Interdisciplinary Study of Two Novel Anticonvulsants in Alcoholism

NCT00862563 | Terminated Phase 2 Results DMC

• 3 other identifiers: NIAAA-CIR-AA015923P60AA0137591R01AA015923
• Study Type: interventional
• Target: 85
• Locations: 1 country
• Sites: 1

Brief Summary

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.

Conditions

Alcoholism; Alcohol Dependence; Alcohol Abuse

Keywords

Alcoholism; Alcohol Dependence; Alcohol Abuse; Substance Abuse; Alcoholic Intoxication

Outcome Measures

Primary Outcomes (1)

• 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.

  Mean standard drinks consumed per day for each treatment week, weeks 10 thru 12. Actual mean values obtained are shown. Analyses are based on model generated least squares means for a two -way repeated measures mixed models analysis for data obtained for weeks 1 through 12, with baseline values used as covariates. Week (time) was used as the within subject factor and treatment group was the between group factor.

  Weeks 10, 11, 12

Secondary Outcomes (7)

• AB-Neurotoxicity Scale.

  Week 12

• Mean Percent Days Heavy Drinking

  Weeks 10, 11, 12

• Percent Days Drinking

  Weeks 10, 11, 12

• Controlled Word Association Test (COWAT)- Letter Fluency

  Baseline & Week 12

• COWAT-Category

  Baseline, Week12

Study Arms (4)

Zonisamide

EXPERIMENTAL

Encapsulated zonisamide with a target maintenance doses of 400 mg/day administered as 4 capsules per day.

Drug: Zonisamide

Levetiracetam

EXPERIMENTAL

Encapsulated levetiracetam with a target maintenance doses of 2000 mg/day administered as 4 capsules per day .

Drug: Levetiracetam

Topiramate

ACTIVE COMPARATOR

Encapsulated topiramate with a target maintenance doses of 300 mg/day administered as 4 capsules per day .

Drug: Topiramate

Sugar Pill

PLACEBO COMPARATOR

Encapsulated sugar pill with a target maintenance dose administered as 4 capsules per day.

Drug: Sugar Pill

Interventions

Topiramate DRUG

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.

Also known as: Topamax

Topiramate

Zonisamide DRUG

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.

Also known as: zonegran

Zonisamide

Levetiracetam DRUG

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.

Also known as: Keppra

Levetiracetam

Sugar Pill DRUG

Matched placebo will be administered orally twice daily beginning on Day 1, Week 1 and continue through Day 7, Week 14.

Also known as: Placebo

Sugar Pill

Eligibility Criteria

• Age: 21 Years - 65 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• To be admitted into this study candidates must meet the following criteria:
• DSM-IV-TR Diagnosis of Alcohol Dependence.
• 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.
• Male or Female 21- 65 years of age.
• Able to provide informed consent and comprehend study procedures.
• 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.
• A score of \>8 on the Alcohol Use Disorder Identification Test (AUDIT) during screening.
• Must be suitable for outpatient management of alcoholism.
• Express desire to stop drinking or reduce alcohol consumption.
• Provide contact information for themselves or an alternate contact that the staff will call in case of missed appointment.
• Women must be postmenopausal for at least one year, be surgically sterile, or be using an effective method of birth control.
• Must be able to take oral medications, adhere to the regimen and be willing to return for follow up visits.

You may not qualify if:

• Subjects meeting the following criteria will be excluded from the study:
• Dependent on DSM IV-TR drugs or substances other than ethanol, nicotine, or caffeine.
• 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.
• Receiving inpatient treatment for alcohol dependence, other then alcohol detoxification, within 4 weeks prior to enrollment into this study.
• Subjects with a score of 10 or greater on the Clinical Institute Withdrawal Assessment for Alcohol-Revised on first or second visits.
• Being treated with acamprosate, disulfiram or naltrexone within two weeks prior to randomization:
• 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
• Subjects who are legally mandated to participate in an alcohol treatment program.
• Use of any medication known to inhibit or induce cytochrome P450 3A4 enzymes.
• Subjects who have attempted suicide or who have had suicidal ideation within 30 days of their first visit.
• Subjects with renal disease or history of kidney stones.
• Subjects with AST or ALT \>3 times the upper limit of the normal range during screening.
• History of significant neurological disorder.
• Subjects who are pregnant (as assessed by serum HCG) or lactating.
• 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.

Sponsors & Collaborators

• Boston Medical Center: lead
• National Institute on Alcohol Abuse and Alcoholism (NIAAA): collaborator

Study Sites (1)

Boston University School of Medicine

Boston, Massachusetts, 02118, United States

Location

Related Publications (1)

• Knapp CM, Ciraulo DA, Sarid-Segal O, Richardson MA, Devine E, Streeter CC, Oscar-Berman M, Surprise C, Colaneri L, Putnam M, Waters M, Richambault C. Zonisamide, topiramate, and levetiracetam: efficacy and neuropsychological effects in alcohol use disorders. J Clin Psychopharmacol. 2015 Feb;35(1):34-42. doi: 10.1097/JCP.0000000000000246.

  PMID: 25427171 DERIVED

MeSH Terms

Conditions

Alcoholism; Substance-Related Disorders; Alcoholic Intoxication

Interventions

Topiramate; Zonisamide; Levetiracetam; Sugars

Condition Hierarchy (Ancestors)

Alcohol-Related Disorders; Chemically-Induced Disorders; Mental Disorders

Intervention Hierarchy (Ancestors)

Fructose; Hexoses; Monosaccharides; Carbohydrates; Ketoses; Sulfonamides; Amides; Organic Chemicals; Sulfones; Sulfur Compounds; Isoxazoles; Azoles; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds; Acetamides; Acetates; Acids, Acyclic; Carboxylic Acids; Pyrrolidinones; Pyrrolidines

Limitations and Caveats

Early termination lead to a small number of subjects in each group being analyzed.

Results Point of Contact

• Title: Dr. Domenic A Ciraulo, Professor
• Organization: Department of Psychiatry, Boston Univ School of Medicine

dciraulo@bu.edu

617-414-1990

Study Officials

• Domenic A Ciraulo, MD

  Boston University

  PRINCIPAL INVESTIGATOR

Publication Agreements

• PI is Sponsor Employee: No
• Restrictive Agreement: No

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: DOUBLE
• Who Masked: PARTICIPANT, INVESTIGATOR
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Department Chair, Psychiatry

Study Record Dates

• First Submitted: March 16, 2009
• First Posted: March 17, 2009
• Study Start: May 1, 2009
• Primary Completion: August 1, 2013
• Study Completion: August 1, 2013
• Last Updated: April 28, 2015
• Results First Posted: April 7, 2015

Record last verified: 2015-04

Locations

US (1)