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

NCT ID: NCT02900352

Last Updated: 2022-10-13

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: PHASE3
• Total Enrollment: 156 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2016-10-31
• Study Completion Date: 2021-04-22

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.

Detailed Description

This is a 16-week randomized, double blind, placebo-controlled trial designed to determine the effectiveness of zonisamide treatment for reducing heavy drinking and overall drinking in 160 treatment-seeking, regularly heavy drinking, alcohol-dependent civilians who want to quit drinking or reduce consumption to non-hazardous levels. The investigators will use state-of-the-art methodology and outcome assessments, including medical management (MM) therapy (a minimal behavioral intervention aimed at reinforcing treatment goals and adherence to medication), which is simple and easily implemented in primary care settings. The use of MM in the study will increase the generalizability of results, allowing a more accurate assessment of zonisamide's effectiveness than if a more intensive behavioral intervention were to be used. To demonstrate zonisamide's effectiveness in a representative civilian sample, the investigators will include civilians with co-morbid mood and anxiety disorders.

Conditions

Alcohol Use Disorder

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: PARALLEL
• Primary Study Purpose: TREATMENT
• Blinding Strategy: QUADRUPLE

Study Groups

Zonisamide

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.

Group Type: EXPERIMENTAL

Zonisamide

Intervention Type: DRUG

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

Placebo

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)

Group Type: PLACEBO_COMPARATOR

Placebo

Intervention Type: DRUG

Placebo

Interventions

Zonisamide

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

Intervention Type: DRUG

Placebo

Placebo

Intervention Type: DRUG

Other Intervention Names

Brand name: Zonegran; Brand name: Zonegran

Eligibility Criteria

Inclusion Criteria

• 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

Exclusion Criteria

• A current, clinically significant physical disease or abnormality (i.e., neurologic, renal, rheumatologic, gastrointestinal, hematologic, pulmonary, endocrine, cardiovascular, hepatic, or autoimmune disease that, in the context of the study would represent a risk to the subject, or significant laboratory abnormalities such as hepatic aminotransferase levels (i.e., AST and ALT) greater than 300% of the upper limit of normal or direct bilirubin levels >150% of the upper limit of normal) on the basis of medical history, physical examination, or routine laboratory evaluation. Other specific exclusionary disorders include;
• 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

• Minimum Eligible Age: 21 Years
• Maximum Eligible Age: 70 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

University of Connecticut

OTHER

Sponsor Role: collaborator

Yale University

OTHER

Sponsor Role: collaborator

National Institute on Alcohol Abuse and Alcoholism (NIAAA)

NIH

Sponsor Role: collaborator

VA Connecticut Healthcare System

FED

Sponsor Role: collaborator

Virginia Commonwealth University

OTHER

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

Albert Arias, MD

Role: PRINCIPAL_INVESTIGATOR

Virginia Commonwealth University

Locations

UCONN Health

Farmington, Connecticut, United States

Yale University

New Haven, Connecticut, United States

West Haven Veterans Affairs

West Haven, Connecticut, United States

Virginia Commonwealth University

Richmond, Virginia, United States

Countries

United States

Provided Documents

Document Type: Study Protocol and Statistical Analysis Plan

View Document

Document Type: Informed Consent Form

View Document

Other Identifiers

1605017700

Identifier Type: OTHER

Identifier Source: secondary_id

7R01AA024466-04

Identifier Type: NIH

Identifier Source: secondary_id

View Link

HM20014185

Identifier Type: -

Identifier Source: org_study_id