Alcohol Self Administration Laboratory
This is a pilot study in which our intent is to establish an alcohol administration laboratory in which we will be able to test the effect of the anticonvulsant medication zonisamide as compared to placebo on alcohol self administration and on cognitive functioning in non treatment seeking heavy users of alcohol. Our first goal is to establish the safety of zonisamide when used together with alcohol. Our second goal is to test the effect of an acute dose of zonisamide on alcohol consumption and show that it may reduce the consumption of alcohol. To achieve this goal we seek subjects with a history of heavy drinking to be tested on the self-administration procedures described below in two sessions with either zonisamide or placebo. These procedures will involve first, the administration of a challenge dose of ethanol to evaluate the effect of alcohol on performance on neuropsychological tests. This initial challenge will be followed by a period of alcohol self-administration in which the research subject can choose to select either ethanol or another reinforcer, money.
|Study Design:||Allocation: Non-Randomized
Endpoint Classification: Safety/Efficacy Study
Intervention Model: Crossover Assignment
Masking: Double Blind (Subject, Investigator)
|Official Title:||Alcohol Self Administration Laboratory|
- Grams Ethanol Consumed During Second Hour of the Alcohol Self-Administration Sessions [ Time Frame: 1 day ] [ Designated as safety issue: No ]Grams Ethanol Consumed During Second Hour of the Alcohol Self-Administration Sessions for Zonisamide and Placebo Conditions
- Score Digit Symbol Modalities Test [ Time Frame: 40 minutes post alcohol ingestion ] [ Designated as safety issue: Yes ]Difference score between zonisamide and placebo treatment conditions for the Digit Symbol Modalities Test scores obtained 40 minutes after ingestion of a priming dose of ethanol.This test involves transcribing form a key in which numbers appear below a series of symbols to boxes below symbols matched to those in the key. This task must be completed in 90 nseconds. This test measures visuomotor speed and aspects of attention. Scoring is the total number of correctly transcribed numbers. The maximum score on this test 110 points.
|Study Start Date:||November 2006|
|Study Completion Date:||March 2009|
|Primary Completion Date:||October 2007 (Final data collection date for primary outcome measure)|
zonisamide (100 mg)one time
Other Name: zonegran
|Placebo Comparator: Placebo||
In preclinical studies three novel anticonvulsants have been studied. The administration of tiagabine did not decrease ethanol consumption in rodents (Schmitt et al., 2002; Rimondini et al., 2002). In a study with alcohol preferring mice topiramate reduced alcohol consumption in a two bottle choice prolonged access model of drinking (Gabriel and Cunningham, 2005). In a study done at our laboratory both topiramate and zonisamide were found to have similar effects on reducing the consumption of ethanol in Wistar rat (Knapp et al., 2004). More recently we found that zonisamide administration decreased alcohol consumption in a limited access model in the C57BL/B6 mouse. These results suggest that zonisamide might be useful as a medication for the treatment of alcohol dependence.
Topiramate and zonisamide have some structural similarities with a sulfamate or methane-sulfonamide containing chain respectively attached to cyclic structure. These structural similarities may explain some of their pharmacological similarities including blockade of voltage sensitive sodium channels and low potency inhibition of carbonic anhydrase (Taverna et al., 1999; Dodgson et al., 2000; Schaf et al., 1987; Masudaet al., 1993). Both topiramate and zonisamide promote weight loss (McElroy et al., 2003; McElroy et al., 2004; Gadde et al., 2003). This effect may be a result of neuromodulation of the regulation of alcohol and food shared by these drugs.
Please refer to this study by its ClinicalTrials.gov identifier: NCT00398918
|United States, Massachusetts|
|Boston University Medical Campus|
|Boston, Massachusetts, United States, 02118|
|Principal Investigator:||Ofra Sarid-Segal, MD||Boston University|