Topiramate Treatment of Hazardous and Harmful Alcohol Use in Veterans With TBI

Inclusion criteria

• Male and female veterans.
• Ages 18 to 65 (inclusive).
• TBI: a history of mild traumatic brain injury, as defined by American Congress of Rehabilitation Medicine (ACRM) and VA, in the chronic, stable phase of recovery (>6 months from injury). The ACRM defines mild TBI as a traumatically-induced physiological disruption of brain function as demonstrated by at least one of the following:

3.a. loss of consciousness of up to 30 minutes;

3.b. any loss of memory for events immediately before or after the event;

3.c. any alteration in mental state at the time of the event, for example feeling dazed, disoriented, or confused; and

3.d. a focal neurological deficit or deficits that may or may not have been transient, for example loss of coordination, speech difficulties, or double vision. ACRM's definition further specifies that a person may be designated as having a mild TBI only if the severity of the injury does not include a loss of consciousness that lasted longer than 30 minutes, and post-traumatic amnesia lasting longer than 24 hours.

Rationale:

• This is the most common description of patients currently served by our VA facilities.
• Studies at this stable phase will facilitate detection of otherwise subtle changes as findings are less likely to be confounded by 'spontaneous' recovery.

• Current (past month) hazardous alcohol use or harmful alcohol use.

4.a. Hazardous use is drinking that must meet criteria for "at-risk" or "heavy" drinking by National Institute on Alcohol Abuse and Alcoholism (NIAAA) criteria: Subjects must report current (past 30 day) "at-risk" or "heavy" drinking on an average weekly basis, consisting of an average of 15 or more standard drinks per week for men and 8 or more standard drinks per week for women during the 30 days prior to Screening Visit 1 as measured by the Alcohol Timeline Followback (TLFB) method.

4.b. Harmful use is drinking behavior that meets Diagnostic and Statistical Manual (DSM)-IV diagnostic criteria for an Alcohol Use Disorder (Alcohol Dependence or Alcohol Abuse).

• Subjects must express a desire to reduce or stop alcohol use.

• Female subjects must have a negative urine pregnancy test and must be either postmenopausal for at least 1 year or practicing an effective method of birth control (e.g., surgically sterile, spermicide with barrier, male partner sterilization; or absent and agrees to continue abstinence or to use an acceptable method of contraception, as listed above, should sexual activity commence).

• Subjects must have a Breath Alcohol Concentration (BAC) of less than 0.02% when signing the informed consent form.

Exclusion criteria

• Psychotic disorders, bipolar disorders, dementia, or other psychiatric disorders judged to be unstable.
• Subjects known to have clinically significant unstable medical conditions, including but not limited to: Clinically significant renal disease and/or impaired renal function as defined by clinically significant elevation of blood urea nitrogen (BUN) or creatinine or an estimated creatinine clearance of < 60 mL/min; AST and/or ALT > 5 times the upper limit of the normal range and/or a serum bilirubin > 2 times the upper limit of normal.
• History of glaucoma.
• History of kidney stones.
• Concurrent participation in another alcohol treatment study or any study involving medications.
• Female patients who are pregnant or lactating.
• Topiramate use in the past week prior to study entry.
• Use of medications for alcohol dependence (disulfiram, naltrexone, or acamprosate) within the past week.
• Needing acute medical detoxification from alcohol based on a score of 12 or more on the Clinical Institute Withdrawal Assessment of Alcohol Scale (CIWA-AD).
• Subjects who are legally mandated to participate in an alcohol treatment program.
• Subjects who have had a suicide attempt in the past 6 months or suicidal ideation, with intent, in the 30 days prior to enrollment.
• Subjects who have previously been treated with topiramate for any reason and discontinued treatment due to an adverse event or due to a hypersensitivity reaction to topiramate.
• Subjects with seizure disorders.
• Subjects currently being treated with another anticonvulsant.
• Subjects who in the opinion of the investigator should not be enrolled in the study because of the precautions, warnings or contraindications outlined in the topiramate package insert.