Interdisciplinary Study of A Novel Anticonvulsant in Alcoholism
Condition: Alcohol Dependence
MeSH terms: Alcoholism
Intervention: Zonisamide; Take Control; Placebo (for Zonisamide)
Intervention description: ZONEGRAN® (zonisamide) is an antiseizure drug chemically classified as a sulfonamide and unrelated to other antiseizure agents. A dose of 400 mg daily will be used as the target maintenance dose in this study but dosing will be modified if needed to adjust for subject tolerance of drug dosing.; Take Control is a seven module computer-based intervention which presents evidence-based alcohol education that includes motivational interviewing and cognitive-behavioral skills building. This program is derived from the National Institute on Alcohol Abuse and Alcoholism's (NIAAA's) self-help approach, Rethinking Drinking.
Starting on March 23, 2020, participants will participate in a simplified Take Control treatment at home due to the COVID-19 pandemic; Sugar pills manufactured to mimic Zonisamide capsules.
Intervention MeSH terms: Zonisamide
Phase: Phase 3
Study type: Interventional
Primary purpose: Treatment
Allocation: Randomized
Intervention model: Parallel Assignment
Masking: Triple (Participant, Investigator, Outcomes Assessor)
Enrollment: 81.0
Sex: All
Minimum age: 21 Years
Maximum age: 65 Years
Healthy volunteers: No

Summary:

      Alcoholism is the third leading cause of preventable death in the US, accounting for 80,000
      deaths annually. Almost 18 million US adults have alcohol use disorder (AUD); however,
      approved medications for the treatment of AUD has shown limited effectiveness.

      Zonisamide (ZON), a broad spectrum anticonvulsant, has proven to be more effective than a
      placebo in reducing alcohol intake in individuals with alcohol dependence. ZON's mechanism of
      action seems to be quite distinct from currently approved anti-alcoholism medications, which
      holds promise for treatment of individuals who are not responsive to conventional
      medications. However, much remains unknown about ZON's therapeutic mechanisms and ZON's
      efficacy in treating patients with a diagnosis of AUD.

      To fill in these gaps, the investigators will conduct a double-blind randomized controlled
      study that assesses ZON's treatment mechanisms and effectiveness in reducing alcohol
      consumption in patients with AUD. Participants will be randomized to one of two conditions:
      1) treatment with ZON and a computerized psychotherapy platform called Take Control (TC); 2)
      treatment with a placebo (PLC) and TC. To understand the neurobiology behind ZON's potential
      therapeutic effects on AUD, fMRI will be used to compare the brain activity of the ZON+TC
      versus PLC+TC group while participants perform an alcohol and emotional-word Stroop task, as
      well as an alcohol related cues task.
    

Eligibility criteria:

        Inclusion Criteria:

          -  DSM-5 diagnosis of an Alcohol Use Disorder (AUD)

          -  Adults ages 21 to 65 years old

          -  Expressed desire to stop drinking alcohol completely or to reduce alcohol consumption

          -  Reported drinking an average of at least 14 standard drinks per week for males, or 7
             for females occurring over a 28-consecutive day period during the 90 day-long time
             window that preceded the screening session

          -  Must be willing to discontinue psychotherapy for substance use disorder (except A.A.)

        Exclusion Criteria:

          -  Bipolar disorder, schizophrenia, current bulimia/anorexia, dementia, or other
             substance use disorder, with the exception of nicotine, marijuana, and caffeine

          -  Clear and current suicidal risk

          -  Significant medical problem (e.g. uncontrolled diabetes)

          -  Medical contraindication to the use of ZON (e.g. history of significant renal disease,
             kidney stones, liver problems, metabolic acidosis, etc), as indicated by the FDA
             Zonisamide medication guide

          -  History of anticonvulsant-induced rash

          -  Currently taking:

               1. acamprosate, naltrexone, topiramate, disulfiram, or benzodiazepines

               2. a medication that is a moderate or major inhibitor or inducer of cytochrome P450
                  3A4 enzymes

               3. an amphetamine or other psychomotor stimulant

               4. opioids or have been treated chronically with opioids

               5. antipsychotic agents, anticonvulsants, or sedative hypnotics

               6. drugs with "sulfa" moiety (e.g. sulfonamides, sulfonylureas, carbonic anhydrase
                  inhibitors, thiazides, and loop diuretics), except ethacrynic acid

               7. anxiolytics or antidepressants

          -  Previously received ZON for the treatment of an AUD

          -  Known allergy to sulfonamides

          -  Implantation of anything containing magnetically sensitive material including metal
             plates, aneurysm clips, and cardiac pacemakers, stents

          -  Non-English speakers

          -  Pregnant women or women who are lactating (breastfeeding)

        Exclusion from Screening:

          -  Reduction in the mean number of drinks consumed per week for the pre-screening period
             by 50% or more during the screening period or report of average drinks per day fall
             within safe levels of alcohol consumption (i.e. 2 drinks/day for males and 1 drink/day
             for females by the HHS standard) two weeks prior to screening

          -  Women of child bearing potential (not postmenopausal for at least one year) will not
             be admitted into this study unless they are found to have a negative HCG test during
             screening. If they pass the HCG screening, they will be asked to maintain the use of
             an effective means of contraception during the course of the study

          -  Blood test shows lower than average red or white blood cell count or higher than
             average level of acid in blood