Study of the Effectiveness of Quetiapine for the Treatment of Alcohol Dependency

Study Overview
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Brief Summary
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The purpose of this study is to determine whether quetiapine fumarate extended release is effective in the treatment of alcohol dependence in very heavy drinkers.

Detailed Description
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This study will investigate quetiapine fumarate XR (SEROQUEL XR®), a dibenzothiazepine derivative, as a potential medication for treating alcohol dependence. The immediate release form of quetiapine fumarate, SEROQUEL XR®, is approved by the FDA for treatment of schizophrenia and acute manic episodes associated with bipolar disorder. The extended release formulation (SEROQUEL XR®) is also approved by the FDA and is undergoing clinical investigation for the treatment of major depressive disorders, schizophrenia, generalized anxiety disorder, and alcohol dependence. Treatment with other atypical antipsychotics such as clozapine and olanzapine has resulted in decreases in alcohol use in alcohol dependent patients with and without comorbid psychiatric diagnoses. Quetiapine, like clozapine, appears to have efficacy in reducing drug and alcohol use among alcoholics and drug dependent patients with co-morbid psychiatric illness.

Official Title
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A Phase 2, Double-Blind, Placebo Controlled Trial to Assess the Efficacy of Quetiapine Fumarate Extended Release for the Treatment of Alcohol Dependence in Very Heavy Drinkers.

Conditions
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Alcoholism, Alcohol Abuse

Intervention / Treatment
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* Drug: Quetiapine fumarate
* Other: Placebo


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Between the ages of 18 and 65 years old DSM-IV diagnosis of current alcohol dependence as supported by SCID Module E Report very heavy drinking (10 or more drinks per drinking day for men or 8 or more drinks per drinking day for women) at least 40% of the days during the interval from day 31 to 90 prior to the initial screening visit (i.e. a total of 24 days of this 60-day period), with at least one day of very heavy drinking occurring within the last 2 weeks before screening Seeking treatment for alcohol dependence and desire reduction or cessation of drinking Able to verbalize understanding of the consent form, able to provide written informed consent, and verbalize willingness to complete study procedures Females of child bearing potential must agree to use of at least one approved method of birth control, or must be surgically sterile or postmenopausal Able to take oral medication, willing to adhere to the medication regimen, and willing to return for regular visits Able to understand written and oral instructions in English and to complete the questionnaires required by the protocol Can complete all psychological assessments required at screening and baseline Able to provide evidence of stable residence in the last 2 months prior to randomization, have reasonable transportation arrangements to study site, and have no plans to move within the next 3 months or unresolved legal problems; must provide contact information of family member, spouse, or significant other who can contact subject in case of missed appointment Breath alcohol concentration (BAC) equal to 0.00 when s/he signed the informed consent document Must have an absolute neutrophil count of 1.5 x 109/L or greater. Exclusion Criteria: Please contact site for additional information.

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>Quetiapine fumarate plus medical management | Drug: Quetiapine fumarate<br>* Quetiapine fumarate- taken daily, for 12 weeks<br>* Other names: SEROQUEL XR;|
| Placebo Comparator: 2<br>Medical management plus placebo comparator | Other: Placebo<br>* Placebo<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Percent Heavy Drinking Days | A heavy drinking day is defined as 5 or more drinks for men and 4 or more drinks for women during a 24 hour period. | Weeks 3 - 11 | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Percent Days Abstinent | Timeline Follow-back drinking data is used to calculate the % of days abstinent per week during Weeks 3-11 | Weeks 3-11 | 
| Drinks Per Drinking Day | Timeline Follow Back daily drinking data used to calculate the weekly mean drinks per drinking day | Study Weeks 3-11 | 
| Drinks Per Day | Timeline Follow Back daily drinking data used to calculate the weekly mean drinks per day | Study Weeks 3-11 | 
| Percent Very Heavy Drinking Day | Timeline Follow Back data used to calculate the % of very heavy drinking days per week. Heavy drinking is 10+ drinks per day for females and 12+ drinks per day for males | Study Weeks 3-11 | 
| Percent Subjects Abstinent | Timeline Follow Back data used to calculate the % of subjects that maintained abstinence weeks 3-11. | Study Weeks 3-11 | 
| Percent Subjects With no Heavy Drinking Day | Timeline Follow Back data used to calculate the % of subjects that didn't have a heavy drinking day during study weeks 3-11. | Study Weeks 3-11 | 
| Drinking Consequences Score | Drinkers Inventory of Consequences (DrInC) - Alcohol-related problems are determined using the DrInC (Miller et al., 1995). The DrInC is a self-administered 50-item questionnaire designed to measure adverse consequences of alcohol abuse in five areas: Interpersonal, Physical, Social, Impulsive, and Intrapersonal. Each scale provides a lifetime and past 3-month measure of adverse consequences, and scales can be combined to assess total adverse consequences. We used a modified version of the DrInC that just included the 45-items that summed the Interpersonal, Physical, Social, and Impulsivity items. This total score (min=0, max=135) was analyzed in this study with high scores indicative of more alcohol-related consequences (a poor outcome for a given study participant). The DrInC was assessed at study weeks 6 and 12. Analyses averaged across these weeks. | Weeks 6 & 12 | 
| Penn Alcohol Craving Score (PACS_ | The Penn Alcohol Craving Scale (PACS) is a five-item, self-report measure that includes questions about the frequency, intensity, and duration of craving, the ability to resist drinking, and asks for an overall rating of craving for alcohol for the previous week (Flannery et al., 1999). The summed total score of the 5 items was used in the analysis (min=0, max=30) with higher scores indicative of higher craving for alcohol (a poor outcome). Based on clinical study results, the PACS has been shown to be a reliable and valid measure of alcohol craving and can predict subjects at risk for subsequent relapse. The PACS was assessed at study weeks 4, 6, 8, 10, and 12. Analyses averaged across these weeks. | Weeks 4, 6, 8, 10, and 12 | 
| Montgomery-Asberg Depression Rating Scale (MADRS) | The MADRS is an observer rating scale that has proven to be an efficient and practical measure of depression (Montgomery and Asberg, 1979). The scale was constructed to be sensitive to changes in treatment effects. Its capacity to differentiate between responders and non-responders to antidepressant treatment has been shown to be comparable to the Hamilton Rating Scale for Depression, another established measure of depressive symptomatology, but the MADRS has greater sensitivity to change during the course of a depressive phase. It has exhibited high inter-rater reliability and appears to be oriented more towards psychic as opposed to somatic aspects of depression. The MADRS is the sum of the 10-item in a checklist where items are rated on a scale of 0 to 6 with anchors at 2-point intervals. Scores range from 0 to 60. Higher scores are indicative of greater depressive symptoms (a poor outcome). The MADRS was assessed at weeks 4, 6, 8, 10, and 12. Analyses averaged across these weeks. | Weeks 3-11 | 
| Hamilton Anxiety Scale (HAM-A) | The Hamilton Anxiety Scale consists of 14 items, each defined by a series of symptoms. Similar to the HAM-D, each item is rated on a 5-point scale, ranging from 0 (not present) to 4 (severe) (Guy, 1976). A total score is derived from the summed items (min=0, max=56) with higher scores indicative of greater anxiety (a poor outcome). The HAM-A was assessed at study weeks 4, 6, 8, 10, and 12. Analyses averaged across these weeks. | Weeks 4, 6, 8, 10, and 12 | 
| Pittsburgh Sleep Quality Score | The PSQI is a 19-item questionnaire assessing the subject's overall sleep experience in the past 30 days (Buysse et al-1989). The lower the overall score, the better the person sleeps. The tool has an adequate internal reliability, validity and consistency for clinical and community samples of the various populations. Range is (0-21); >6 indicative of poor sleep quality. The PSQI was assessed at study weeks 4,8, and 12. Analyses averaged across these weeks. | Weeks 4, 8, 12 | 
| Quality of Life SF - 12 - Mental Aggregate Score | The SF-12 will be used to assess overall health status. The SF-12 is a 12-item questionnaire developed in 1994 as a shorter alternative to the SF-36 to reproduce the physical and mental health summary measures with at least 90% accuracy. We calculated the physical and mental component summary scores which were both converted to T-scores (min=0, max=100) normed to the general population such that a T=50 is the average score in the general population. Higher scores are indicative of better health status. | Week 12 | 
| Quality of Life SF-12 - Physical Aggregate Score | The SF-12 will be used to assess overall health status. The SF-12 is a 12-item questionnaire developed in 1994 as a shorter alternative to the SF-36 to reproduce the physical and mental health summary measures with at least 90% accuracy. We calculated the physical and mental component summary scores which were both converted to T-scores (min=0, max=100) normed to the general population such that a T=50 is the average score in the general population. Higher scores are indicative of better health status. | Week 12 | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Alcoholism, Alcohol dependence, Quetiapine