VIVITROL as a Treatment for Cocaine and Alcohol Dependence

Study Overview
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Brief Summary
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To evaluate the efficacy of VIVITROL (naltrexone for extended-release injectable suspension) for the treatment of co-occurring cocaine and alcohol dependence

Detailed Description
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This is a Phase II double-blind randomized controlled clinical pilot study. The exploratory objectives in the proposed study will be examined with a 2-group design to assess the efficacy of naltrexone extended-release injectable suspension (VIVITROL™) as compared to placebo. Safety measures will be collected weekly through medical management (MM) by medical practitioners, including adverse events and concomitant meds. The psychosocial treatment will be Cognitive Behavioral Coping Skills Therapy (CBT). Subjects will be 80 men and women with current DSM-IV diagnoses of alcohol dependence and cocaine dependence that will be randomized to receive either VIVITROL or placebo (40 subjects per group). All subjects will receive weekly sessions of CBT and MM. The study length for each subject is comprised of 1-3 weeks of screening, an 8-week double-blind, placebo-controlled trial with MM and CBT (medication phase), and an end of medication visit. Primary Exploratory Objectives: To compare medication groups' rates of cocaine abstinence, as determined by urine assay for benzoylecgonine (BE), the primary metabolite of cocaine. This will be cross-checked against participants' self-reports of cocaine use through Time-Line Follow Back (TLFB)(Sobell & Sobell, 1992). To compare medication groups' rates of abstinence from drinking, and of clinically significant drinking, as measured by the TLFB. Secondary Exploratory Objectives: To evaluate medication groups' reports of craving for cocaine and alcohol, as measured by scores on the Penn Alcohol Craving Scale and the Minnesota Cocaine Craving Scale during the medication treatment phase. To compare women's reports of medication tolerance of naltrexone extended-release injectable suspension versus high dose oral naltrexone that was reported in our recently published pilot trial of high dose naltrexone for dual cocaine and alcohol dependence (Pettinati et al., 2008).

Official Title
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A Phase II, Randomized, Double-Blind Pilot Trial of VIVITROL® (Naltrexone for Extended-Release Injectable Suspension) for the Treatment of Cocaine and Alcohol Dependence

Conditions
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Cocaine Dependence, Alcohol Dependence

Intervention / Treatment
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* Drug: VIVITROL (Naltrexone extended-release injectable suspension)
* Drug: Placebo


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria Males and females, 18 to 65 years old. Meets DSM-IV criteria for Cocaine Dependence, as determined by the Structured Clinical Interview for DSM-IV (SCID). Meets DSM-IV criteria for Alcohol Dependence, as determined by the Structured Clinical Interview for DSM-IV (SCID). Meets the following drinking criteria as measured by the Timeline Followback (TLFB) (Sobell, 1995) drank within 30 days of intake day, reports a minimum of XX standard alcoholic drinks in a consecutive 30-day period over the 90-day period prior to starting intake, and has 2 or more days of heavy drinking In the past 30 days prior to consent, used no less than $ of cocaine. Live within a commutable distance of the Treatment Research Center (TRC) at the Penn/VA Center for Studies of Addiction, University of Pennsylvania. We define this to be a distance within the service area of Septa, within an hour drive, or a distance that both the patient and Principal Investigator (PI) find acceptable. Understands and signs the informed consent. Three consecutive days of abstinence from alcohol, and a Clinical Institute Withdrawal Scale for Alcohol (CIWA-AR) (Sullivan, 1989) score below eight. 4.2 Exclusion Criteria: Positive urine drug screen and/or current DSM-IV diagnosis of any psychoactive substance dependence other than cocaine, alcohol, or nicotine dependence, as determined by the SCID. Concomitant treatment with psychotropic medications, including opioid analgesics. Patients mandated to treatment based upon a legal decision or as a condition of employment. Current severe psychiatric symptoms, e.g., psychosis, dementia, suicidal or homicidal ideation, mania or depression requiring antidepressant therapy in the opinion of the Principal Investigator (PI). Taken any investigational medication within the past 30 days. History within the six months prior to randomization of significant heart disease (an arrhythmia which required medication, Wolff-Parkinson-White Syndrome, angina pectoris, documented history of myocardial infarction, heart failure). These are to be reviewed on a case-by-case basis: EKG 1st degree heart block, sinus tachycardia, left axis deviation, and nonspecific ST or T wave changes are allowed; liver function tests [LFTs] <3 x ULN are acceptable). Known hypersensitivity to naltrexone, PLG, carboxymethylcellulose, or any other components of the diluent. Subjects with a BMI of 40 and above, as determined by the Body Mass Index Table, or that have distribution of adipose tissue such that they would be at greater risk of serious injection site reaction, based on clinical judgment. Participants with a BMI over 30 will have additional screening procedures conducted to determine inclusion in the study. These procedures include an additional screening measurement of waist-hip ratio for those participants with a BMI over 30. Males with a waist to hip ratio of >0.9 and females with a waist to hip ratio of >0.85 will be referred to the investigator for final decision of study inclusion. If the ratio is <0.9 for men or <0.85 for women they will be eligible for study inclusion without further action. Patients with any serious illnesses that may require hospitalization during the study. Female subjects who are pregnant or lactating, or female subjects of child-bearing potential who are not using acceptable methods of birth control. Acceptable methods of birth control include: Clinical laboratory tests (CBC, blood chemistries, urinalysis) outside normal limits that are clinically unacceptable to the Principal Investigator. Current physiological opioid dependence. Experiencing acute opiate withdrawal. Likely to receive scheduled surgery, which may require treatment with opioid analgesics.

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: 1<br>VIVITROL (Naltrexone extended-release injectable suspension), 380 mg injection at the start of weeks 2 and 6 | Drug: VIVITROL (Naltrexone extended-release injectable suspension)<br>* VIVITROL (Naltrexone extended-release injectable suspension), 380 mg injection at the start of weeks 2 and 6.<br>* Other names: Vivitrol;|
| Placebo Comparator: 2<br>Placebo injection, 380 mg injection at the start of weeks 2 and 6. | Drug: Placebo<br>* Placebo injection at the start of weeks 2 and 6.<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Urine Assay for Benzoylecgonine (BE), the Primary Metabolite of Cocaine. | Percentage of subjects with no cocaine use for at least 3 weeks | 8 week medication phase | 
| Time Line Follow Back -Reported Days of Abstinence From Drinking | Percentage of participants who were abstinent from drinking | 8 week medication phase | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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alcohol, cocaine, addiction, alcoholism, substance dependence, substance abuse