GABA Mechanisms Underlying the Vulnerability to Alcohol Dependence
|Study Design:||Allocation: Randomized
Endpoint Classification: Pharmacodynamics Study
Intervention Model: Crossover Assignment
Masking: Double Blind (Subject, Outcomes Assessor)
Primary Purpose: Health Services Research
|Official Title:||GABA Mechanisms Underlying the Vulnerability to Alcohol Dependence|
- Biphasic Alcohol Effects Scale, confirmed with other measures such as the Visual Analog Scales [ Time Frame: Baseline, +10, +20, +80, +110, +170, +230 ] [ Designated as safety issue: Yes ]
- potential response P300 measurements, grooved pegboard test [ Time Frame: Baseline and during infusion ] [ Designated as safety issue: Yes ]
|Study Start Date:||November 2005|
|Study Completion Date:||April 2012|
|Primary Completion Date:||April 2012 (Final data collection date for primary outcome measure)|
Active Comparator: Thiopental
thiopental 1.5mg/kg (loading) with a subsequent infusion rate of 40 mcg/kg/minute (60 minute infusion).
A 2-day test design involving 2 conditions: saline or thiopental 1.5mg/kg (loading) with a subsequent infusion rate of 40 mcg/kg/minute (60 minute infusion).
Placebo Comparator: Placebo
saline (60 minute infusion).
This project will explore the hypothesis that individuals with a family history positive for alcohol dependence (FHP) (without any current DSM-IV Axis I disorder, except nicotine dependence), experience an alteration in the reward "valence" (balance of positive and negative effects) of the GABA-A receptor agonist barbiturate (thiopental) compared to family history negative (FHN) age-matched subjects. Further, the effect of variations in genes important in regulating brain GABA function may alter a component of the discriminative stimulus effects of ethanol. FHP individuals are defined as individuals with at least one first-degree relative and another first- or second-degree relatives. Preliminary results suggest that FHP individuals showed an attenuated response to thiopental as measured by the descending limb of the BAES during thiopental infusion relative to the FHN group. Further, preliminary results suggest that variation in genes involved in brain GABA function, glutamate decarboxylase-65 (GAD65), may influence the risk for alcoholism by altering a component of the discriminative stimulus effects of ethanol.
We plan to recruit 2 groups of healthy subjects between the ages of 21-30, one with a family history of alcoholism (family history positive=FHP) and a sex-matched control group without a family history of alcoholism (family history negative=FHN), to undergo two test days scheduled 3 days apart, in a randomized double-blind fashion. Test days will involve a 60-minute intravenous infusion of each of 2 conditions: saline or thiopental, in a randomized order under double-blind conditions. Behavioral ratings include the Biphasic Alcohol Effects Scale (BAES) and Visual Analog Scales (VAS). Exploratory measures include event-related potential recordings (ERP) and measures of eye-to-hand coordination. Blood will be collected for Deoxyribonucleic acid (DNA) extraction and genotyping.
Please refer to this study by its ClinicalTrials.gov identifier: NCT00611767
|United States, Connecticut|
|VA Connecticut Healthcare System|
|West Haven, Connecticut, United States, 06516|
|Principal Investigator:||Ismene L Petrakis, MD||Yale University|