Carbidopa/Levodopa Combined With Behavioral Therapy for the Treatment of Cocaine Dependence

NCT00713583 | Completed Phase 2 Results DMC FDA Drug

• 3 other identifiers: 1R01DA023608-01R01DA023608-01DPMCDA
• Study Type: interventional
• Target: 85
• Locations: 1 country
• Sites: 1

Brief Summary

Cocaine dependence is a major public health problem and the development of a treatment for this disorder is a priority. To date, treatment interventions based on positive incentive principles have shown the strongest effects for improving substance use outcomes. One such example is contingency management (CM) interventions in which nondrug rewards are used to compete with cocaine. Recent evidence suggests that certain medications improve response to CM interventions, particularly agents that target dopamine reward systems in the brain. A promising dopamine-enhancing medication is levodopa. The study team has observed the strongest effects of levodopa when the medication is administered in the context of CM therapy, perhaps through mechanisms that enhance reward saliency. The proposed study is designed to further evaluate this promising treatment approach. Cocaine dependent outpatients will participate in a randomized, 2-group (levodopa vs. placebo), double-blind clinical trial. CM will be behavioral therapy platform for both treatment groups. The study will test the primary hypothesis that CM+levodopa will be more effective than CM+placebo in reducing cocaine use. This study is expected to validate the usefulness of a new behavioral-pharmacological treatment approach for cocaine dependence.

Conditions

Cocaine Dependence

Keywords

Cocaine, levodopa, contingency management

Outcome Measures

Primary Outcomes (1)

• Confirmed Abstinence From Cocaine as Assessed by Treatment Effectiveness Score (TES)

  The Treatment Effectiveness Score (TES) is the number of cocaine-negative urines collected out of the total scheduled urine tests for the 12-week trial (36 total scheduled urine tests per participant). The mean number of cocaine-negative urines over all time points is reported in this outcome measure.

  12 weeks of treatment

Study Arms (2)

Levodopa pharmacotherapy

EXPERIMENTAL

Levodopa pharmacotherapy (800mg levodopa and 200mg carbidopa per day), cognitive behavioral therapy (CBT), and contingency management (CM).

Drug: levodopa; Behavioral: Cognitive Behavioral Therapy; Behavioral: Contingency Management

Placebo

PLACEBO COMPARATOR

Placebo, cognitive behavioral therapy (CBT), and contingency management (CM).

Drug: Placebo; Behavioral: Cognitive Behavioral Therapy; Behavioral: Contingency Management

Interventions

levodopa DRUG

800mg levodopa and 200mg carbidopa per day

Also known as: Sinemet

Levodopa pharmacotherapy

Placebo DRUG

Placebo

Placebo

Cognitive Behavioral Therapy BEHAVIORAL

Participants received individual cognitive behavioral therapy (CBT) in 50-minute weekly sessions. These sessions were manual-driven and based on the relapse prevention model proposed by Marlatt and Gordon (1985). Trained masters-level therapists, under the supervision of senior therapists and the principal investigator, worked with participants to teach them how to recognize and cope with risky situations that could influence their cocaine use through self-monitoring of situational craving and drug use stimuli, coping skills training, and lifestyle modifications.

Levodopa pharmacotherapy; Placebo

Contingency Management BEHAVIORAL

An abstinence-based contingency management (CM) procedure was used. Participants earned vouchers according to the reward schedule recommended by Budney and Higgins (1998), beginning at $2.50 for the first cocaine-negative urine. For each consecutive cocaine-negative urine, voucher values increased by $1.25 with a $10 bonus given for provision of three consecutive cocaine-negative urines within a week. A cocaine-positive urine or failure to provide a scheduled urine sample resulted in a reset of the schedule to the initial value of $2.50. After provision of five negative urines, the voucher returned to the value prior to the reset. Participants were able to redeem their vouchers for small amounts of cash (≤$25) or gift cards for goods and services.

Levodopa pharmacotherapy; Placebo

Eligibility Criteria

• Age: 18 Years - 60 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64)

You may qualify if:

• between 18 and 60 years of age
• meet Diagnostic and Statistical Manual of Mental Disorders, 4th. Edition (DSM-IV) criteria for current cocaine dependence.
• be in acceptable health on the basis of interview, medical history and physical exam.

You may not qualify if:

• current DSM-IV diagnosis of any psychoactive substance dependence other than cocaine, marijuana, or nicotine.
• have a DSM-IV axis I psychiatric disorder or neurological disease or disorder requiring ongoing treatment and/or making study participation unsafe.
• have significant current suicidal or homicidal ideation.
• have medical conditions contraindicating levodopa/carbidopa pharmacotherapy. Conditions include severe pulmonary disease (bronchial asthma, emphysema), cardiovascular disease (severe or history of myocardial infarction with residual arrhythmias), narrow angle glaucoma, melanoma, history of peptic ulcer, renal function impairment.
• taking medications known to have significant drug interactions with levodopa/carbidopa (e.g., monoamine oxidase (MAO) inhibitors, anticonvulsants, haloperidol, phenothiazines, selegiline, anesthetics).
• currently or recently (last 3 months) treated for substance use or another psychiatric condition.
• having conditions of probation or parole requiring reports of drug use to officers of the court.
• impending incarceration.
• pregnant or nursing for female patients.
• inability to read, write, or speak English.

Sponsors & Collaborators

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

Study Sites (1)

The University of Texas Health Science Center at Houston

Houston, Texas, 77030, United States

Location

MeSH Terms

Conditions

Cocaine-Related Disorders

Interventions

Levodopa; carbidopa, levodopa drug combination; Cognitive Behavioral Therapy

Condition Hierarchy (Ancestors)

Substance-Related Disorders; Chemically-Induced Disorders; Mental Disorders

Intervention Hierarchy (Ancestors)

Dihydroxyphenylalanine; Catecholamines; Amines; Organic Chemicals; Catechols; Phenols; Benzene Derivatives; Hydrocarbons, Aromatic; Hydrocarbons, Cyclic; Hydrocarbons; Phenylalanine; Amino Acids, Aromatic; Amino Acids, Cyclic; Amino Acids; Amino Acids, Peptides, and Proteins; Tyrosine; Behavior Therapy; Psychotherapy; Behavioral Disciplines and Activities

Limitations and Caveats

Lower than expected rates of retention and medication compliance likely reduced the statistical power of the study for estimating treatment effects of the medication intervention.

Results Point of Contact

• Title: Joy M. Schmitz, PhD
• Organization: The University of Texas Health Science Center at Houston

Joy.M.Schmitz@uth.tmc.edu

(713) 486-2867

Study Officials

• Joy M Schmitz, PhD

  University of Texas at Houston

  PRINCIPAL INVESTIGATOR

Publication Agreements

• PI is Sponsor Employee: Yes

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: QUADRUPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR, OUTCOMES ASSESSOR
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Professor - Psychiatry, Behavioral Sciences

Study Record Dates

• First Submitted: July 9, 2008
• First Posted: July 11, 2008
• Study Start: January 1, 2008
• Primary Completion: December 1, 2011
• Study Completion: December 1, 2011
• Last Updated: April 23, 2018
• Results First Posted: March 19, 2018

Record last verified: 2018-03

Locations

US (1)