Zonisamide Treatment of Alcohol Use Disorder: an Evaluation of Efficacy and Mechanism of Action

NCT02900352 | Completed Phase 3 Results DMC

• 3 other identifiers: HM2001418516050177007R01AA024466-04
• Study Type: interventional
• Target: 156
• Locations: 1 country
• Sites: 4

Brief Summary

This is a randomized, placebo-controlled, double-blind, 16 week trial of the medication zonisamide for the treatment of heavy drinking alcoholic civilians.

Conditions

Alcohol Use Disorder

Keywords

Alcohol Use Disorder; Alcoholism; Alcohol Dependence; Zonisamide; Alcohol Intoxication; Drinking Behaviors; Anticonvulsants

Outcome Measures

Primary Outcomes (1)

• Number of Drinks Per Week

  Difference between groups in the number of total standard drinks per week over 8 weeks (weeks 9-16, the weeks on the target dose) performed using a mixed models longitudinal analysis.

  over 8 weeks (weeks 9-16)

Secondary Outcomes (6)

• Percentage of Subjects With No Heavy Drinking Days

  over the last 8 weeks (weeks 9-16)

• Gamma Glutamyl Transferase (GGT) Levels

  over 16 weeks (weeks 1-16)

• Number of Heavy Drinking Days Per Week

  over the last 8 weeks (weeks 9-16)

• Change in Alcohol Urge Questionnaire Score (AUQ)

  over 16 weeks (weeks 1-16) and at 2 week and 3 month follow up

• Change in Quality of Life

  over 16 weeks (weeks 1-16) and at 2 week and 3 month follow up

Study Arms (2)

Zonisamide

EXPERIMENTAL

Subjects will receive zonisamide titrated to a target dose of 500mg orally, daily, double-blind (Titration of dose to 500mg oral, daily, over 7 weeks, then 9 weeks of treatment at that dose). Subjects may increase their dose to 600mg daily during the target treatment period if it is thought to be beneficial.

Drug: Zonisamide

Placebo

PLACEBO COMPARATOR

Patients will receive placebo pills that are made to match the zonisamide medication (via over-encapsulation, double-blind, subjects will receive same number of capsules as the active medication group)

Drug: Placebo

Interventions

Zonisamide DRUG

Titration of dose to 500mg oral, daily, over 8 weeks, then 7 weeks of treatment at that dose

Also known as: Brand name: Zonegran

Zonisamide

Placebo DRUG

Placebo

Also known as: Brand name: Zonegran

Placebo

Eligibility Criteria

• Age: 21 Years - 70 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Female/male aged 21-70 years
• Regular heavy drinkers as defined by averaging 2 heavy drinking days per week over 90 days baseline pre-treatment timeline follow-back (TLFB), and current DSM-IV-TR alcohol dependence that recognize a need to reduce or stop drinking (Note: heavy drinking days will be defined as follows; for men greater than or equal to 5 drinks in a day and for women greater than or equal to 4 drinks in a day)
• Women of child-bearing potential (i.e., no hysterectomy, bilateral oophorectomy, or tubal ligation or \<2 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;
• Willingness to provide signed, informed consent to participate in the study

You may not qualify if:

• History of clinically significant renal calculi or renal failure; a significant indication of renal compromise will be defined by an elevation of serum creatinine above the investigators' laboratory's limit of normal, or a known history of renal failure or chronic renal disease, or any current or chronic disease that could reasonably be expected to result in renal failure
• History of hypersensitivity to ZNS or any sulfonamide, Stevens-Johnson Syndrome, penicillin allergy, or history of any severe drug allergic reaction; History of systemic autoimmune disease such as lupus erythematosis, fibromyalgia, or rheumatoid arthritis;
• Current blood dyscrasia or a history of such, with the exception of a past history of iron deficiency anemia
• History of seizure disorder
• Use of any of a number of medications that might prominently influence drinking patterns or cause risk of harm or injury (e.g., topiramate, disulfiram, naltrexone, acetazolamide, stimulants such as amphetamine, or tramadol; Schizophrenia, bipolar disorder, PTSD, or substantial suicide or violence risk (i.e., can't be managed safely in the outpatient setting) on the basis of history or psychiatric examination; j) currently dependent on opioids or benzodiazepines or other sedatives
• Considered by the investigators to be clinically inappropriate for study participation or have participated in another pharmacotherapy study in the past thirty days
• Subjects with prominent signs of physical dependence, and/or medical comorbidities such that study physicians feel they should consider immediate detoxification, and referred for medical detoxification in a normal treatment setting

Sponsors & Collaborators

• Virginia Commonwealth University: lead
• University of Connecticut: collaborator
• Yale University: collaborator
• National Institute on Alcohol Abuse and Alcoholism (NIAAA): collaborator
• VA Connecticut Healthcare System: collaborator

Study Sites (4)

UCONN Health

Farmington, Connecticut, 06030, United States

Location

Yale University

New Haven, Connecticut, 06520, United States

Location

West Haven Veterans Affairs

West Haven, Connecticut, 06515, United States

Location

Virginia Commonwealth University

Richmond, Virginia, 23298, United States

Location

MeSH Terms

Conditions

Alcoholism; Alcoholic Intoxication; Drinking Behavior

Interventions

Zonisamide

Condition Hierarchy (Ancestors)

Alcohol-Related Disorders; Substance-Related Disorders; Chemically-Induced Disorders; Mental Disorders; Behavior

Intervention Hierarchy (Ancestors)

Sulfonamides; Amides; Organic Chemicals; Sulfones; Sulfur Compounds; Isoxazoles; Azoles; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds

Results Point of Contact

• Title: Dr. Albert Arias
• Organization: Virginia Commonwealth University

albert.arias@vcuhealth.org

8048285793

Study Officials

• Albert Arias, MD

  Virginia Commonwealth University

  PRINCIPAL INVESTIGATOR

Publication Agreements

• PI is Sponsor Employee: Yes

Study Design

• Study Type: interventional
• Phase: phase 3
• Allocation: RANDOMIZED
• Masking: QUADRUPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR, OUTCOMES ASSESSOR
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: September 9, 2016
• First Posted: September 14, 2016
• Study Start: October 1, 2016
• Primary Completion: April 22, 2021
• Study Completion: April 22, 2021
• Last Updated: October 13, 2022
• Results First Posted: October 13, 2022

Record last verified: 2022-10

Data Sharing

• IPD Sharing: Will not share

Locations

US (4)