Topiramate's Effects on Heavy Drinking
Condition: Alcohol Drinking
MeSH terms: Alcohol Drinking
Intervention: Topiramate; Placebo
Intervention MeSH terms: Topiramate
Phase: Phase 2
Study type: Interventional
Primary purpose: Treatment
Allocation: Randomized
Intervention model: Parallel Assignment
Masking: Double (Participant, Investigator)
Enrollment: 1.0
Sex: All
Minimum age: 18 Years
Maximum age: 60 Years
Healthy volunteers: No

Summary:

      The proposed project will utilize perfusion functional magnetic resonance imaging (fMRI) to
      examine the effects of topiramate on brain and behavioral responses in heavy drinkers to
      appetitive alcohol reminders (cues that motivate continued alcohol use and relapse). This
      project will yield novel findings on brain and behavioral responses to alcohol cues, the
      effects of topiramate on alcohol cue reactivity, and the mechanisms underlying topiramate's
      ability to blunt alcohol cue reactivity and heavy drinking.
    

Eligibility criteria:

        Inclusion Criteria:

          -  Physically healthy, as determined by a comprehensive physical examination and approval
             of the study physician, males or females who drink alcohol, ages 18-60.

          -  Average weekly ethanol consumption of >24 standard drinks for men, or >18 standard
             drinks for women.

          -  Females must be non-pregnant, non-lactating and either be of non-childbearing
             potential (i.e. sterilized via hysterectomy or bilateral tubal ligation or at least 2
             years postmenopausal) or of child bearing potential but practicing a medically
             acceptable method of birth control. Examples of medically acceptable methods for this
             protocol include: the birth control pill, intrauterine device, injection of
             Depo-Provera, Norplant, contraceptive patch, contraceptive ring, double-barrier
             methods (such as condoms and diaphragm/spermicide), male partner sterilization,
             abstinence (and agreement to continue abstinence or to use an acceptable method of
             contraception, as listed above, should sexual activity commence), and tubal ligation.

          -  Provide voluntary informed consent.

          -  Must be able to read. [Subjects are required to be able to read because there are
             several self-administered measures that they must read, understand and provide written
             answers.]

          -  Intelligence quotient of ≥ 80.

        Exclusion Criteria:

          -  Current, clinically significant physical disease or abnormality on the basis of
             medical history, physical examination, or routine laboratory evaluation.

          -  History of head trauma or injury causing loss of consciousness, lasting more than five
             (5) minutes or associated with skull fracture or inter-cranial bleeding or abnormal
             MRI.

          -  Current major DSM-IV Axis I diagnoses other than alcohol use disorder (except nicotine
             use disorder).

          -  Presence of magnetically active irremovable prosthetics, plates, pins, permanent
             retainer, bullets, etc. (unless a radiologist confirms that it's presence is
             unproblematic). An x-ray may be obtained to determine eligibility given the
             possibility of a foreign body.

          -  History of a serious psychiatric illness including psychosis, bipolar disorder, or
             suicidal or homicidal intent.

          -  Current treatment with carbonic anhydrase inhibitors.

          -  Claustrophobia or other medical condition preventing subject from lying in the MRI for
             approximately one (1) hour.

          -  Current regular treatment with psychotropic medications (e.g., benzodiazepines,
             antidepressants), which affect neurotransmitter systems or a medication being used to
             treat alcohol use disorders (e.g., naltrexone, acamprosate).

          -  Vision problems that cannot be corrected with glasses.

          -  Body Mass Index (BMI) greater than or equal to 34, body girth greater than 52 inches
             and a head girth greater than 25 inches.

          -  History of stroke and/or stroke related spasticity.

          -  History of glaucoma or kidney stones.

          -  HIV positive.

          -  History of seizures.

          -  History of topiramate treatment for alcohol use disorder and report no treatment
             response.

          -  Current DSM-5 diagnosis of alcohol use disorder that is clinically too severe to
             permit them to participate in a research trial in which the goal is to stop or reduce
             drinking.