Cocaine Dependence
Conditions
Keywords
Cocaine, levodopa, contingency management
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.
Interventions
DRUGlevodopa
800mg levodopa and 200mg carbidopa per day
DRUGPlacebo
Placebo
BEHAVIORALCognitive Behavioral Therapy
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.
BEHAVIORALContingency Management
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.
Sponsors
National Institute on Drug Abuse (NIDA)
The University of Texas Health Science Center, Houston
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
QUADRUPLE (Subject, Caregiver, Investigator, Outcomes Assessor)
Eligibility
Sex/Gender
ALL
Age
18 Years to 60 Years
Healthy volunteers
No
Inclusion criteria
* 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.
Exclusion criteria
* 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.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Confirmed Abstinence From Cocaine as Assessed by Treatment Effectiveness Score (TES) | 12 weeks of treatment | 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. |
Countries
United States
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| Levodopa Pharmacotherapy Levodopa pharmacotherapy, cognitive behavioral therapy (CBT), and contingency management (CM). | 45 |
| Placebo Placebo, cognitive behavioral therapy (CBT), and contingency management (CM). | 40 |
| Total | 85 |
Baseline characteristics
| Characteristic | Levodopa Pharmacotherapy | Placebo | Total |
|---|---|---|---|
| Age, Continuous | 46 years STANDARD_DEVIATION 7.9 | 45 years STANDARD_DEVIATION 9.2 | 46 years STANDARD_DEVIATION 8.5 |
| Region of Enrollment United States | 45 Participants | 40 Participants | 85 Participants |
| Sex: Female, Male Female | 10 Participants | 5 Participants | 15 Participants |
| Sex: Female, Male Male | 35 Participants | 35 Participants | 70 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | — / — | — / — |
| other Total, other adverse events | 0 / 45 | 0 / 40 |
| serious Total, serious adverse events | 6 / 45 | 3 / 40 |
Outcome results
Primary
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.
Time frame: 12 weeks of treatment
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Levodopa Pharmacotherapy | Confirmed Abstinence From Cocaine as Assessed by Treatment Effectiveness Score (TES) | 7 cocaine-negative urines | Standard Deviation 11.7 |
| Placebo | Confirmed Abstinence From Cocaine as Assessed by Treatment Effectiveness Score (TES) | 9 cocaine-negative urines | Standard Deviation 12.6 |