Clinical trial NCT02368431: Effectiveness of Zonisamide in Alcohol Dependent Veterans
Official title: Effectiveness of Zonisamide in the Treatment of Alcohol Dependent Veterans
Study type: INTERVENTIONAL
Overall status: TERMINATED
Phase: PHASE3
Conditions: Alcohol Use Disorder
Keywords: Alcohol Use Disorder
Alcoholism
Alcohol Dependence
Zonisamide
Alcoholic Intoxication
Drinking Behaviors
Anticonvulsants
Lead sponsor: VA Office of Research and Development
Sponsor class: FED
First posted: 2015-02-23
Enrollment: 92
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 Veterans.

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 Veterans 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 Veteran sample, the investigators will include Veterans with co-morbid mood and anxiety disorders.

The investigators also plan to explore the interaction between genotype and medication on drinking outcomes.

Eligibility criteria: Inclusion Criteria:

* Female/male veterans 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 alcohol dependence diagnosis by the Diagnostic and Statistical Manual IV Text Revision (DSM-IV-TR) 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 \[i.e., aspartate aminotransferase (AST) and alanine aminotransferase (ALT)\] 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 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 zonisamide 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, posttraumatic stress 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 (PSNHDD)
timeFrame: Baseline
measure: Gamma Glutamyl Transferase (GGT)
timeFrame: Baseline, Week 4, 8 and 16
measure: Number of Heavy Drinking Days Per Week
timeFrame: over 16 weeks (weeks 1-16)
measure: Alcohol Urge Questionnaire Score (AUQ)
timeFrame: over 16 weeks (weeks 1-16)
measure: Change in Quality of Life
timeFrame: Over 16 weeks (Baseline and 16 weeks)
measure: Level of Alcohol-related Problems (SIP)
timeFrame: over 16 weeks (Baseline and Week 16)
Other outcomes:
Locations:
city: West Haven
country: United States
facility: VA Connecticut Healthcare System West Haven Campus, West Haven, CT
state: Connecticut
Study officials:
affiliation: VA Connecticut Healthcare System West Haven Campus, West Haven, CT
name: Albert J Arias, MD
role: PRINCIPAL_INVESTIGATOR
References: