Cognitive Enhancement and Relapse Prevention in Cocaine Addiction

Study Overview
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Brief Summary
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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
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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: 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. Determine if DCS administration relative to placebo facilitates CBT-related decreases in the behavioral and neural response to conditioned cocaine cues.

Official Title
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The Clinical and Neural Response of Cocaine Addicts to Combination Treatment With a Cognitive Enhancer and Extinction-Based Psychotherapy

Conditions
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Cocaine Addiction

Intervention / Treatment
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* Drug: Seromycin (D-cycloserine, DCS)
* Drug: Placebo
* Behavioral: Computerized Cognitive Behavioral Therapy


Participation Criteria
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Eligibility Criteria
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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.

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 65 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Triple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: DCS and Cognitive Behavioral Therapy<br>Subjects will receive 250 mg of Seromycin or D-cycloserine (DCS) prior to computerized cognitive behavioral therapy. | Drug: Seromycin (D-cycloserine, DCS)<br>* 250 mg DCS once weekly for 4 weeks prior to the initiation of a Computerized Cognitive Behavioral Therapy (CBT) session for drug relapse intervention.<br>* Other names: D-cycloserine, DCS;Behavioral: Computerized Cognitive Behavioral Therapy<br>* All participants received Computerized Cognitive Behavioral Therapy sessions 3 times per week for 4 weeks as a drug relapse intervention.<br>|
| Placebo Comparator: Placebo and Cognitive Behavioral Therapy<br>Subjects will receive a 250 mg identical looking placebo pill prior to computerized cognitive behavioral therapy. | Drug: Placebo<br>* 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.<br>Behavioral: Computerized Cognitive Behavioral Therapy<br>* All participants received Computerized Cognitive Behavioral Therapy sessions 3 times per week for 4 weeks as a drug relapse intervention.<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Drug Abstinence During Treatment and at Follow up Visits | Percentage of the overall number of drug abstinences of participants measured by urine drug testing | 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 | 
| Treatment Retention - Number of Visits During Treatment | Number of treatment visits attended prior to discontinuation of treatment | Treatment sessions included 3 visits per week for 4 weeks | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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cocaine dependence, relapse prevention, computerized cognitive behavioral therapy (CBT), D-cycloserine (DCS)