The Effects of Zonisamide on Alcohol Dependence

This study has been completed.
Sponsor:
Information provided by:
Boston University
ClinicalTrials.gov Identifier:
NCT00406692
First received: November 30, 2006
Last updated: May 6, 2010
Last verified: May 2010
  Purpose

In this study the influence of zonisamide administration over a 13 week period on alcohol consumption in alcoholic (alcohol dependent) subjects will be examined. The dose of zonisamide given to subjects will be slowly increased over a period of several weeks. They will receive a full dose over a 5 week period. This will be a pilot study in which all of the subjects will only receive zonisamide. A primary objective of this study is to determine the possible size of the effect that zonisamide administration has on drinking (i.e. drinks consumed per day) to allow us to plan for a larger clinical trial of the effects of zonisamide on alcohol dependence.


Condition Intervention Phase
Alcoholism
Drug: Zonisamide
Phase 2

Study Type: Interventional
Study Design: Allocation: Non-Randomized
Intervention Model: Single Group Assignment
Masking: Open Label
Primary Purpose: Treatment
Official Title: The Effects of Zonisamide on Alcohol Dependence

Resource links provided by NLM:


Further study details as provided by Boston University:

Primary Outcome Measures:
  • The Weekly Mean Number of Standard Drinks Consumed Per Day at Baseline and Treatment Phase [ Time Frame: Baseline and Week 12 ] [ Designated as safety issue: No ]
    The mean daily standard alcoholic drinks were determined for the baseline period and each treatment week as a measure of alcohol intake. One standard drink=14g of alcohol. Mean value is the difference between mean standard drinks for the baseline period and week 12 of the study.

  • Difference in Mean Words for the Phonetic Portion of the Controlled Word Association Test (COWAT). [ Time Frame: Week 0- Baseline and Week 12 ] [ Designated as safety issue: Yes ]
    Subjects were asked to generate as many words as possible starting with a particular letter over a 60 second period. Three letters were used for each sessions. Values shown are the differences between values obtained for the baseline and week 12 test session.


Secondary Outcome Measures:
  • Symbol Digit Modalities Test (DSMT) [ Time Frame: Baseline, Week 12 ] [ Designated as safety issue: Yes ]
    Number of correct digit substitutions on the DSMT per session with the possible maximum score being 188. The value shown is for difference between mean scores obtained for baseline and week 12 sessions.


Enrollment: 16
Study Start Date: November 2006
Study Completion Date: November 2009
Primary Completion Date: August 2008 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: Zonisamide
In open-label non-placebo controlled trial subjects are treatment with zonisamide 400 mg during the maintenance phase of this study
Drug: Zonisamide
Week 1 (Wk1) -100 mg daily; Wk 2- 100 mg daily; Wk 3- 200 mg daily; Wk 4- 200 mg daily; Wk 5- 300 mg daily; Wk 6- 300 mg daily; Wk 7-11- 400 mg daily; Wk 12(Days 1-5) 300 mg daily; Wk 12 (Day 6-7) Week 13 (Days 1-3)- 200 mg daily; Week 13 (Days 4-7) - 100 mg daily.

  Eligibility

Ages Eligible for Study:   21 Years to 64 Years
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

INCLUSION CRITERIA

To be admitted into this study patients must meet the following criteria:

  1. DSM IV TR Diagnosis of Alcohol Dependence; minimal level of 14 drinks per week for women or 21 drinks per week for men over a 28 day consecutive period during the 90 day period prior to the screening session.
  2. Male or Female 21-64 years of age.
  3. Able to provide informed consent and comprehend study procedures.
  4. Negative urine toxicological screen for opioids, psychomotor stimulants, sedative-hypnotics, and cannabinoids. If the urine tox screen was positive for any substance it may be repeated within two weeks.
  5. Score of >8 on the Alcohol Use Disorder Identification Test (AUDIT) during screening.
  6. Must be suitable for outpatient management of alcoholism.
  7. Express desire to stop drinking or reduce alcohol consumption with a possible long-term goal of abstinence.
  8. Provide contact information for themselves or an alternate contact that the staff will call in case of missed appointment.
  9. Women must be postmenopausal for at least one year, be surgically sterile, be using an effective method of birth control (e.g. contraceptive injection, intrauterine device, spermicide with barrier, contraceptive patch, contraceptive ring, male partner sterilization, oral contraceptives) or completely abstinent (and agree to use one of the above mentioned methods of contraception if sexual activity is ever initiated).
  10. Must be able to take oral medications, adhere to the regimen and be willing to return for follow up visits.
  11. Must have breath alcohol concentration of no more than 0.01% when the informed consent is provided and the consent form is signed.
  12. Must have resided at the same address for at least 3 months.

EXCLUSION CRITERIA

Patients meeting the following criteria will be excluded from the study:

  1. Dependent on or extensive abuse of drugs or substances other than ethanol, nicotine, or caffeine.
  2. DSM IV-TR diagnosis of any current Axis I diagnosis other than alcohol dependence, nicotine dependence, or caffeine dependence that in the opinion of the study physicians might require intervention with either pharmacological or non-pharmacological therapy that will interfere with the course of the study.
  3. Receiving inpatient or outpatient treatment for alcohol dependence (with the exception of AA or other self-help groups) within 4 weeks prior to enrollment into this study.
  4. Subjects with a score of 10 or greater on the CIWA-Ar (a withdrawal scale) on first or second visits.
  5. Currently being treated with acamprosate, disulfiram or naltrexone.
  6. Currently being treated with any of the following medications: a) Antipsychotic agents- including clozapine, risperidone, quetiapine, haloperidol b) Antimanic or anticonvulsant agents- including lithium carbonate, phenytoin, phenobarbital, carbamazepine, topiramate, valproic acid, divalproex, tiagabine c) Sedative-hypnotic or antianxiety agents-including triazolam, temazepam, zolpidem, zalepron, buspirone, alprazolam, diazepam, clonazepam, oxazepam, lorazepam d) chronic opioid treatment- including methadone, buprenorphine, oxycodone, morphine e) Psychomotor stimulants- amphetamine derivatives, methylphenidate
  7. Subjects who are legally mandated to participate in an alcohol treatment program
  8. Use of any medication known to inhibit or induce cytochrome P450 3A4 enzymes including macrolide antibiotics, fluoxetine, and carbamazepine.
  9. Subjects who have attempted suicide or who have had suicidal ideation within 30 days of their first visit as assessed using responses from the SCID and Hamilton Depression scale.
  10. Subjects with renal disease (including severe infection and cancer), impaired renal clearance (CrCl less than 50 ml/min), or history of kidney stones.
  11. Subjects with AST or ALT >3 times the upper limit of the normal range during screening.
  12. History of significant neurological disorder, including a history of seizures, stroke, dementia, multiple sclerosis, Parkinson's disease, brain tumors, or encephalitis.
  13. Subjects who are pregnant (as assessed by serum HCG) or lactating.
  14. Subjects known to have clinically significant medical conditions. These may include: symptomatic CAD or PVD, malignancy or history of malignancy in the last 5 years, significant pulmonary disease or endocrinological disorders.
  15. Subjects with prior hypersensitivity to zonisamide or related compounds, including sulfonamides (e.g. sulfisoxazole) carbonic anhydrase inhibitors (e.g. acetazolamide), sulfonylureas (e.g. chlorpropamide), sulfamates (e.g. topiramate), thiazide (e.g. hydrochlorothiazide), and loop diuretics (e.g. furosemide) except ethacrycrynic acid.
  16. Subjects who in the opinion of the study physicians should not be enrolled based on the precautions, warnings, and contraindications stated on the package insert for zonisamide.
  17. Impending incarceration.
  18. Score of 25 or less on the Folstein Mini-Mental examination.
  19. History of anticonvulsant-induced rash.
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT00406692

Locations
United States, Massachusetts
Boston University School of Medicine
Boston, Massachusetts, United States, 02118
Sponsors and Collaborators
Boston University
Investigators
Principal Investigator: Clifford Knapp, PhD Boston University
  More Information

No publications provided

Responsible Party: Clifford Knapp, PhD, Boston University
ClinicalTrials.gov Identifier: NCT00406692     History of Changes
Other Study ID Numbers: H-25544
Study First Received: November 30, 2006
Results First Received: February 8, 2010
Last Updated: May 6, 2010
Health Authority: United States: Institutional Review Board

Keywords provided by Boston University:
Zonisamide
Alcoholism
Alcohol

Additional relevant MeSH terms:
Alcoholism
Alcohol-Related Disorders
Chemically-Induced Disorders
Mental Disorders
Substance-Related Disorders
Zonisamide
Anticonvulsants
Antioxidants
Central Nervous System Agents
Molecular Mechanisms of Pharmacological Action
Pharmacologic Actions
Physiological Effects of Drugs
Protective Agents
Therapeutic Uses

ClinicalTrials.gov processed this record on October 23, 2014