Clinical trial NCT00595556: Zonisamide vs. Placebo in the Treatment of Alcohol Dependence
Official title: Zonisamide vs. Placebo in the Treatment of Alcohol Dependence
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE4
Conditions: Alcoholism
Alcohol Abuse
Alcohol Dependence
Keywords: Zonisamide
Pharmacotherapy
Alcohol dependence
anticonvulsant
Lead sponsor: UConn Health
Sponsor class: OTHER
Collaborators: name: National Institute on Alcohol Abuse and Alcoholism (NIAAA)
name: National Center for Research Resources (NCRR)
First posted: 2008-01-16
Enrollment: 40
Sex: ALL
Minimum age (years): 18
Maximum age (years): 65
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief summary: This is a pilot study designed to examine the potential efficacy and tolerability of zonisamide compared to placebo for the treatment of alcohol dependence.

Detailed description: Zonisamide is an antiepileptic medication which has similar clinical and pharmacologic effects to topiramate, a medication that has demonstrated efficacy in a randomized clinical trial for treatment of alcoholism. Because zonisamide is potentially better tolerated and easier to titrate in the outpatient setting than topiramate, it may offer important clinical advantages in the treatment of alcoholism.

This is a small 12-week placebo-controlled pilot study examining tolerability and potential efficacy in anticipation of a larger, placebo-controlled trial of zonisamide for treatment of alcohol dependence. It is a randomized, double-blind trial of zonisamide vs. placebo at flexible dosages of 100-500mg/day in alcoholics receiving ambulatory psychosocial treatment. Participants will take part in six individual Cognitive-Behavioral based therapy sessions, which are focused on learning coping skills. Participants must endorse a goal of either cutting down their drinking to non-hazardous levels, or abstinence.

Eligibility criteria: Inclusion Criteria:

* age 18 to 65 years, inclusive
* current Diagnostic \& Statistical Manual of Mental Disorders 4th ed (DSM-IV) alcohol dependence (within the past month)
* have 2 heavy drinking days per week during the period between screening and baseline (defined as \>4 standard drinks per day for males, and \>3 standard drinks per day for females)
* able to read at the eighth grade or higher level and show no evidence of significant cognitive impairment
* if a woman of child-bearing potential (i.e., who has not had a hysterectomy, bilateral oophorectomy, tubal ligation or who is less than two years postmenopausal), must be non-lactating, practicing a reliable method of birth control including barrier method; and have a negative serum pregnancy test prior to initiation of treatment
* be willing to provide signed, informed consent to participate in the study

Exclusion Criteria:

* have 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 greater than 300% of the uper limit of normal or direct bilirubin levels 150% of the upper limit of normal) on the basis of medical history, physician examination, or routine laboratory evaluation. Serum creatinine level of \> 1.2 mg/dl will also be exclusionary. Other specific exclusionary disorders include:

  * patients with a history of renal calculi
  * patients with a history of hypersensitivity to zonisamide or any sulfonamide, Stevens-Johnson Syndrome, penicillin allergy, or history of any severe drug allergic reaction
  * patients with a significant history of systemic autoimmune disease such as lupus erythematosis, fibromyalgia, or rheumatoid arthritis
  * patients with a current blood dyscrasia or a history of such, with the exception of a remote history of iron deficient anemia
* have a serious psychiatric illness (i.e., schizophrenia, bipolar disorder, severe or psychotic major depression, panic disorder, or substantial suicide or violence risk) on the basis of history or psychiatric examination
* current dependence on opioids or benzodiazepines or other sedatives will also be exclusionary
* are considered by investigators to be clinically inappropriate for study participation
* because individuals with a history of seizure disorder could potentially be at increased risk of experiencing a seizure due to their drinking, such individuals will also be excluded
* have participated in another pharmacotherapy study in the past thirty days

Primary outcomes:
measure: Change in Number of Heavy Drinking Days (i.e., 5 or More Drinks Per Day for Men, and 4 or More Per Day for Women)Per Week, by Week
timeFrame: baseline to the end of 12 weeks in treatment
measure: Weekly Rate of Change in Abstinent Days
timeFrame: baseline to the end of 12 weeks in treatment
Secondary outcomes:
measure: Change in Number of Drinks Per Week by Week
timeFrame: baseline to the end of 12 weeks in treatment
measure: Change in the Urge to Drink Alcohol as Measured by the Alcohol Urge Questionnaire (AUQ)
timeFrame: baseline to the end of 12 weeks in treatment
measure: Change in Gamma-glutamyl Transferase (GGT) Concentration
timeFrame: 12 weeks (from initiation to end of treatment)
Other outcomes:
Locations:
city: Farmington
country: United States
facility: University of Connecticut Health Center
state: Connecticut
Study officials:
affiliation: UConn Health
name: Albert J. Arias, MD
role: PRINCIPAL_INVESTIGATOR
References: