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Zonisamide vs. Placebo in the Treatment of Alcohol Dependence

This study has been completed.
Sponsor:
Collaborators:
Information provided by:
University of Connecticut Health Center
ClinicalTrials.gov Identifier:
NCT00595556
First received: January 6, 2008
Last updated: September 28, 2010
Last verified: September 2010
Results First Received: May 15, 2010  
Study Type: Interventional
Study Design: Allocation: Randomized;   Endpoint Classification: Efficacy Study;   Intervention Model: Parallel Assignment;   Masking: Double Blind (Subject, Caregiver, Investigator);   Primary Purpose: Treatment
Conditions: Alcoholism
Alcohol Abuse
Alcohol Dependence
Interventions: Drug: zonisamide
Drug: Placebo

  Participant Flow
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Recruitment Details
Key information relevant to the recruitment process for the overall study, such as dates of the recruitment period and locations
No text entered.

Pre-Assignment Details
Significant events and approaches for the overall study following participant enrollment, but prior to group assignment
No text entered.

Reporting Groups
  Description
Zonisamide Medication Treatment Subjects in this arm received the zonisamide anticonvulsant medication in double blind fashion starting with 100mg daily and titrated every other week to a target dose of 500mg daily. The pills were over-encapsulated to match the placebo.
Placebo Subjects in this arm received a double blind placebo lactose capsule identical to the over-capsule on the actual medicine. The titration of "dose" and number of pills matched that of the zonisamide arm.

Participant Flow:   Overall Study
    Zonisamide Medication Treatment     Placebo  
STARTED     20     20  
COMPLETED     17     19  
NOT COMPLETED     3     1  



  Baseline Characteristics
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Population Description
Explanation of how the number of participants for analysis was determined. Includes whether analysis was per protocol, intention to treat, or another method. Also provides relevant details such as imputation technique, as appropriate.
No text entered.

Reporting Groups
  Description
Zonisamide Medication Treatment Subjects in this arm received the zonisamide anticonvulsant medication in double blind fashion starting with 100mg daily and titrated every other week to a target dose of 500mg daily. The pills were over-encapsulated to match the placebo.
Placebo Subjects in this arm received a double blind placebo lactose capsule identical to the over-capsule on the actual medicine. The titration of "dose" and number of pills matched that of the zonisamide arm.
Total Total of all reporting groups

Baseline Measures
    Zonisamide Medication Treatment     Placebo     Total  
Number of Participants  
[units: participants]
  20     20     40  
Age  
[units: participants]
     
<=18 years     0     0     0  
Between 18 and 65 years     20     20     40  
>=65 years     0     0     0  
Age  
[units: years]
Mean ± Standard Deviation
  47.8  ± 9.9     50.4  ± 11     49.1  ± 10  
Gender  
[units: participants]
     
Female     8     9     17  
Male     12     11     23  
Region of Enrollment  
[units: participants]
     
United States     20     20     40  



  Outcome Measures
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1.  Primary:   Change in Number of Heavy Drinking Days (i.e., 5 or More Drinks Per Day for Men, and 4 or More Per Day for Women)Per Week, by Week   [ Time Frame: baseline to the end of 12 weeks in treatment ]

Measure Type Primary
Measure Title Change in Number of Heavy Drinking Days (i.e., 5 or More Drinks Per Day for Men, and 4 or More Per Day for Women)Per Week, by Week
Measure Description This outcome measure represents the change in number of heavy drinking days (i.e., 5 or more drinks per day for men, and 4 or more per day for women)per week, from baseline to the end of week twelve. This was analyzed using weekly measurements over the 12 week study period (thirteen time points, 12 measurements)with a repeated measures analysis (SPSS linear mixed models), by interaction with time (week).
Time Frame baseline to the end of 12 weeks in treatment  
Safety Issue No  

Population Description
Explanation of how the number of participants for analysis was determined. Includes whether analysis was per protocol, intention to treat, or another method. Also provides relevant details such as imputation technique, as appropriate.
No text entered.

Reporting Groups
  Description
Zonisamide Medication Treatment Subjects in this arm received the zonisamide anticonvulsant medication in double blind fashion starting with 100mg daily and titrated every other week to a target dose of 500mg daily. The pills were over-encapsulated to match the placebo.
Placebo Subjects in this arm received a double blind placebo lactose capsule identical to the over-capsule on the actual medicine. The titration of "dose" and number of pills matched that of the zonisamide arm.

Measured Values
    Zonisamide Medication Treatment     Placebo  
Number of Participants Analyzed  
[units: participants]
  20     20  
Change in Number of Heavy Drinking Days (i.e., 5 or More Drinks Per Day for Men, and 4 or More Per Day for Women)Per Week, by Week  
[units: Days/week]
Mean ± Standard Deviation
  -.30  ± .362     -.20  ± .362  


Statistical Analysis 1 for Change in Number of Heavy Drinking Days (i.e., 5 or More Drinks Per Day for Men, and 4 or More Per Day for Women)Per Week, by Week
Groups [1] All groups
Method [2] Mixed Models Analysis
P Value [3] .012
[1] Additional details about the analysis, such as null hypothesis and power calculation:
  No text entered.
[2] Other relevant method information, such as adjustments or degrees of freedom:
  No text entered.
[3] Additional information, such as whether or not the p-value is adjusted for multiple comparisons and the a priori threshold for statistical significance:
  No text entered.



2.  Primary:   Weekly Rate of Change in Abstinent Days   [ Time Frame: baseline to the end of 12 weeks in treatment ]

Measure Type Primary
Measure Title Weekly Rate of Change in Abstinent Days
Measure Description This outcome measure analyzed the weekly rate of change in number of abstinent days over the twelve weeks of the study from baseline to the end of week twelve. This was analyzed using weekly measurements over the 12 week study period (thirteen time points, 12 measurements)with a repeated measures analysis (SPSS proc mixed), by interaction with time (week).
Time Frame baseline to the end of 12 weeks in treatment  
Safety Issue No  

Population Description
Explanation of how the number of participants for analysis was determined. Includes whether analysis was per protocol, intention to treat, or another method. Also provides relevant details such as imputation technique, as appropriate.
No text entered.

Reporting Groups
  Description
Zonisamide Medication Treatment Subjects in this arm received the zonisamide anticonvulsant medication in double blind fashion starting with 100mg daily and titrated every other week to a target dose of 500mg daily. The pills were over-encapsulated to match the placebo.
Placebo Subjects in this arm received a double blind placebo lactose capsule identical to the over-capsule on the actual medicine. The titration of "dose" and number of pills matched that of the zonisamide arm.

Measured Values
    Zonisamide Medication Treatment     Placebo  
Number of Participants Analyzed  
[units: participants]
  20     20  
Weekly Rate of Change in Abstinent Days  
[units: days/week]
Mean ± Standard Error
  0.17  ± .02     0.13  ± .02  


Statistical Analysis 1 for Weekly Rate of Change in Abstinent Days
Groups [1] All groups
Method [2] Mixed Models Analysis
P Value [3] .94
[1] Additional details about the analysis, such as null hypothesis and power calculation:
  No text entered.
[2] Other relevant method information, such as adjustments or degrees of freedom:
  No text entered.
[3] Additional information, such as whether or not the p-value is adjusted for multiple comparisons and the a priori threshold for statistical significance:
  No text entered.



3.  Secondary:   Change in Number of Drinks Per Week by Week   [ Time Frame: baseline to the end of 12 weeks in treatment ]

Measure Type Secondary
Measure Title Change in Number of Drinks Per Week by Week
Measure Description This outcome measure represents the change in the total number of standard drinks per week (weekly data) from baseline to the end of week twelve. This was analyzed using weekly measurements from baseline to week 12 week of the study period (thirteen time points, 12 measurements)with a repeated measures analysis (SPSS linear mixed models), by interaction with time (week).
Time Frame baseline to the end of 12 weeks in treatment  
Safety Issue No  

Population Description
Explanation of how the number of participants for analysis was determined. Includes whether analysis was per protocol, intention to treat, or another method. Also provides relevant details such as imputation technique, as appropriate.
The analysis was intention to treat and last observation carried forward

Reporting Groups
  Description
Zonisamide Medication Treatment Subjects in this arm received the zonisamide anticonvulsant medication in double blind fashion starting with 100mg daily and titrated every other week to a target dose of 500mg daily. The pills were over-encapsulated to match the placebo.
Placebo Subjects in this arm received a double blind placebo lactose capsule identical to the over-capsule on the actual medicine. The titration of "dose" and number of pills matched that of the zonisamide arm.

Measured Values
    Zonisamide Medication Treatment     Placebo  
Number of Participants Analyzed  
[units: participants]
  20     20  
Change in Number of Drinks Per Week by Week  
[units: drinks/week]
Mean ± Standard Deviation
  -2.2  ± 20.5     -1.4  ± 20.5  


Statistical Analysis 1 for Change in Number of Drinks Per Week by Week
Groups [1] All groups
Method [2] Mixed Models Analysis
P Value [3] .004
[1] Additional details about the analysis, such as null hypothesis and power calculation:
  No text entered.
[2] Other relevant method information, such as adjustments or degrees of freedom:
  No text entered.
[3] Additional information, such as whether or not the p-value is adjusted for multiple comparisons and the a priori threshold for statistical significance:
  No text entered.



4.  Secondary:   Change in the Urge to Drink Alcohol as Measured by the Alcohol Urge Questionnaire (AUQ)   [ Time Frame: baseline to the end of 12 weeks in treatment ]

Measure Type Secondary
Measure Title Change in the Urge to Drink Alcohol as Measured by the Alcohol Urge Questionnaire (AUQ)
Measure Description This is the change in measured urge to drink alcohol as measured by the Alcohol Urge Questionnaire (AUQ), measured every 2 weeks from baseline until the last week of the study (over twelve weeks, 7 timepoint measurements of AUQ, 6 calculated changes). It is reported in terms of change per visit (every 2 weeks). AUQ measures a feeling state, and uses a 7 point (1-7)Likert scale for each of 8 items (questions). The lowest urge score is 8 (representing less urge to drink), and the highest would be tabulated as 56 (meaning more urge to drink). Repeated measures SPPS linear mixed models used.
Time Frame baseline to the end of 12 weeks in treatment  
Safety Issue No  

Population Description
Explanation of how the number of participants for analysis was determined. Includes whether analysis was per protocol, intention to treat, or another method. Also provides relevant details such as imputation technique, as appropriate.
No text entered.

Reporting Groups
  Description
Zonisamide Medication Treatment Subjects in this arm received the zonisamide anticonvulsant medication in double blind fashion starting with 100mg daily and titrated every other week to a target dose of 500mg daily. The pills were over-encapsulated to match the placebo.
Placebo Subjects in this arm received a double blind placebo lactose capsule identical to the over-capsule on the actual medicine. The titration of "dose" and number of pills matched that of the zonisamide arm.

Measured Values
    Zonisamide Medication Treatment     Placebo  
Number of Participants Analyzed  
[units: participants]
  20     20  
Change in the Urge to Drink Alcohol as Measured by the Alcohol Urge Questionnaire (AUQ)  
[units: units on a scale/visit]
Mean ± Standard Deviation
  -1.4  ± 1     -0.6  ± 1  


Statistical Analysis 1 for Change in the Urge to Drink Alcohol as Measured by the Alcohol Urge Questionnaire (AUQ)
Groups [1] All groups
Method [2] Mixed Models Analysis
P Value [3] .006
[1] Additional details about the analysis, such as null hypothesis and power calculation:
  No text entered.
[2] Other relevant method information, such as adjustments or degrees of freedom:
  No text entered.
[3] Additional information, such as whether or not the p-value is adjusted for multiple comparisons and the a priori threshold for statistical significance:
  No text entered.



5.  Secondary:   Change in Gamma-glutamyl Transferase (GGT) Concentration   [ Time Frame: 12 weeks (from initiation to end of treatment) ]

Measure Type Secondary
Measure Title Change in Gamma-glutamyl Transferase (GGT) Concentration
Measure Description This outcome measure looks at the change in blood levels of this enzyme assay from baseline, and then after 6 weeks (midpoint), and then at the endpoint (12 weeks). The analysis takes into account all three time points, and reports the average change between each of the three time points.
Time Frame 12 weeks (from initiation to end of treatment)  
Safety Issue No  

Population Description
Explanation of how the number of participants for analysis was determined. Includes whether analysis was per protocol, intention to treat, or another method. Also provides relevant details such as imputation technique, as appropriate.
No text entered.

Reporting Groups
  Description
Zonisamide Medication Treatment Subjects in this arm received the zonisamide anticonvulsant medication in double blind fashion starting with 100mg daily and titrated every other week to a target dose of 500mg daily. The pills were over-encapsulated to match the placebo.
Placebo Subjects in this arm received a double blind placebo lactose capsule identical to the over-capsule on the actual medicine. The titration of "dose" and number of pills matched that of the zonisamide arm.

Measured Values
    Zonisamide Medication Treatment     Placebo  
Number of Participants Analyzed  
[units: participants]
  20     20  
Change in Gamma-glutamyl Transferase (GGT) Concentration  
[units: Units/Liter]
Mean ± Standard Deviation
  8.4  ± 36.2     2.9  ± 36.2  


Statistical Analysis 1 for Change in Gamma-glutamyl Transferase (GGT) Concentration
Groups [1] All groups
Method [2] Mixed Models Analysis
P Value [3] .3
[1] Additional details about the analysis, such as null hypothesis and power calculation:
  No text entered.
[2] Other relevant method information, such as adjustments or degrees of freedom:
  No text entered.
[3] Additional information, such as whether or not the p-value is adjusted for multiple comparisons and the a priori threshold for statistical significance:
  No text entered.




  Serious Adverse Events


  Other Adverse Events


  Limitations and Caveats
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Limitations of the study, such as early termination leading to small numbers of participants analyzed and technical problems with measurement leading to unreliable or uninterpretable data
The small sample size and the short duration of treatment are limitations. High rates of retention in the treatment and adherence to the medication regimen are strengths. The concomitant psychotherapy may have caused a ceiling effect on medication.


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