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

Primary Purpose

Alcoholism, Alcohol Abuse

Status
Completed
Phase
Phase 2
Locations
United States
Study Type
Interventional
Intervention
Quetiapine fumarate
Placebo
Sponsored by
National Institute on Alcohol Abuse and Alcoholism (NIAAA)
About
Eligibility
Locations
Arms
Outcomes
Full info

About this trial

This is an interventional treatment trial for Alcoholism focused on measuring Alcoholism, Alcohol dependence, Quetiapine

Eligibility Criteria

18 Years - 65 Years (Adult, Older Adult)All SexesDoes not accept healthy volunteers

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.

Sites / Locations

  • Boston University School of Medicine, Psychiatry Clinical Studies Unit
  • Dartmouth Medical School, Dept. of Psychiatry
  • University of Pennsylvania, Treatment Research Center
  • Brown University Center for Alcohol and Addiction Studies
  • White River Junction VA Medical Center
  • University of Virginia, Dept. of Psychiatric Medicine
  • University of Virginia

Arms of the Study

Arm 1

Arm 2

Arm Type

Experimental

Placebo Comparator

Arm Label

1

2

Arm Description

Quetiapine fumarate plus medical management

Medical management plus placebo comparator

Outcomes

Primary Outcome Measures

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.

Secondary Outcome Measures

Percent Days Abstinent
Timeline Follow-back drinking data is used to calculate the % of days abstinent per week during Weeks 3-11
Drinks Per Drinking Day
Timeline Follow Back daily drinking data used to calculate the weekly mean drinks per drinking day
Drinks Per Day
Timeline Follow Back daily drinking data used to calculate the weekly mean drinks per day
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
Percent Subjects Abstinent
Timeline Follow Back data used to calculate the % of subjects that maintained abstinence 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.
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.
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.
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.
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.
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.
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.
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.

Full Information

First Posted
July 6, 2007
Last Updated
February 26, 2019
Sponsor
National Institute on Alcohol Abuse and Alcoholism (NIAAA)
Collaborators
National Institute on Drug Abuse (NIDA), AstraZeneca, US Department of Veterans Affairs
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1. Study Identification

Unique Protocol Identification Number
NCT00498628
Brief Title
Study of the Effectiveness of Quetiapine for the Treatment of Alcohol Dependency
Official Title
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.
Study Type
Interventional

2. Study Status

Record Verification Date
February 2019
Overall Recruitment Status
Completed
Study Start Date
December 2007 (undefined)
Primary Completion Date
August 2009 (Actual)
Study Completion Date
March 2010 (Actual)

3. Sponsor/Collaborators

Responsible Party, by Official Title
Sponsor
Name of the Sponsor
National Institute on Alcohol Abuse and Alcoholism (NIAAA)
Collaborators
National Institute on Drug Abuse (NIDA), AstraZeneca, US Department of Veterans Affairs

4. Oversight

Data Monitoring Committee
Yes

5. Study Description

Brief Summary
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
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.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Alcoholism, Alcohol Abuse
Keywords
Alcoholism, Alcohol dependence, Quetiapine

7. Study Design

Primary Purpose
Treatment
Study Phase
Phase 2
Interventional Study Model
Parallel Assignment
Masking
ParticipantCare ProviderInvestigator
Allocation
Randomized
Enrollment
224 (Actual)

8. Arms, Groups, and Interventions

Arm Title
1
Arm Type
Experimental
Arm Description
Quetiapine fumarate plus medical management
Arm Title
2
Arm Type
Placebo Comparator
Arm Description
Medical management plus placebo comparator
Intervention Type
Drug
Intervention Name(s)
Quetiapine fumarate
Other Intervention Name(s)
SEROQUEL XR
Intervention Description
Quetiapine fumarate- taken daily, for 12 weeks
Intervention Type
Other
Intervention Name(s)
Placebo
Intervention Description
Placebo
Primary Outcome Measure Information:
Title
Percent Heavy Drinking Days
Description
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.
Time Frame
Weeks 3 - 11
Secondary Outcome Measure Information:
Title
Percent Days Abstinent
Description
Timeline Follow-back drinking data is used to calculate the % of days abstinent per week during Weeks 3-11
Time Frame
Weeks 3-11
Title
Drinks Per Drinking Day
Description
Timeline Follow Back daily drinking data used to calculate the weekly mean drinks per drinking day
Time Frame
Study Weeks 3-11
Title
Drinks Per Day
Description
Timeline Follow Back daily drinking data used to calculate the weekly mean drinks per day
Time Frame
Study Weeks 3-11
Title
Percent Very Heavy Drinking Day
Description
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
Time Frame
Study Weeks 3-11
Title
Percent Subjects Abstinent
Description
Timeline Follow Back data used to calculate the % of subjects that maintained abstinence weeks 3-11.
Time Frame
Study Weeks 3-11
Title
Percent Subjects With no Heavy Drinking Day
Description
Timeline Follow Back data used to calculate the % of subjects that didn't have a heavy drinking day during study weeks 3-11.
Time Frame
Study Weeks 3-11
Title
Drinking Consequences Score
Description
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.
Time Frame
Weeks 6 & 12
Title
Penn Alcohol Craving Score (PACS_
Description
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.
Time Frame
Weeks 4, 6, 8, 10, and 12
Title
Montgomery-Asberg Depression Rating Scale (MADRS)
Description
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.
Time Frame
Weeks 3-11
Title
Hamilton Anxiety Scale (HAM-A)
Description
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.
Time Frame
Weeks 4, 6, 8, 10, and 12
Title
Pittsburgh Sleep Quality Score
Description
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.
Time Frame
Weeks 4, 8, 12
Title
Quality of Life SF - 12 - Mental Aggregate Score
Description
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.
Time Frame
Week 12
Title
Quality of Life SF-12 - Physical Aggregate Score
Description
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.
Time Frame
Week 12

10. Eligibility

Sex
All
Minimum Age & Unit of Time
18 Years
Maximum Age & Unit of Time
65 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
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.
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Raye Z. Litten, PhD
Organizational Affiliation
National Institute on Alcohol Abuse and Alcoholism (NIAAA)
Official's Role
Study Director
First Name & Middle Initial & Last Name & Degree
Margaret E. Mattson, PhD
Organizational Affiliation
National Institute on Alcohol Abuse and Alcoholism (NIAAA)
Official's Role
Principal Investigator
First Name & Middle Initial & Last Name & Degree
Joanne Fertig, PhD
Organizational Affiliation
National Institute on Alcohol Abuse and Alcoholism (NIAAA)
Official's Role
Principal Investigator
Facility Information:
Facility Name
Boston University School of Medicine, Psychiatry Clinical Studies Unit
City
Boston
State/Province
Massachusetts
ZIP/Postal Code
02118
Country
United States
Facility Name
Dartmouth Medical School, Dept. of Psychiatry
City
Lebanon
State/Province
New Hampshire
ZIP/Postal Code
03755
Country
United States
Facility Name
University of Pennsylvania, Treatment Research Center
City
Philadelphia
State/Province
Pennsylvania
ZIP/Postal Code
19104
Country
United States
Facility Name
Brown University Center for Alcohol and Addiction Studies
City
Providence
State/Province
Rhode Island
ZIP/Postal Code
12906
Country
United States
Facility Name
White River Junction VA Medical Center
City
White River Junction
State/Province
Vermont
ZIP/Postal Code
05009
Country
United States
Facility Name
University of Virginia, Dept. of Psychiatric Medicine
City
Charlottesville
State/Province
Virginia
ZIP/Postal Code
22908
Country
United States
Facility Name
University of Virginia
City
Richmond
State/Province
Virginia
ZIP/Postal Code
23294
Country
United States

12. IPD Sharing Statement

Citations:
PubMed Identifier
21950727
Citation
Litten RZ, Fertig JB, Falk DE, Ryan ML, Mattson ME, Collins JF, Murtaugh C, Ciraulo D, Green AI, Johnson B, Pettinati H, Swift R, Afshar M, Brunette MF, Tiouririne NA, Kampman K, Stout R; NCIG 001 Study Group. A double-blind, placebo-controlled trial to assess the efficacy of quetiapine fumarate XR in very heavy-drinking alcohol-dependent patients. Alcohol Clin Exp Res. 2012 Mar;36(3):406-16. doi: 10.1111/j.1530-0277.2011.01649.x. Epub 2011 Sep 26.
Results Reference
result
PubMed Identifier
32963470
Citation
Vatsalya V, Kong M, Marsano LM, Kurlawala Z, Chandras KV, Schwandt ML, Ramchandani VA, McClain CJ. Interaction of Heavy Drinking Patterns and Depression Severity Predicts Efficacy of Quetiapine Fumarate XR in Lowering Alcohol Intake in Alcohol Use Disorder Patients. Subst Abuse. 2020 Sep 9;14:1178221820955185. doi: 10.1177/1178221820955185. eCollection 2020.
Results Reference
derived

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

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