Interdisciplinary Study of Two Novel Anticonvulsants in Alcoholism

This study is ongoing, but not recruiting participants.
Sponsor:
Collaborator:
Information provided by (Responsible Party):
Dominic Ciraulo, Boston Medical Center
ClinicalTrials.gov Identifier:
NCT00862563
First received: March 16, 2009
Last updated: November 14, 2013
Last verified: November 2013
  Purpose

This is a double-blind, placebo-controlled, parallel group design study with 4 treatment groups; levetiracetam, zonisamide, topiramate, and placebo control. Subjects will receive study medications for 14 weeks. Potential subjects will be initially screened for interest in study participation and alcohol consumption level to determine basic eligibility by telephone, or in person. Individuals who meet telephone screening criteria will be scheduled for a clinic appointment to obtain informed consent and conduct screening assessments. Subjects who report average drinks per day that are within the guidelines for safe levels of alcohol consumption (i.e. 2 drinks/ day males; 1 drink/day females-HHS standard) in the two weeks prior to screening will be excluded. Subjects meeting screening criteria will be scheduled for a second randomization visit. During this visit baseline assessments will be obtained. Eligible subjects will then be randomized to a treatment group and will be provided with the first week's study medications. The goal is to directly compare the efficacy and tolerability of two novel anticonvulsants, zonisamide and levetiracetam, with placebo, and using topiramate, which has extensive evidence supporting its efficacy in alcoholism, as a positive control group. We believe that this will be the first direct comparison of these agents in alcoholism, and the results will provide information on the efficacy and safety of the medications.


Condition Intervention Phase
Alcoholism
Alcohol Dependence
Alcohol Abuse
Drug: topiramate
Drug: zonisamide
Drug: Levetiracetam
Drug: Placebo
Phase 2

Study Type: Interventional
Study Design: Allocation: Randomized
Endpoint Classification: Safety/Efficacy Study
Intervention Model: Parallel Assignment
Masking: Double Blind (Subject, Investigator)
Primary Purpose: Treatment
Official Title: A Double-Blind, Placebo-Controlled, Parallel Group Design Trial of; Levetiracetam, Zonisamide, Topiramate, and Placebo Control for the Treatment of Alcohol Dependent Subjects.

Resource links provided by NLM:


Further study details as provided by Boston Medical Center:

Primary Outcome Measures:
  • The primary efficacy measure is the mean number of drinks consumed per day over the period from treatment weeks 10 through 12 when all study medications should be at their maximum steady levels based on their known pharmacokinetic properties. [ Time Frame: Weeks 10 through 12 ] [ Designated as safety issue: No ]

Secondary Outcome Measures:
  • the secondary outcome measure is to address neurobehavioral toxicity, the mean levels of attention and verbal fluency and a composite measure of neurotoxicity will be compared between groups. [ Time Frame: 21 weeks ] [ Designated as safety issue: Yes ]

Estimated Enrollment: 160
Study Start Date: May 2009
Estimated Study Completion Date: March 2015
Estimated Primary Completion Date: March 2014 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: Zonisamide Drug: zonisamide
Zonisamide will be administered orally twice daily beginning on Day 1, Week 1 and continue through Day 7, Week 14. Subjects will be dose titrated as tolerated to a target doses of 2000 400 mg of zonisamide.
Other Name: zonegran
Experimental: levetiracetam Drug: Levetiracetam
Levetiracetam will be administered orally twice daily beginning on Day 1, Week 1 and continue through Day 7, Week 14. Subjects will be dose titrated as tolerated to a target doses of 2000 mg levetiracetam capsules.
Other Name: Keppra
Active Comparator: topiramate Drug: topiramate
Topiramate will be administered orally twice daily beginning on Day 1, Week 1 and continue through Day 7, Week 14. Subjects will be dose titrated as tolerated to a target doses 300 mg topiramate.
Other Name: topamax
Placebo Comparator: Sugar Pill Drug: Placebo
Matched placebo will be administered orally twice daily beginning on Day 1, Week 1 and continue through Day 7, Week 14.
Other Names:
  • Placebo
  • Sugar Pill

  Eligibility

Ages Eligible for Study:   21 Years to 65 Years
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

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

  1. DSM-IV-TR Diagnosis of Alcohol Dependence.
  2. A minimal level of an average of 28 standard drinks per week for women or 35 drinks per week for men over a baseline 28 day consecutive period prior to the screening session during the 90 day time line follow-back.
  3. Male or Female 21- 65 years of age.
  4. Able to provide informed consent and comprehend study procedures.
  5. Negative urine toxicological screen for opioids, cocaine, amphetamines, methamphetamine, and benzodiazepines. The test may be repeated for opioids or benzodiazepines shown to be medically prescribed for an acute disorder. The urine test may also be repeated if the Investigator deems necessary.
  6. A score of >8 on the Alcohol Use Disorder Identification Test (AUDIT) during screening.
  7. Must be suitable for outpatient management of alcoholism.
  8. Express desire to stop drinking or reduce alcohol consumption.
  9. Provide contact information for themselves or an alternate contact that the staff will call in case of missed appointment.
  10. Women must be postmenopausal for at least one year, be surgically sterile, or be using an effective method of birth control.
  11. Must be able to take oral medications, adhere to the regimen and be willing to return for follow up visits.

Exclusion Criteria:

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

  1. Dependent on DSM IV-TR 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 treatment for alcohol dependence, other then alcohol detoxification, within 4 weeks prior to enrollment into this study.
  4. Subjects with a score of 10 or greater on the Clinical Institute Withdrawal Assessment for Alcohol-Revised on first or second visits.
  5. Being treated with acamprosate, disulfiram or naltrexone within two weeks prior to randomization:
  6. Currently being treated with any of the following medications: a) antipsychotic agents. b) antimanic or anticonvulsant agents. c) sedative- hypnotics. d) chronic opioid treatment. 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.
  9. Subjects who have attempted suicide or who have had suicidal ideation within 30 days of their first visit.
  10. Subjects with renal disease 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.
  13. Subjects who are pregnant (as assessed by serum HCG) or lactating.
  14. Subjects known to have clinically significant medical conditions that in the opinion of the study physician would preclude administration of the study medications or limit participation in the clinical trial.
  15. Subjects with history of treatment with levetiracetam, topiramate or zonisamide.
  16. Score of 25 or less on the Folstein Mini- Mental examination.
  17. History of anticonvulsant-induced rash.
  18. Taking drugs that contain "sulfa" moiety, such as sulfonamides, sulfonylureas, carbonic anhydrase inhibitors, thiazides, and loop diuretics (except ethacrynic acid).
  19. During the 2 weeks prior to screening subjects who report average drinks per day that are within the guidelines for safe levels of alcohol consumption (i.e. 2 drinks/ day males; 1 drink/day females-HHS standard) will be excluded.
  20. Subjects with a sulfa allergy.

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  Contacts and Locations
Please refer to this study by its ClinicalTrials.gov identifier: NCT00862563

Locations
United States, Massachusetts
Boston University School of Medicine
Boston, Massachusetts, United States, 02118
Sponsors and Collaborators
Boston Medical Center
Investigators
Principal Investigator: Domenic A Ciraulo, MD Boston University
  More Information

No publications provided

Responsible Party: Dominic Ciraulo, Department Chair, Psychiatry, Boston Medical Center
ClinicalTrials.gov Identifier: NCT00862563     History of Changes
Other Study ID Numbers: NIAAA-CIR-AA015923, P60AA013759, NIH Grant 1R01AA015923
Study First Received: March 16, 2009
Last Updated: November 14, 2013
Health Authority: United States: Federal Government

Keywords provided by Boston Medical Center:
Alcoholism
Alcohol Dependence
Alcohol Abuse
Substance Abuse
Alcoholic Intoxication

Additional relevant MeSH terms:
Alcoholism
Alcohol-Related Disorders
Substance-Related Disorders
Mental Disorders
Etiracetam
Topiramate
Zonisamide
Anticonvulsants
Piracetam
Central Nervous System Agents
Therapeutic Uses
Pharmacologic Actions
Nootropic Agents
Neuroprotective Agents
Protective Agents
Physiological Effects of Drugs
Anti-Obesity Agents
Antioxidants
Molecular Mechanisms of Pharmacological Action

ClinicalTrials.gov processed this record on April 17, 2014