ALK21-018: Effects of Medisorb® Naltrexone (VIVITROL®) on Alcohol Craving in Treatment-seeking, Alcohol-dependent Adults

Study Overview
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Brief Summary
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This was a study of the effects of VIVITROL® on alcohol cue-induced craving and the associated brain activation patterns in alcohol-dependent adults who had recently completed alcohol detoxification and were seeking further treatment for their alcohol dependence. The study was powered to to detect whether VIVITROL attenuates or blocks the BOLD signal increases in response to alcohol-related cues. In the double-blind portion, subjects received a single administration of study drug (VIVITROL 380 mg or placebo). Subjects who completed the double-blind portion could opt to continue to the open-label portion and receive 2 additional months of treatment with VIVITROL 380 mg.

Detailed Description
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The double-blind phase consisted of 6 visits over a 5- to 6-week period and included 2 telephone contacts and 2 functional magnetic resonance imaging (fMRI) scans. The optional open-label extension included 2 visits approximately 1 month apart. Subjects who completed both phases participated in a total of 8 scheduled visits (including 2 fMRI scans and 2 telephone contacts) over a period of up to 14 weeks. At screening, eligible, consenting subjects were given an Actiwatch®-Score device. They were instructed to record their alcohol craving using this device throughout the double-blind phase. The Actiwatch was programmed to beep every 3 hours ±20 minutes, thereby signaling the subjects to enter their craving or desire to use alcohol, at that exact moment, on a scale of 0 to 10 (with 0 being no craving at all and 10 being extreme craving). In addition, subjects entered any drug and/or alcohol use at the time of occurrence. The Actiwatch was not utilized in the open-label portion of the study.

Official Title
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The Effects of VIVITROL® on Alcohol-Related Cue-Induced Craving and BOLD [Blood Oxygen-level-dependent] Functional Magnetic Resolution Imaging (fMRI) Signal Activation Patterns

Conditions
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Alcohol Dependence

Intervention / Treatment
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* Drug: VIVITROL 380 mg
* Drug: Placebo


Participation Criteria
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Eligibility Criteria
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Primary Inclusion Criteria: Current diagnosis of alcohol dependence, meeting at least 3 criteria from the Diagnostic and Statistical Manual of Mental Disorders, 4th Ed. (DSM-IV) Recently completed alcohol detoxification and seeking treatment for alcohol dependence Women of childbearing potential must agree to use an approved method of contraception for study duration Primary Exclusion Criteria: Pregnancy or lactation Evidence of hepatic failure including: ascites, bilirubin >10% above upper limit of normal (ULN) and/or esophageal variceal disease Current dependence (within the past year) to benzodiazepines or cocaine, or current or history of opioid dependence according to DSM-IV criteria Use of any opioids and/or methadone within 14 days prior to the screening visit, or likely to require opioid therapy during the study period Previous enrollment in a VIVITROL clinical trial or previous VIVITROL experience Known intolerance and/or hypersensitivity to naltrexone, carboxymethylcellulose, or polylactide-co-glycolide (PLG) Parole, probation, or pending legal proceedings having the potential for incarceration during the study period

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: Quadruple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: VIVITROL 380 mg<br> | Drug: VIVITROL 380 mg<br>* Administered via intramuscular (IM) injection once during the double-blind phase and for 2 additional injections, 4 weeks apart, during the optional open-label extension.<br>* Other names: Medisorb® naltrexone;|
| Placebo Comparator: Placebo<br> | Drug: Placebo<br>* Placebo matching VIVITROL 380 mg was administered by IM injection once during the double-blind phase, only.<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Change From Baseline in Blood Oxygen-level-dependent (BOLD) Signal Activation Values Detected in the Reward Circuitry of the Brain in Alcohol-dependent Subjects After Presentation of Alcohol-related Cues. | As was standard among fMRI studies conducted at the study site at the time, a change in BOLD signal in the range of 5% to 6% in anterior cingulate as measured using a 3T magnet,is considered highly significant in block-designed experiments. | 14 days (Baseline to Day 14) | 
| Change From Baseline in BOLD Signal Activation Values for the Inferior Frontal Gyrus |  | 14 days (Baseline to Day 14) | 
| Change From Baseline in BOLD Signal Activation Values in the Reward Circuitry |  | 14 days (Baseline to Day 14) | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Change From Baseline in Obsessive-Compulsive Drinking Scale (OCDS) Score in Alcohol-dependent Subjects | There are 14 items on the Obsessive Compulsive Drinking Scale (OCDS). The scale is scored from 0 to 40 (units). A score of 0 units indicates no obsession-compulsion with respect to alcohol (best score). A score of 40 units indicates maximum obsession-compulsion with respect to alcohol (worst score). A negative Change from Baseline value indicates an improvement. For scoring methods, see: Anton RF, Moak DH, Latham P (1995), The Obsessive Compulsive Drinking Scale: A self-rated instrument for the quantification of thoughts about alcohol and drinking behavior. Alcohol Clin Exp Res 19:92-9. | 28 days (Baseline to Day 28) | 
| Change From Baseline in Daily Craving Score in Alcohol-dependent Subjects (Actiwatch Data) | The Actiwatch-Score device (MiniMitter Co.) was used to collect data on daily alcohol craving. The Actiwatch device is a wrist-worn, battery-operated monitor programmed to beep every 3 hours ±20 minutes, to signal the subjects to enter their alcohol craving or desire to use alcohol at that exact moment on a scale of 0 to 10 units: 0 indicates no craving at all (best score) and 10 indicates extreme craving (worst score). A negative result for Change in Baseline at Day 28 indicates an improvement in daily craving as of 1 month after study drug administration. | 28 days (Baseline to Day 28) | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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alcoholism, addiction, alcohol detoxification