Interdisciplinary Study of Two Novel Anticonvulsants in Alcoholism
Condition: Alcoholism; Alcohol Dependence; Alcohol Abuse
MeSH terms: Alcoholism
Intervention: Topiramate; Zonisamide; Levetiracetam; Sugar Pill
Intervention description: Topiramate will be administered orally twice daily beginning on Day 1, Week 1 and continue through Day 7, Week 14. Subjects will be dose titrated as tolerated to a target doses 300 mg topiramate.; Zonisamide will be administered orally twice daily beginning on Day 1, Week 1 and continue through Day 7, Week 14. Subjects will be dose titrated as tolerated to a target doses of 2000 400 mg of zonisamide.; Levetiracetam will be administered orally twice daily beginning on Day 1, Week 1 and continue through Day 7, Week 14. Subjects will be dose titrated as tolerated to a target doses of 2000 mg levetiracetam capsules.; Matched placebo will be administered orally twice daily beginning on Day 1, Week 1 and continue through Day 7, Week 14.
Intervention MeSH terms: Topiramate; Zonisamide; Levetiracetam
Phase: Phase 2
Study type: Interventional
Primary purpose: Treatment
Allocation: Randomized
Intervention model: Parallel Assignment
Masking: Double (Participant, Investigator)
Enrollment: 85.0
Sex: All
Minimum age: 21 Years
Maximum age: 65 Years
Healthy volunteers: No
Keywords: Alcoholism; Alcohol Dependence; Alcohol Abuse; Substance Abuse; Alcoholic Intoxication

Summary:

      This is a double-blind, placebo-controlled, parallel group design study with 4 treatment
      groups; levetiracetam, zonisamide, topiramate, and placebo control. Subjects will receive
      study medications for 14 weeks. Potential subjects will be initially screened for interest in
      study participation and alcohol consumption level to determine basic eligibility by
      telephone, or in person. Individuals who meet telephone screening criteria will be scheduled
      for a clinic appointment to obtain informed consent and conduct screening assessments.
      Subjects who report average drinks per day that are within the guidelines for safe levels of
      alcohol consumption (i.e. 2 drinks/ day males; 1 drink/day females-HHS standard) in the two
      weeks prior to screening will be excluded. Subjects meeting screening criteria will be
      scheduled for a second randomization visit. During this visit baseline assessments will be
      obtained. Eligible subjects will then be randomized to a treatment group and will be provided
      with the first week's study medications. The goal is to directly compare the efficacy and
      tolerability of two novel anticonvulsants, zonisamide and levetiracetam, with placebo, and
      using topiramate, which has extensive evidence supporting its efficacy in alcoholism, as a
      positive control group. We believe that this will be the first direct comparison of these
      agents in alcoholism, and the results will provide information on the efficacy and safety of
      the medications.
    

Eligibility criteria:

        Inclusion Criteria:

        To be admitted into this study candidates must meet the following criteria:

          1. DSM-IV-TR Diagnosis of Alcohol Dependence.

          2. A minimal level of an average of 28 standard drinks per week for women or 35 drinks
             per week for men over a baseline 28 day consecutive period prior to the screening
             session during the 90 day time line follow-back.

          3. Male or Female 21- 65 years of age.

          4. Able to provide informed consent and comprehend study procedures.

          5. Negative urine toxicological screen for opioids, cocaine, amphetamines,
             methamphetamine, and benzodiazepines. The test may be repeated for opioids or
             benzodiazepines shown to be medically prescribed for an acute disorder. The urine test
             may also be repeated if the Investigator deems necessary.

          6. A score of >8 on the Alcohol Use Disorder Identification Test (AUDIT) during
             screening.

          7. Must be suitable for outpatient management of alcoholism.

          8. Express desire to stop drinking or reduce alcohol consumption.

          9. Provide contact information for themselves or an alternate contact that the staff will
             call in case of missed appointment.

         10. Women must be postmenopausal for at least one year, be surgically sterile, or be using
             an effective method of birth control.

         11. Must be able to take oral medications, adhere to the regimen and be willing to return
             for follow up visits.

        Exclusion Criteria:

        Subjects meeting the following criteria will be excluded from the study:

          1. Dependent on DSM IV-TR 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 treatment for alcohol dependence, other then alcohol
             detoxification, within 4 weeks prior to enrollment into this study.

          4. Subjects with a score of 10 or greater on the Clinical Institute Withdrawal Assessment
             for Alcohol-Revised on first or second visits.

          5. Being treated with acamprosate, disulfiram or naltrexone within two weeks prior to
             randomization:

          6. Currently being treated with any of the following medications: a) antipsychotic
             agents. b) antimanic or anticonvulsant agents. c) sedative- hypnotics. d) chronic
             opioid treatment. 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.

          9. Subjects who have attempted suicide or who have had suicidal ideation within 30 days
             of their first visit.

         10. Subjects with renal disease 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.

         13. Subjects who are pregnant (as assessed by serum HCG) or lactating.

         14. Subjects known to have clinically significant medical conditions that in the opinion
             of the study physician would preclude administration of the study medications or limit
             participation in the clinical trial.

         15. Subjects with history of treatment with levetiracetam, topiramate or zonisamide.

         16. Score of 25 or less on the Folstein Mini- Mental examination.

         17. History of anticonvulsant-induced rash.

         18. Taking drugs that contain "sulfa" moiety, such as sulfonamides, sulfonylureas,
             carbonic anhydrase inhibitors, thiazides, and loop diuretics (except ethacrynic acid).

         19. During the 2 weeks prior to screening subjects who report average drinks per day that
             are within the guidelines for safe levels of alcohol consumption (i.e. 2 drinks/ day
             males; 1 drink/day females-HHS standard) will be excluded.

         20. Subjects with a sulfa allergy.

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