Clinical trial NCT02900352: Zonisamide Treatment of Alcohol Use Disorder: an Evaluation of Efficacy and Mechanism of Action
Official title: Zonisamide Treatment of Alcohol Use Disorder: an Evaluation of Efficacy and Mechanism of Action
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE3
Conditions: Alcohol Use Disorder
Keywords: Alcohol Use Disorder
Alcoholism
Alcohol Dependence
Zonisamide
Alcohol Intoxication
Drinking Behaviors
Anticonvulsants
Lead sponsor: Virginia Commonwealth University
Sponsor class: OTHER
Collaborators: name: University of Connecticut
name: Yale University
name: National Institute on Alcohol Abuse and Alcoholism (NIAAA)
name: VA Connecticut Healthcare System
First posted: 2016-09-14
Enrollment: 156
Sex: ALL
Minimum age (years): 21
Maximum age (years): 70
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

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.

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

Primary outcomes:
measure: Number of Drinks Per Week
timeFrame: over 8 weeks (weeks 9-16)
Secondary outcomes:
measure: Percentage of Subjects With No Heavy Drinking Days
timeFrame: over the last 8 weeks (weeks 9-16)
measure: Gamma Glutamyl Transferase (GGT) Levels
timeFrame: over 16 weeks (weeks 1-16)
measure: Number of Heavy Drinking Days Per Week
timeFrame: over the last 8 weeks (weeks 9-16)
measure: Change in Alcohol Urge Questionnaire Score (AUQ)
timeFrame: over 16 weeks (weeks 1-16) and at 2 week and 3 month follow up
measure: Change in Quality of Life
timeFrame: over 16 weeks (weeks 1-16) and at 2 week and 3 month follow up
measure: Level of Alcohol-related Problems
timeFrame: over 16 weeks (weeks 1-16) and at 2 week and 3 month follow up
Other outcomes:
Locations:
city: Farmington
country: United States
facility: UCONN Health
state: Connecticut
city: New Haven
country: United States
facility: Yale University
state: Connecticut
city: West Haven
country: United States
facility: West Haven Veterans Affairs
state: Connecticut
city: Richmond
country: United States
facility: Virginia Commonwealth University
state: Virginia
Study officials:
affiliation: Virginia Commonwealth University
name: Albert Arias, MD
role: PRINCIPAL_INVESTIGATOR
References: