The Effects of Levetiracetam on Alcohol Dependent Subjects

This study will attempt to examine whether Levetiracetam (Keppra (TM)) can help people with alcohol dependence cut down on their alcohol consumption. In addition, the investigation will assess the effectiveness of Keppra on reducing withdrawal symptoms post alcohol cessation. Matched group of historical controls of alcohol dependent patients receiving placebo will be used for comparison.Based on the mechanism of action of Keppra we hypothesize that it may be effective in promoting abstinence and reducing drinking behavior in alcohol dependent patients.

Study Overview

• Status: Completed
• Conditions: Alcoholism
• Intervention / Treatment: Drug: Levetiracetam; Other: Historical controls

Detailed Description

Alcoholism is a chronic disease with numerous psychological, social and medical consequences. Alcohol use disorders are one of the most prevalent psychiatric disorders in general population in the US. Alcoholism not only disrupts an individual's life, health and ability to function in the society, has tremendous impact on families and communities, but also is associated with enormous economic cost for society. The medical and social impact of alcoholism can be reduced via effective treatments. Although medical, psychological and social approaches have demonstrated some efficacy, no specific method has consistently shown superiority. Similarly, currently available pharmacological treatments for alcohol use disorders are associated with moderate efficacy, indicating that further efforts are required to develop novel interventions.

The rewarding effects of alcohol are at least partially mediated via dopamine pathways that originate in the ventral tegmental area and project to the nucleus accumbens. Alcohol through its effects on GABA receptor activity decreases the inhibitory effect of GABA on the dopaminergic neurons in ventral tegmental area and therefore facilitates dopamine neurotransmission. Medications that modulate excitatory neurotransmission in the brain (glutamate) and facilitate inhibitory effects of GABA have been shown to be clinically effective in treatment of alcoholism.

Keppra is a novel antiepileptic medication currently approved for treatment of partial onset seizures as an adjunctive agent. It has a unique mechanism of action in that it reduces negative allosteric effects of Zn++ and Beta- carboline in two main inhibitory receptors in the CNS- the GABA A and glycine receptors. These modulators inhibit the influx of chloride though both of these receptor complexes and are therefore considered excitatory mediators. Keppra prevents the negative modulation and promotes chloride flux, thereby, inhibiting neurotransmission.

Limited laboratory work with levetiracetam (Keppra) has shown that the medication can reverse the anxiogenic effect of benzodiazepine withdrawal in mice (Y. Lamberty et al., 2002). Furthermore, Keppra was investigated for its potential to prevent alcohol withdrawal symptoms in mice. In this study levetiracetam dose-dependently prevented spontaneous tremors and handling induced convulsions in alcohol dependent mice. (Y. Lamberty et al., 2002). Based on the mechanism of action of Keppra we hypothesize that it may be effective in promoting abstinence and reducing drinking behavior in alcohol dependent patients.

• Study Type: Interventional
• Enrollment (Actual): 40
• Phase: Phase 4

Contacts and Locations

Study Locations

• United States
  • Massachusetts
    • Boston, Massachusetts, United States, 02118
      • Boston University Dept of Psychiatry Clinical Studies Unit

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 21 years to 60 years (Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

• DSM IV TR Diagnosis of Alcohol Dependence
• Male or female age 21-60 years old
• Able to provide informed consent and comprehend study procedures
• Negative urine toxicological screen for narcotics, amphetamines, sedative hypnotics and cannabinoids. The test may be repeated within a week.
• Score of > 8 on Alcohol Use Disorder Identification Test during screening
• Must be suitable for outpatient management
• Express desire to stop drinking or reduce alcohol consumption with possible long-term goal of abstinence.
• Provide contact information for themselves or an alternate contact that the study staff will contact in case of missed appointment.
• Female subjects must be postmenopausal for at least one year, or practicing an effective method of birth control before entry and throughout the study
• Must be able to take oral medications, adhere to regimen and be willing to return for follow up visits
• Must have breath alcohol concentration of no more than 0.025% when signing the informed consent

Exclusion criteria:

• Dependent on or extensive abuse of drugs or substances other than ethanol, nicotine or caffeine
• DSM IV- TR diagnosis of any current Axis I diagnosis other than alcohol, nicotine or caffeine dependence that in the investigator's judgment might require intervention with either pharmacological or non-pharmacological therapy that might interfere with the course of the study
• Receiving inpatient or outpatient treatment for alcohol dependence (with the exception of AA or other self-help groups) within the 4 weeks prior to enrollment
• Subjects with a score of 10 or greater on the CIWA-Ar at visits one and two
• Currently being treated with disulfiram or naltrexone
• Currently being treated with any the following medications: a) Antipsychotic agent [b) Lithium Carbonate c) Anticonvulsant agent d) Hypnotics e) Antianxiety Agents f) Chronic opiate treatment with methadone, laam, buprenorphine; oxycodone, morphine, etc g) Stimulant treatment
• Subjects who are legally mandated to participate in alcohol treatment program
• Subjects who have had a suicide attempt or suicidal ideation within 30 days of the first visit
• Subjects with renal disease
• Subjects with AST and ALT >3 times the upper limit of the normal range during screening. Test may be repeated prior to enrollment. If repeat lab values are all within acceptable ranges subject may continue study participation.
• Major neurological disorder including seizures
• Subjects who are pregnant or lactating
• Subjects known to have clinically significant medical conditions, including, but not limited to: symptomatic CAD or PVD, malignancy or history of malignancy in the last 5 years, pulmonary disorders, endocrinological disorders
• Subjects with prior hypersensitivity to Keppra
• Subjects with history of medically complicated withdrawal from alcohol.
• Subjects who in the opinion of the investigator should not be enrolled in the study because of the precautions, warnings and contraindications outlined in the Keppra package insert
• Subjects with cardiac pacemaker or metal surgical implant

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Non-Randomized
• Interventional Model: Parallel Assignment
• Masking: None (Open Label)

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Intervention: Levetiracetam; Levetiracetam dose schedule Days 1-4 250 mg bid Days 5- 19 500 mg bid Days 20 -70 1000 mg bid Days 71-78 500 mg bid Days 79-85 250 mg bid Days 86-91	Drug: Levetiracetam; Other Names: Keppra
Placebo Comparator: Historical controls; Historical controls from COMBINE study who receive a placebo	Other: Historical controls

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Change in mean number of drinks	The primary outcome of this study will be determined by comparing the mean drinks consumed per day at baseline (the month prior to the screening session) compared with the mean drinks per day consumed during week 11 of the treatment period.	Baseline and at 11 weeks

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Heavy drinks per drinking day	Mean heavy drinks per drinking day, OCDS scores, MOS-Sleep Scores, and POMS scores.	At 13 weeks and last value carries forward approaches
OCDS scores, MOS-Sleep Scores, and POMS scores.	Mean OCDS scores, MOS-Sleep Scores, and POMS scores.	At 13 weeks and last value carries forward approaches

Collaborators and Investigators

• Sponsor: Boston University
• Collaborators: UCB Pharma
• Investigators: Principal Investigator: Ofra Sarid-Segal, MD, Boston University

Study record dates

Study Major Dates

• Study Start (Actual): January 1, 2006
• Primary Completion (Actual): January 1, 2007
• Study Completion (Actual): October 1, 2009

Study Registration Dates

• First Submitted: May 11, 2006
• First Submitted That Met QC Criteria: May 11, 2006
• First Posted (Estimate): May 12, 2006

Study Record Updates

• Last Update Posted (Actual): March 15, 2017
• Last Update Submitted That Met QC Criteria: March 13, 2017
• Last Verified: April 1, 2007

More Information

Terms related to this study

• Keywords: Alcoholism
• Additional Relevant MeSH Terms: Mental Disorders; Chemically-Induced Disorders; Alcohol-Related Disorders; Substance-Related Disorders; Alcoholism; Anticonvulsants; Nootropic Agents; Levetiracetam
• Other Study ID Numbers: H-23008

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: No