Topiramate Treatment of Alcohol Use Disorders in African Americans

1. Objective(s): Despite having lower rates of drinking and heavy drinking than European
Americans (EAs), African Americans (AA) have significantly higher rates of mortality
from a variety of alcohol-related conditions, including liver cirrhosis, accidents, and
violence. The current proposal aims to improve alcohol treatment in AA Veterans, who
comprise 12% of the Veteran population.

2. Research Design: The proposed study is a two-arm, randomized 12-week, parallel-groups
comparison of topiramate versus placebo to reduce the frequency of heavy drinking days
and increase the number of abstinent days in 160 AA patients with AUD.

3. Methodology: The following specific aim is used to direct the methods:

Specific Aim 1. To test the efficacy of topiramate (TOP) 200 mg/day in reducing the
frequency of heavy drinking and increasing abstinent days in African-American (AA)
patients with alcohol use disorder (AUD). The investigators hypothesize that, as in
European-Americans (EAs), AA subjects receiving TOP will report fewer heavy drinking
days (HDDs) and more abstinent days than those receiving placebo (PLA).

The analyses make use of all data provided by all patients to estimate models to test
the TOP effect on days of heavy drinking and abstinent days. Power for the contrasts
will be determined by the patterns of outcomes in the final six weeks, so power
estimates are based on weeks 7 through 12 as a 6-week trial, with adjustments for loss
to attrition between baseline and week 6. Based on the investigators' prior study
(Kranzler 2014), the investigators anticipate 92% retention through the first six weeks
for each group, yielding 74 available per group at the end of week 6, an additional 4%
loss due to dropout across the final six weeks, and a within-subject correlation of
about 0.6. The methods of Hedeker et al (1999) show that the investigators will have 80%
power for a TOP main effect size of d=0.40, 0.43, and 0.46, for within-subject
correlations of 0.5, 0.6, and 0.7, respectively, at a corrected alpha level of 0.025.

4. Impact/Significance: The proposal is innovative in that it will focus on AAs with AUD,
an understudied and underserved population for whom no such data currently exist. Given
the far-reaching effects of AUD and its high prevalence among Veterans, added evidence
based treatments may realize reduced health care costs from unnecessary ED visits and
reduced complications of illnesses such as hepatitis C and congestive heart failure.

Inclusion Criteria:

- self-identification as African American

- age 18 to 70 years, inclusive

- average weekly ethanol consumption of >24 standard drinks for men or >18 standard
drinks for women, with a weekly average of > 2 heavy drinking days (men: > 5 standard
drinks; women: > 4 standard drinks) during the month before screening

- a current diagnosis of moderate or severe AUD, i.e.:

- meeting at least 4 of 11 DSM-5 AUD criteria

- expressed goal to reduce or stop drinking

- able to read English at the 8th grade or higher level and without gross cognitive
impairment

- willing to nominate an individual who will know the patient's whereabouts to
facilitate follow up during the study

- women of child-bearing potential, i.e.:

- who have not had a hysterectomy

- bilateral oophorectomy

- tubal ligation or are less than two 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

- willing and able to provide signed, informed consent to participate in the study

Exclusion Criteria:

- a current, clinically significant physical disease or abnormality on the basis of:

- medical history

- physical examination

- or routine laboratory evaluation, including direct bilirubin elevations of >110%
or a transaminase elevation >300% of normal

- history of nephrolithiasis

- history of glaucoma

- current serious psychiatric illness, i.e.:

- schizophrenia

- bipolar disorder

- severe or psychotic major depression

- borderline or antisocial personality disorder

- eating disorder

- or imminent suicide or violence risk

- current moderate-to-severe alcohol withdrawal requiring pharmacological treatment (see
Section D.4.a. regarding alcohol detoxification)

- current DSM-5 diagnosis of drug use disorder (other than nicotine or cannabis)

- a history of hypersensitivity to TOP

- current regular treatment with a psychotropic medication, including medications that,
when combined with alcohol, present a risk of overdose, e.g.:

- chronic opioid use (of note the investigators will allow subjects to discontinue
medications that have no demonstrated therapeutic effect in order to enroll)

- current treatment with TOP or a medication approved for AUD

- considered to be unsuitable candidates for receipt of an investigational drug