Interdisciplinary Study of A Novel Anticonvulsant in Alcoholism
Condition: Alcohol Dependence
MeSH terms: Alcoholism
Study type: Interventional
Phase: Phase 3

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.
    

Detailed description: 
      Potential participants will complete a telephone and an in-clinic screening to determine
      eligibility for this study. Eligible participants will be randomized to receive one of two
      treatment conditions: 1) Zonisamide plus Take Control (a computerized alcohol reduction and
      medication compliance program developed by the National Institute on Alcohol Abuse and
      Alcoholism (NIAAA)); 2) a placebo plus Take Control. For both conditions, participants will
      receive 12 treatment sessions. Participants will receive medication at each session, and they
      should have two weeks worth of medication on hand at any given time. Participants will take
      the medication as prescribed at home. The first 11 treatment sessions will include Take
      Control. The 12 treatment sessions will be followed by two drug dose taper sessions, and a
      follow up phone interview immediately following the final session.

      Participants will also undergo two scans of less than 2 hours duration, one before they begin
      study sessions and the second near the end of the study (12th study week and before the
      medication taper). At the in-clinic screening session, participants will receive a "MRI
      Information for Research Participants" handout that answers some commonly asked questions
      about MRI and tells participants what they can expect while undergoing an MRI scan. Both
      scans will be conducted at BU CILSE. Participants will be screened before each scan session
      for pregnancy (urine sample, women of childbearing potential only), recent smoking or alcohol
      use (breathalyzers), and illicit substance use (urine sample). Participants will be asked to
      complete the Alcohol Urge Questionnaire (AUQ) before and after the scan. Eligible
      participants will complete a 1-hour 3 Tesla MRI scan involving structural imaging (MRI) and
      functional imaging (fMRI). The fMRI scans include a resting-state scan (no task involved) a
      cognitive (Stroop) task, and an alcohol cue reactivity task. The latter two scans involve
      presentation of visual images to participants while they are in the scanner. No contrast
      agent or invasive procedures are used. Only personnel trained in working in high magnetic
      field environments will work on this project. Imaging data will be analyzed on secure
      networks using only encrypted files. All data obtained will be coded to protect participant
      privacy and confidentiality.

      Starting on March 23, 2020, all study procedures have been moved to HIPAA compliant, remote
      platforms and can be performed from home due to the COVID-19 pandemic. Screenings will take
      place over the phone or Zoom, neurocognitive assessments will take place on Inquisit 5 at
      sessions 1 and 12, female participants of child-bearing potential will be directed to take a
      pregnancy test at all sessions, and patients will use a breathalyzer provided by Boston
      University at the start of each session to show they are within study-specified limits of
      blood alcohol content.

      One month following completion of study treatment (study week 16), participants will be asked
      to complete a follow-up telephone assessment.

      The entire study is estimated to be completed in five years. The first six months to nine
      months of the project will be dedicated to hiring, training and certifying staff. Recruitment
      will begin within three months of obtaining IRB approval, during Year 1 of the study.
      Approximately 3-4 new participants will be recruited per month. We anticipate recruiting a
      total of 5 participants in Year 1, 25 participants in Years 2 and 3, 30 participants in year
      4, and 15 participants in Year 5. The last third of Year 5 will be devoted to completion of
      data entry and data management procedures, preliminary analyses, and the preparation of
      manuscripts
    

Intervention name(s): Zonisamide; Take Control; Placebo (for Zonisamide)
Intervention type(s): Drug; Behavioral; Drug
Intervention description(s): 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.
Other intervention name(s): Zonegran
Intervention MeSH terms: Zonisamide
Allocation: Randomized
Intervention model: Parallel Assignment
Masking: Triple (Participant, Investigator, Outcomes Assessor)
Primary purpose: Treatment