The Effects of Zonisamide on Alcohol Dependence
Condition: Alcoholism
MeSH terms: Alcoholism
Intervention: Zonisamide
Intervention description: Week 1 (Wk1) -100 mg daily; Wk 2- 100 mg daily; Wk 3- 200 mg daily; Wk 4- 200 mg daily; Wk 5- 300 mg daily; Wk 6- 300 mg daily; Wk 7-11- 400 mg daily; Wk 12(Days 1-5) 300 mg daily; Wk 12 (Day 6-7) Week 13 (Days 1-3)- 200 mg daily; Week 13 (Days 4-7) - 100 mg daily.
Intervention MeSH terms: Zonisamide
Phase: Phase 2
Study type: Interventional
Primary purpose: Treatment
Allocation: Non-Randomized
Intervention model: Single Group Assignment
Masking: None (Open Label)
Enrollment: 16.0
Sex: All
Minimum age: 21 Years
Maximum age: 64 Years
Healthy volunteers: No
Keywords: Zonisamide; Alcoholism; Alcohol

Summary:

      In this study the influence of zonisamide administration over a 13 week period on alcohol
      consumption in alcoholic (alcohol dependent) subjects will be examined. The dose of
      zonisamide given to subjects will be slowly increased over a period of several weeks. They
      will receive a full dose over a 5 week period. This will be a pilot study in which all of the
      subjects will only receive zonisamide. A primary objective of this study is to determine the
      possible size of the effect that zonisamide administration has on drinking (i.e. drinks
      consumed per day) to allow us to plan for a larger clinical trial of the effects of
      zonisamide on alcohol dependence.
    

Eligibility criteria:

        INCLUSION CRITERIA

        To be admitted into this study patients must meet the following criteria:

          1. DSM IV TR Diagnosis of Alcohol Dependence; minimal level of 14 drinks per week for
             women or 21 drinks per week for men over a 28 day consecutive period during the 90 day
             period prior to the screening session.

          2. Male or Female 21-64 years of age.

          3. Able to provide informed consent and comprehend study procedures.

          4. Negative urine toxicological screen for opioids, psychomotor stimulants,
             sedative-hypnotics, and cannabinoids. If the urine tox screen was positive for any
             substance it may be repeated within two weeks.

          5. Score of >8 on the Alcohol Use Disorder Identification Test (AUDIT) during screening.

          6. Must be suitable for outpatient management of alcoholism.

          7. Express desire to stop drinking or reduce alcohol consumption with a possible
             long-term goal of abstinence.

          8. Provide contact information for themselves or an alternate contact that the staff will
             call in case of missed appointment.

          9. Women must be postmenopausal for at least one year, be surgically sterile, be using an
             effective method of birth control (e.g. contraceptive injection, intrauterine device,
             spermicide with barrier, contraceptive patch, contraceptive ring, male partner
             sterilization, oral contraceptives) or completely abstinent (and agree to use one of
             the above mentioned methods of contraception if sexual activity is ever initiated).

         10. Must be able to take oral medications, adhere to the regimen and be willing to return
             for follow up visits.

         11. Must have breath alcohol concentration of no more than 0.01% when the informed consent
             is provided and the consent form is signed.

         12. Must have resided at the same address for at least 3 months.

        EXCLUSION CRITERIA

        Patients meeting the following criteria will be excluded from the study:

          1. Dependent on or extensive abuse of drugs or substances other than ethanol, nicotine,
             or caffeine.

          2. DSM IV-TR diagnosis of any current Axis I diagnosis other than alcohol dependence,
             nicotine dependence, or caffeine dependence that in the opinion of the study
             physicians might require intervention with either pharmacological or
             non-pharmacological therapy that will interfere with the course of the study.

          3. Receiving inpatient or outpatient treatment for alcohol dependence (with the exception
             of AA or other self-help groups) within 4 weeks prior to enrollment into this study.

          4. Subjects with a score of 10 or greater on the CIWA-Ar (a withdrawal scale) on first or
             second visits.

          5. Currently being treated with acamprosate, disulfiram or naltrexone.

          6. Currently being treated with any of the following medications: a) Antipsychotic
             agents- including clozapine, risperidone, quetiapine, haloperidol b) Antimanic or
             anticonvulsant agents- including lithium carbonate, phenytoin, phenobarbital,
             carbamazepine, topiramate, valproic acid, divalproex, tiagabine c) Sedative-hypnotic
             or antianxiety agents-including triazolam, temazepam, zolpidem, zalepron, buspirone,
             alprazolam, diazepam, clonazepam, oxazepam, lorazepam d) chronic opioid treatment-
             including methadone, buprenorphine, oxycodone, morphine e) Psychomotor stimulants-
             amphetamine derivatives, methylphenidate

          7. Subjects who are legally mandated to participate in an alcohol treatment program

          8. Use of any medication known to inhibit or induce cytochrome P450 3A4 enzymes including
             macrolide antibiotics, fluoxetine, and carbamazepine.

          9. Subjects who have attempted suicide or who have had suicidal ideation within 30 days
             of their first visit as assessed using responses from the SCID and Hamilton Depression
             scale.

         10. Subjects with renal disease (including severe infection and cancer), impaired renal
             clearance (CrCl less than 50 ml/min), or history of kidney stones.

         11. Subjects with AST or ALT >3 times the upper limit of the normal range during
             screening.

         12. History of significant neurological disorder, including a history of seizures, stroke,
             dementia, multiple sclerosis, Parkinson's disease, brain tumors, or encephalitis.

         13. Subjects who are pregnant (as assessed by serum HCG) or lactating.

         14. Subjects known to have clinically significant medical conditions. These may include:
             symptomatic CAD or PVD, malignancy or history of malignancy in the last 5 years,
             significant pulmonary disease or endocrinological disorders.

         15. Subjects with prior hypersensitivity to zonisamide or related compounds, including
             sulfonamides (e.g. sulfisoxazole) carbonic anhydrase inhibitors (e.g. acetazolamide),
             sulfonylureas (e.g. chlorpropamide), sulfamates (e.g. topiramate), thiazide (e.g.
             hydrochlorothiazide), and loop diuretics (e.g. furosemide) except ethacrycrynic acid.

         16. Subjects who in the opinion of the study physicians should not be enrolled based on
             the precautions, warnings, and contraindications stated on the package insert for
             zonisamide.

         17. Impending incarceration.

         18. Score of 25 or less on the Folstein Mini-Mental examination.

         19. History of anticonvulsant-induced rash.