The Effects of Levetiracetam on Alcohol Dependent Subjects
|Study Design:||Allocation: Non-Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
|Official Title:||The Effects of Levetiracetam on Alcohol Dependent Subjects|
- Change in mean number of drinks [ Time Frame: Baseline and at 11 weeks ]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.
- Heavy drinks per drinking day [ Time Frame: At 13 weeks and last value carries forward approaches ]Mean heavy drinks per drinking day, OCDS scores, MOS-Sleep Scores, and POMS scores.
- OCDS scores, MOS-Sleep Scores, and POMS scores. [ Time Frame: At 13 weeks and last value carries forward approaches ]Mean OCDS scores, MOS-Sleep Scores, and POMS scores.
|Actual Study Start Date:||January 2006|
|Study Completion Date:||October 2009|
|Primary Completion Date:||January 2007 (Final data collection date for primary outcome measure)|
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
Other Name: Keppra
Placebo Comparator: Historical controls
Historical controls from COMBINE study who receive a placebo
|Other: Historical controls|
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.
Please refer to this study by its ClinicalTrials.gov identifier: NCT00325182
|United States, Massachusetts|
|Boston University Dept of Psychiatry Clinical Studies Unit|
|Boston, Massachusetts, United States, 02118|
|Principal Investigator:||Ofra Sarid-Segal, MD||Boston University|