Zonisamide vs. Placebo in the Treatment of Alcohol Dependence

Study Overview
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Brief Summary
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This is a pilot study designed to examine the potential efficacy and tolerability of zonisamide compared to placebo for the treatment of alcohol dependence.

Detailed Description
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Zonisamide is an antiepileptic medication which has similar clinical and pharmacologic effects to topiramate, a medication that has demonstrated efficacy in a randomized clinical trial for treatment of alcoholism. Because zonisamide is potentially better tolerated and easier to titrate in the outpatient setting than topiramate, it may offer important clinical advantages in the treatment of alcoholism. This is a small 12-week placebo-controlled pilot study examining tolerability and potential efficacy in anticipation of a larger, placebo-controlled trial of zonisamide for treatment of alcohol dependence. It is a randomized, double-blind trial of zonisamide vs. placebo at flexible dosages of 100-500mg/day in alcoholics receiving ambulatory psychosocial treatment. Participants will take part in six individual Cognitive-Behavioral based therapy sessions, which are focused on learning coping skills. Participants must endorse a goal of either cutting down their drinking to non-hazardous levels, or abstinence.

Official Title
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Zonisamide vs. Placebo in the Treatment of Alcohol Dependence

Conditions
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Alcoholism, Alcohol Abuse, Alcohol Dependence

Intervention / Treatment
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* Drug: zonisamide
* Drug: Placebo


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: age 18 to 65 years, inclusive current Diagnostic & Statistical Manual of Mental Disorders 4th ed (DSM-IV) alcohol dependence (within the past month) have 2 heavy drinking days per week during the period between screening and baseline (defined as >4 standard drinks per day for males, and >3 standard drinks per day for females) able to read at the eighth grade or higher level and show no evidence of significant cognitive impairment if a woman of child-bearing potential (i.e., who has not had a hysterectomy, bilateral oophorectomy, tubal ligation or who is less than two years postmenopausal), must be non-lactating, practicing a reliable method of birth control including barrier method; and have a negative serum pregnancy test prior to initiation of treatment be willing to provide signed, informed consent to participate in the study Exclusion Criteria: have a current, clinically significant physical disease or abnormality (i.e., neurologic, renal, rheumatologic, gastrointestinal, hematologic, pulmonary, endocrine, cardiovascular, hepatic, or autoimmune disease that, in the context of the study would represent a risk to the subject, or significant laboratory abnormalities such as hepatic aminotransferase levels greater than 300% of the uper limit of normal or direct bilirubin levels 150% of the upper limit of normal) on the basis of medical history, physician examination, or routine laboratory evaluation. Serum creatinine level of > 1.2 mg/dl will also be exclusionary. Other specific exclusionary disorders include: patients with a history of renal calculi patients with a history of hypersensitivity to zonisamide or any sulfonamide, Stevens-Johnson Syndrome, penicillin allergy, or history of any severe drug allergic reaction patients with a significant history of systemic autoimmune disease such as lupus erythematosis, fibromyalgia, or rheumatoid arthritis patients with a current blood dyscrasia or a history of such, with the exception of a remote history of iron deficient anemia have a serious psychiatric illness (i.e., schizophrenia, bipolar disorder, severe or psychotic major depression, panic disorder, or substantial suicide or violence risk) on the basis of history or psychiatric examination current dependence on opioids or benzodiazepines or other sedatives will also be exclusionary are considered by investigators to be clinically inappropriate for study participation because individuals with a history of seizure disorder could potentially be at increased risk of experiencing a seizure due to their drinking, such individuals will also be excluded have participated in another pharmacotherapy study in the past thirty days

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: A<br>Zonisamide | Drug: zonisamide<br>* flexible dosages of 100-500mg/day<br>* Other names: Zonegran;|
| Placebo Comparator: B<br>placebo | Drug: Placebo<br>* Placebo<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| 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 | 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). | baseline to the end of 12 weeks in treatment | 
| Weekly Rate of Change in Abstinent Days | 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). | baseline to the end of 12 weeks in treatment | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Change in Number of Drinks Per Week by Week | 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). | baseline to the end of 12 weeks in treatment | 
| Change in the Urge to Drink Alcohol as Measured by the Alcohol Urge Questionnaire (AUQ) | 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. | baseline to the end of 12 weeks in treatment | 
| Change in Gamma-glutamyl Transferase (GGT) Concentration | 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. | 12 weeks (from initiation to end of treatment) | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Zonisamide, Pharmacotherapy, Alcohol dependence, anticonvulsant