Zonisamide Treatment of Alcohol Use Disorder: an Evaluation of Efficacy and Mechanism of Action
Condition: Alcohol Use Disorder
MeSH terms: Alcoholism; Alcohol Drinking
Intervention: Zonisamide; Placebo
Intervention description: Titration of dose to 500mg oral, daily, over 8 weeks, then 7 weeks of treatment at that dose; Placebo
Intervention MeSH terms: Zonisamide
Phase: Phase 3
Study type: Interventional
Primary purpose: Treatment
Allocation: Randomized
Intervention model: Parallel Assignment
Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
Enrollment: 156.0
Sex: All
Minimum age: 21 Years
Maximum age: 70 Years
Healthy volunteers: No
Keywords: Alcohol Use Disorder; Alcoholism; Alcohol Dependence; Zonisamide; Alcohol Intoxication; Drinking Behaviors; Anticonvulsants

Summary:

      This is a randomized, placebo-controlled, double-blind, 16 week trial of the medication
      zonisamide for the treatment of heavy drinking alcoholic civilians.
    

Eligibility criteria:

        Inclusion Criteria:

          -  Female/male aged 21-70 years

          -  Regular heavy drinkers as defined by averaging 2 heavy drinking days per week over 90
             days baseline pre-treatment timeline follow-back (TLFB), and current DSM-IV-TR alcohol
             dependence that recognize a need to reduce or stop drinking (Note: heavy drinking days
             will be defined as follows; for men greater than or equal to 5 drinks in a day and for
             women greater than or equal to 4 drinks in a day)

          -  Women of child-bearing potential (i.e., no hysterectomy, bilateral oophorectomy, or
             tubal ligation or <2 years postmenopausal), must be non-lactating, practicing a
             reliable method of birth control, and have a negative serum pregnancy test prior to
             initiation of treatment;

          -  Willingness to provide signed, informed consent to participate in the study

        Exclusion Criteria:

          -  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 (i.e., AST and ALT) greater than 300% of the upper
             limit of normal or direct bilirubin levels >150% of the upper limit of normal) on the
             basis of medical history, physical examination, or routine laboratory evaluation.
             Other specific exclusionary disorders include;

          -  History of clinically significant renal calculi or renal failure; a significant
             indication of renal compromise will be defined by an elevation of serum creatinine
             above the investigators' laboratory's limit of normal, or a known history of renal
             failure or chronic renal disease, or any current or chronic disease that could
             reasonably be expected to result in renal failure

          -  History of hypersensitivity to ZNS or any sulfonamide, Stevens-Johnson Syndrome,
             penicillin allergy, or history of any severe drug allergic reaction; History of
             systemic autoimmune disease such as lupus erythematosis, fibromyalgia, or rheumatoid
             arthritis;

          -  Current blood dyscrasia or a history of such, with the exception of a past history of
             iron deficiency anemia

          -  History of seizure disorder

          -  Use of any of a number of medications that might prominently influence drinking
             patterns or cause risk of harm or injury (e.g., topiramate, disulfiram, naltrexone,
             acetazolamide, stimulants such as amphetamine, or tramadol; Schizophrenia, bipolar
             disorder, PTSD, or substantial suicide or violence risk (i.e., can't be managed safely
             in the outpatient setting) on the basis of history or psychiatric examination; j)
             currently dependent on opioids or benzodiazepines or other sedatives

          -  Considered by the investigators to be clinically inappropriate for study participation
             or have participated in another pharmacotherapy study in the past thirty days

          -  Subjects with prominent signs of physical dependence, and/or medical comorbidities
             such that study physicians feel they should consider immediate detoxification, and
             referred for medical detoxification in a normal treatment setting