Medications for Stopping Cocaine Dependence and Preventing Relapse

• Sponsor: The University of Texas Health Science Center, Houston (Other)
• Overall Status: Completed
• CT.gov ID: NCT00218023
• Collaborator: National Institute on Drug Abuse (NIDA) (NIH)
• Enrollment: 101
• Location: 1
• Arms: 4
• Duration (Months): 73
• Patients Per Site Per Month: 1.4

Study Details

Study Description

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.

Condition or Disease	Intervention/Treatment	Phase
Cocaine Abuse; Cocaine-Related Disorders	Drug: Modafinil; Drug: Levodopa/Carbidopa; Drug: Naltrexone HCl; Drug: Placebo; Behavioral: Motivational Interviewing (MI); Behavioral: Contingency management (CM); Behavioral: Cognitive-Behavioral Therapy (CBT)	Phase 2

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 Design

• Study Type: Interventional
• Actual Enrollment: 101 participants
• Allocation: Randomized
• Intervention Model: Parallel Assignment
• Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
• Primary Purpose: Treatment
• Official Title: Screening Medications for Cocaine Cessation and Relapse Prevention
• Study Start Date: Mar 1, 2006
• Actual Primary Completion Date: Apr 1, 2012
• Actual Study Completion Date: Apr 1, 2012

Arms and Interventions

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.	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 ; 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: 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.	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 ; 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.
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.	Drug: Placebo; Placebo capsules were identical in appearance to active drug capsules, and each contained 50 mg riboflavin for subsequent evaluation of medication compliance.; 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.

Outcome Measures

Primary Outcome Measures

1. 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.

2. 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.

Eligibility Criteria

Criteria

• Ages Eligible for Study: 18 Years to 55 Years
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: Yes

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

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	The University of Texas Health Science Center at Houston	Houston	Texas	United States	77030

Sponsors and Collaborators

• The University of Texas Health Science Center, Houston
• National Institute on Drug Abuse (NIDA)

Investigators

• Principal Investigator: Joy M Schmitz, PhD, University of Texas

Study Documents (Full-Text)

None provided.

More Information

Publications

None provided.

• Responsible Party: Joy Schmitz, Professor - Psy, Behavioral Science, The University of Texas Health Science Center, Houston
• ClinicalTrials.gov Identifier: NCT00218023
• Other Study ID Numbers: NIDA-09262-7; P50DA009262-07; DPMC
• First Posted: Sep 22, 2005
• Last Update Posted: Jun 9, 2017
• Last Verified: May 1, 2017

• 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
• Keywords provided by Joy Schmitz, Professor - Psy, Behavioral Science, The University of Texas Health Science Center, Houston: cocaine; cocaine addiction; cocaine abuse; relapse prevention
• Additional relevant MeSH terms: Recurrence; Cocaine-Related Disorders; Naltrexone; Levodopa; Carbidopa; Modafinil

Study Results

Participant Flow

Pre-assignment Detail	101 subjects were enrolled and began phase 1 (in phase 1, all enrolled subjects received the same intervention, motivational interviewing, which is described in the Interventions section). 81 completed phase 1, and 81 started phase 2, as described in the Period below. Subjects were assigned to the 4 arms at phase 2.

Arm/Group Title	Modafinil Plus MI, CM, and CBT	Levodopa/Carbidopa Plus MI, CM, and CBT	Naltrexone HCl Plus MI, CM, and CBT	Placebo Plus MI, CM, and CBT
Arm/Group Description	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, 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 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 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.
Period Title: Overall Study
STARTED	22	25	16	18
Received Drug or Placebo in Phase II	18	24	15	18
COMPLETED	9	10	6	11
NOT COMPLETED	13	15	10	7

Baseline Characteristics

Arm/Group Title	Modafinil Plus MI, CM, and CBT	Levodopa/Carbidopa Plus MI, CM, and CBT	Naltrexone HCl Plus MI, CM, and CBT	Placebo Plus MI, CM, and CBT	Total
Arm/Group Description	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, 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 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 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.	Total of all reporting groups
Overall Participants	22	25	16	18	81
Age (years) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [years]	43.64 (5.71)	40.66 (8.6)	42.08 (9.89)	42.29 (10.5)	42.16 (8.67)
Sex: Female, Male (Count of Participants)
Female	3 13.6%	6 24%	4 25%	1 5.6%	14 17.3%
Male	19 86.4%	19 76%	12 75%	17 94.4%	67 82.7%
Region of Enrollment (participants) [Number]
United States	22 100%	25 100%	16 100%	18 100%	81 100%

Outcome Measures

1. Primary Outcome

Title	Mean Percentage of Cocaine-positive Urines Over Course of 12 Week Treatment in Subgroup Achieving Abstinence at Baseline
Description	Cocaine use was determined by assessing for the presence of benzoylecgonine in urine.
Time Frame	3 times per week (Monday, Wednesday, and Friday) for 12 weeks

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Modafinil Plus MI, CM, and CBT	Levodopa/Carbidopa Plus MI, CM, and CBT	Naltrexone HCl Plus MI, CM, and CBT	Placebo Plus MI, CM, and CBT
Arm/Group Description	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, 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 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 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.
Measure Participants	8	8	9	10
Mean (Standard Error) [Mean % of cocaine-positive urines]	31 (0.238)	28 (0.20)	47 (0.261)	35 (0.186)

2. Primary Outcome

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

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Modafinil Plus MI, CM, and CBT	Levodopa/Carbidopa Plus MI, CM, and CBT	Naltrexone HCl Plus MI, CM, and CBT	Placebo Plus MI, CM, and CBT
Arm/Group Description	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, 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 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 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.
Measure Participants	14	17	7	8
Mean (Standard Error) [Mean % of cocaine-positive urines]	88 (0.029)	49 (0.254)	62 (0.219)	91 (0.016)

Adverse Events

Time Frame	The 12 weeks during which the drugs were administered (i.e., Phase II).
Arm/Group Title	Modafinil Plus MI, CM, and CBT		Levodopa/Carbidopa Plus MI, CM, and CBT		Naltrexone HCl Plus MI, CM, and CBT		Placebo Plus MI, CM, and CBT
Arm/Group Description	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, 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 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 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.
All Cause Mortality
	Modafinil Plus MI, CM, and CBT		Levodopa/Carbidopa Plus MI, CM, and CBT		Naltrexone HCl Plus MI, CM, and CBT		Placebo Plus MI, CM, and CBT
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	/ (NaN)		/ (NaN)		/ (NaN)		/ (NaN)
Serious Adverse Events
	Modafinil Plus MI, CM, and CBT		Levodopa/Carbidopa Plus MI, CM, and CBT		Naltrexone HCl Plus MI, CM, and CBT		Placebo Plus MI, CM, and CBT
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	1/22 (4.5%)		4/25 (16%)		1/16 (6.3%)		1/18 (5.6%)
Cardiac disorders
arrhythmia symptoms	0/22 (0%)	0	1/25 (4%)	1	0/16 (0%)	0	0/18 (0%)	0
Eye disorders
eye injury (torn conjunctiva)	0/22 (0%)	0	1/25 (4%)	1	0/16 (0%)	0	0/18 (0%)	0
General disorders
work-related traumatic injury to finger that required surgical repair	0/22 (0%)	0	0/25 (0%)	0	1/16 (6.3%)	1	0/18 (0%)	0
Hepatobiliary disorders
routine liver-function tests showed an increase from baseline in hepatic enzyme values	1/22 (4.5%)	1	0/25 (0%)	0	0/16 (0%)	0	0/18 (0%)	0
Psychiatric disorders
suicidal tendencies	0/22 (0%)	0	1/25 (4%)	1	0/16 (0%)	0	0/18 (0%)	0
Respiratory, thoracic and mediastinal disorders
respiratory infection	0/22 (0%)	0	1/25 (4%)	1	0/16 (0%)	0	0/18 (0%)	0
Vascular disorders
deep vein thrombosis	0/22 (0%)	0	0/25 (0%)	0	0/16 (0%)	0	1/18 (5.6%)	1
Other (Not Including Serious) Adverse Events
	Modafinil Plus MI, CM, and CBT		Levodopa/Carbidopa Plus MI, CM, and CBT		Naltrexone HCl Plus MI, CM, and CBT		Placebo Plus MI, CM, and CBT
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	0/22 (0%)		0/25 (0%)		0/16 (0%)		0/18 (0%)

Limitations/Caveats

The sample size was small; however, the main aim of the study was achieved (i.e., to evaluate the feasibility of using a two-phase abstinence induction paradigm to screen candidate medications for cocaine treatment).

More Information

Certain Agreements

All Principal Investigators ARE employed by the organization sponsoring the study.

There is NOT an agreement between Principal Investigators and the Sponsor (or its agents) that restricts the PI's rights to discuss or publish trial results after the trial is completed.