Cocaine Addiction
Conditions
Keywords
cocaine dependence, relapse prevention, computerized cognitive behavioral therapy (CBT), D-cycloserine (DCS)
Brief summary
For this project, the investigators are interested in exploring a new way to extend and maintain drug abstinence in people who are addicted to crack cocaine. This study will combine a medication called D-Cycloserine (DCS) and weekly cognitive behavioral therapy (CBT) to assess whether the combination will enhance people's ability to stay clean (drug free) for longer periods of time. One of the greatest risks for drug relapse is drug craving. Oftentimes drug craving occurs when a person is confronted with stressors and reminders of past drug use behavior. DCS has been shown to enhance the learning of new information. By administering DCS prior to learning new techniques such as how to cope with drug craving and drug-use reminders, it is possible that patients can be more successful at living a drug free life for a longer period of time. In addition to exploring this model behaviorally, the investigators will explore changes that may occur in the brain before and after the therapy/medication intervention. A technique called MRI (Magnetic Resonance Imaging) will be used to identify areas of the brain that are being activated during an attention task. Areas of neural activation will be assessed at study entry, end of therapy (4-week endpoint) and one month following completion of the treatment program.
Detailed description
Primary Hypothesis: Enhancing glutamatergic neurotransmission with DCS facilitates CBT-related relapse prevention by potentiating the behavioral and neural representation of the diminished drug motivation associated with cocaine cues. Specific Aims: 1. Determine if the short-term oral administration of DCS relative to placebo prior to CBT sessions facilitates cocaine abstinence and functional recovery, and reduces cocaine craving in treatment-seeking cocaine addicts. 2. Determine if DCS administration relative to placebo facilitates CBT-related decreases in the behavioral and neural response to conditioned cocaine cues.
Interventions
DRUGSeromycin (D-cycloserine, DCS)
250 mg DCS once weekly for 4 weeks prior to the initiation of a Computerized Cognitive Behavioral Therapy (CBT) session for drug relapse intervention.
DRUGPlacebo
Placebo identical looking to the 250 mg DCS once weekly for 4 weeks prior to the initiation of a Computerized Cognitive Behavioral Therapy (CBT) session for drug relapse intervention.
All participants received Computerized Cognitive Behavioral Therapy sessions 3 times per week for 4 weeks as a drug relapse intervention.
Sponsors
National Institute on Drug Abuse (NIDA)
University of Arkansas
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
TRIPLE (Subject, Investigator, Outcomes Assessor)
Eligibility
Sex/Gender
ALL
Age
18 Years to 65 Years
Healthy volunteers
No
Inclusion criteria
* Eligible subjects must be cocaine-dependent persons between 18 and 65 years
Exclusion criteria
* Any current Axis-I psychiatric diagnosis other than cocaine or alcohol dependence or nicotine use * Any current or prior neurological disease, history of a major medical illness, or current use of psychotropic medications * Positive history of loss of consciousness of greater than 10 min * Significant current or prior cardiovascular disease (hypertension, arrhythmias) that is not medically stable * History of hospitalization within the previous six months for a medical illness * Deafness, blindness or other significant sensory impairment. * Contraindications for D-cycloserine and magnetic resonance imaging.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Drug Abstinence During Treatment and at Follow up Visits | Participants provided urine samples for drug testing during treatment which occurred 3 times per week for 4 weeks, at the end of treatment, and at a 1 and 2 month follow up visit | Percentage of the overall number of drug abstinences of participants measured by urine drug testing |
| Treatment Retention - Number of Visits During Treatment | Treatment sessions included 3 visits per week for 4 weeks | Number of treatment visits attended prior to discontinuation of treatment |
Countries
United States
Participant flow
Recruitment details
Recruitment included outpatient and inpatient alcohol and drug abuse clinics, self-referrals, flyers in public places, and advertisements in newspapers. Recruitment started June 2010 and ended September 2011.
Pre-assignment details
Enrolled participants could have been excluded due to other drug dependencies, loss of consciousness \> 10 min, neurologic disorder, severe hepatic insufficiency, significant cardiovascular disease, current psychiatric disorder, current medical illness, sensory impairment, positive pregnancy test.
Participants by arm
| Arm | Count |
|---|---|
| DCS and Cognitive Behavioral Therapy Subjects will receive 250 mg of Seromycin or D-cycloserine (DCS) prior to computerized cognitive behavioral therapy.
Seromycin (D-cycloserine, DCS) : 250 mg DCS once weekly for 4 weeks prior to the initiation of a Computerized Cognitive Behavioral Therapy (CBT) session for drug relapse intervention. | 29 |
| Placebo and Cognitive Behavioral Therapy Subjects will receive a 250 mg identical looking placebo pill prior to computerized cognitive behavioral therapy.
Placebo : Placebo identical looking to the 250 mg DCS once weekly for 4 weeks prior to the initiation of a Computerized Cognitive Behavioral Therapy (CBT) session for drug relapse intervention. | 30 |
| Total | 59 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 |
|---|---|---|---|
| Overall Study | Lost to Follow-up | 17 | 19 |
| Overall Study | participation in other tx study | 1 | 0 |
| Overall Study | Withdrawal by Subject | 1 | 0 |
Baseline characteristics
| Characteristic | Placebo and Cognitive Behavioral Therapy | DCS and Cognitive Behavioral Therapy | Total |
|---|---|---|---|
| Age, Categorical <=18 years | 0 Participants | 0 Participants | 0 Participants |
| Age, Categorical >=65 years | 0 Participants | 0 Participants | 0 Participants |
| Age, Categorical Between 18 and 65 years | 30 Participants | 29 Participants | 59 Participants |
| Age Continuous | 45 years STANDARD_DEVIATION 9.13 | 44 years STANDARD_DEVIATION 6.67 | 44 years STANDARD_DEVIATION 7.97 |
| Region of Enrollment United States | 30 participants | 29 participants | 59 participants |
| Sex: Female, Male Female | 4 Participants | 7 Participants | 11 Participants |
| Sex: Female, Male Male | 26 Participants | 22 Participants | 48 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | — / — | — / — |
| other Total, other adverse events | 3 / 29 | 2 / 30 |
| serious Total, serious adverse events | 0 / 29 | 0 / 30 |
Outcome results
Primary
Drug Abstinence During Treatment and at Follow up Visits
Percentage of the overall number of drug abstinences of participants measured by urine drug testing
Time frame: Participants provided urine samples for drug testing during treatment which occurred 3 times per week for 4 weeks, at the end of treatment, and at a 1 and 2 month follow up visit
Population: Total possible urine samples = 225 per arm. Not all participants stayed in treatment, therefore the total units analyzed will not match the total possible.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| DCS and Cognitive Behavioral Therapy | Drug Abstinence During Treatment and at Follow up Visits | 12 percentage of drug abstinences |
| Placebo and Cognitive Behavioral Therapy | Drug Abstinence During Treatment and at Follow up Visits | 25 percentage of drug abstinences |
Primary
Treatment Retention - Number of Visits During Treatment
Number of treatment visits attended prior to discontinuation of treatment
Time frame: Treatment sessions included 3 visits per week for 4 weeks
Population: Total possible sessions attended = 180 per arm. Some participants did not complete all sessions, therefore the units analyzed will not match the total possible.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| DCS and Cognitive Behavioral Therapy | Treatment Retention - Number of Visits During Treatment | 10 visits | Standard Deviation 3 |
| Placebo and Cognitive Behavioral Therapy | Treatment Retention - Number of Visits During Treatment | 10 visits | Standard Deviation 3 |