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AlcoholismPhase 2NCT00862563

Interdisciplinary Study of Two Novel Anticonvulsants in Alcoholism

A Phase 2 study testing Topiramate, Zonisamide and Levetiracetam in people with Alcoholism and Alcohol Dependence, run by Boston Medical Center at 1 site in United States.

Terminated

Stopped early. The study ended before it was planned to and will not resume.

Official record
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Trial 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. Read more about this study

Who is it for?
Ages 21 to 65 years
Conditions the study is for
Alcoholism, Alcohol Dependence, Alcohol Abuse
What is being tested?
Topiramate, Zonisamide and Levetiracetam
Type of treatment
Pill or oral medicine
Could I receive a placebo?
Yes, some participants may receive a placebo
How many people
85 participants
Where
1 siteUnited States
Study dates
May 2009to Aug 2013
Phase
Phase 2
Are there results?
Yes, posted in the registrySummary in the doctors' view

Key requirements

Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.

  • Ages 21 to 65 years
  • All sexes
  • No healthy volunteers
  • Adult, Older adult

Who may be able to join

  • 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.
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  • 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.

Who cannot join

  • 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:
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  • 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.
  • Subjects with history of treatment with levetiracetam, topiramate or zonisamide.
  • Score of 25 or less on the Folstein Mini- Mental examination.
  • History of anticonvulsant-induced rash.
  • Taking drugs that contain "sulfa" moiety, such as sulfonamides, sulfonylureas, carbonic anhydrase inhibitors, thiazides, and loop diuretics (except ethacrynic acid).
  • 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.
  • Subjects with a sulfa allergy.
  • -

Trial locations and contacts

1 site in 1 country.

United States1 site
  • Boston University School of Medicine

    Boston, Massachusetts, 02118

Other trials in United States

About this study

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.

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.

Read the detailed description

This is a double-blind, placebo-controlled, parallel group design study with 4 treatment groups; levetiracetam, zonisamide, topiramate, and placebo control. This study evaluated the effects of zonisamide (400 mg per day) on alcohol consumption and its neurotoxic effects in subjects with AUDS. A double-blind placebo-controlled clinical trial was conducted using two comparator anticonvulsant drugs, topiramate (300 mg daily) and levetiracetam (2000 mg/day), which does not impair cognition. Topiramate was used as an active control in this study.

Study medications were administered for 14 weeks, including a 2-week taper period. Target maintenance doses of study medications were administered to subjects during study weeks 8-12. Dosage reductions were made if needed to allow subjects to tolerate their study medication. During the medication taper phase of the study (Weeks 13-14) the Principal Investigator is allowed flexibility in the titration schedule in instances when the subject is experiencing events consistent with withdrawal, for example anxiety. Neurotoxicity of study drugs was assessed using neuropsychological tests and the AB-Neurotoxicity scale.

An adaptive randomization procedures with sex and heavy drinking history being factors in the assignment of subjects to the treatment groups. will be done using sex and very heavy drinking. Very heavy drinking is defined as male subjects consuming more then 10 standard drinks per day and female subjects consuming more then 8 standard drinks per day for more then 40 percent of the days in the screening TLFB.

Medication adherence was facilitated using Brief Behavioral Compliance Enhancement Treatment. It is a brief, standardized therapy that emphasizes medication adherence as being crucial to the improvement of drinking behavior.

Subject assessments included, but were not limited to the following:

  1. TLFB, 2) Adverse Events (AEs) assessment ,3) A-B Neurotoxicity Scale (weeks 1,4,8,12,15),and 4) Neuropsychological battery Assessments- including the Controlled Word Association Test (COWAT) and Digit and Spatial Span portions of the Wechsler Memory Scale- 3rd (weeks 1,12).
Being tested
Topiramate, Zonisamide, Levetiracetam, Sugar Pill
Keywords
Alcoholism, Alcohol Dependence, Alcohol Abuse, Substance Abuse, Alcoholic Intoxication
Medical subject headings
Alcoholism, Substance-Related Disorders, Alcoholic Intoxication

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

  • TopiramateDrug

    Also called Topamax

    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.

  • ZonisamideDrug

    Also called zonegran

    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.

  • LevetiracetamDrug

    Also called Keppra

    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.

  • Sugar PillDrug

    Also called Placebo

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

Study groups in NCT00862563
Study groupRoleWhat they receive
ZonisamideExperimentalEncapsulated zonisamide with a target maintenance doses of 400 mg/day administered as 4 capsules per day.
Receives: Drug: Zonisamide
LevetiracetamExperimentalEncapsulated levetiracetam with a target maintenance doses of 2000 mg/day administered as 4 capsules per day .
Receives: Drug: Levetiracetam
TopiramateActive comparatorEncapsulated topiramate with a target maintenance doses of 300 mg/day administered as 4 capsules per day .
Receives: Drug: Topiramate
Sugar PillPlacebo comparatorEncapsulated sugar pill with a target maintenance dose administered as 4 capsules per day.
Receives: Drug: Sugar Pill

What is being measured

The primary outcome is the main question the study is designed to answer.

  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.

    Measured: Weeks 10, 11, 12

Secondary outcomes (7)
  1. AB-Neurotoxicity Scale.

    Total Scores AB-Neurotoxicity Scale Week 12. This scale provides subject ratings of anticonvulsant neurotoxic effects. Scores may range 0 to 72, with possibility of an additional 30 points being for complaints not listed in the list of complaints provides. Total scores, therefore, may be as high as 102, with higher scores indicating greater severity of problems. Actual mean scores are shown. Means for the analysis are least means squares values obtained from a two-way repeated measures mixed models analysis, with Week (time) as the the within subject factor and treatment as the between group factor. Baseline values were used as covariates.

    Measured: Week 12

  2. Mean Percent Days Heavy Drinking

    Mean weekly values for each treatment group for percent days heavy drinking. Heavy drinking was defined as 4 or more drinks per day for women and 5 or more drinks per day for men.

    Measured: Weeks 10, 11, 12

  3. Percent Days Drinking

    Mean percent days drinking for Weeks 10, 11, 12. A drinking day is considered to be a day in which 1 or more drinks have been consumed. Means are model generated least means squares values obtained from a two-way repeated measures analysis from data obtained from Weeks 1 through 12, with Week as the within subject factor and treatment group as the between group factor.

    Measured: Weeks 10, 11, 12

  4. Controlled Word Association Test (COWAT)- Letter Fluency

    Number of words generated that start with a set of 3 letters. The COWAT provides a measure of verbal fluency. Actual means for COWAT results are shown.

    Measured: Baseline & Week 12

  5. COWAT-Category

    Number of words produced by subjects over 60 seconds for a semantic category (Animals). The COAWAT-Category sub-test provides a measure of verbal fluency. Mean value shown are actual means for the number of words produced.

    Measured: Baseline, Week12

  6. Wechsler Memory Scales (WMS)-3d Ed Digit Span-Age Adjusted Total

    WMS Digit Span is a measure of working memory. Subjects respond by repeating lists of number sequences presented by the test administrator. Age adjusted scores are presented below. Scores may range between 1 and 19, with lower scores indicating poorer performance on the task.

    Measured: Baseline, Week 12

  7. Wechsler Memory Scale-3rd Ed. Spatial Span

    WMS Spatial Span test measures working memory for a spatial sequence of numbers. This assesses visual working memory. Age adjusted scaled scores are presented. Score may range between 1 and 19, with lower scores indicating greater impairment in performance.

    Measured: Baseline, Week 12

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

  1. First posted17 Mar 2009 (estimated)
  2. Study startMay 2009
  3. Primary completionAug 2013
  4. Study completionAug 2013

Why it stopped: Recruitment goals could not be met before ending of funding for this project.

Resources

More details

For doctors and researchers: how the study is designed, who runs it, and its registry IDs.

Study design
Study type
Interventional
Phase
Phase 2
Primary purpose
Treatment
Allocation
Randomised
Intervention model
Parallel groups
Masking
Double blind
Who is masked
Participant, Investigator
Enrolment
85 participants (actual)
IDs, dates and publications
ClinicalTrials.gov ID
NCT00862563
Sponsor's protocol ID
NIAAA-CIR-AA015923
Other IDs
P60AA013759, 1R01AA015923
Status last verified
Apr 2015
First submitted
16 Mar 2009
Last updated
28 Apr 2015
Data monitoring committee
Yes

Publications

  • 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.

    PubMed 25427171

Questions about this trial

What is this clinical trial studying?

A Phase 2 study testing Topiramate, Zonisamide and Levetiracetam in people with Alcoholism and Alcohol Dependence, run by Boston Medical Center at 1 site in United States.

The full registered description is in the About this study section and the official record.

Who may be eligible to take part?

The sponsor lists 12 inclusion and 22 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.

Is this clinical trial currently recruiting?

The record says: stopped early, as of the sponsor's last update on 28 Apr 2015. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 1 site in United States. Whether a site is taking part right now should be confirmed with that site. See every site.

What are the possible benefits and risks?

They depend on the study and the treatment, and no study can promise a benefit. Some participants in this study may receive a placebo. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.

What does this phase mean?

Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.

Not every study follows the same path, and some studies (observational studies, device studies) have no phase.

Are results available for this study?

Yes. Results are posted in the registry (first posted 7 Apr 2015). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.

How can a doctor refer a patient or contact the research team?

The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.

What does the primary outcome measure?

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, 11, 12). It is what the study was designed to measure, not a finding.

Where can I read the original study information?

On the ClinicalTrials.gov record for NCT00862563, which also lists 1 linked publication.

Does a listing mean the treatment is approved or proven to work?

No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.

How often is this information updated?

AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 28 Apr 2015.

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