plus MI, CM, and CBT	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 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.
Naltrexone HCl plus MI, CM, and CBT	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 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.

Primary Outcome Measures

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

Secondary Outcome Measures