GABRA2 and the Pharmacokinetics of Risk for Alcoholism (GPRA)

Study Overview
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Brief Summary
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This study will assess whether the presence of a particular form of a gene, GABRA2, affects the functional responses of the human brain to alcohol administration and will evaluate that relationship in the context of factors known to increase the risk for future alcoholism.

Detailed Description
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Each subject completed a total of 2 2.8 hr-long clamping sessions.Within each session, procedures differed only by the content of the infusate. In one session, 6% ethanol was infused. In the other session, only vehicle was infused, quantifying the placebo response for every subject. The order of alcohol or placebo sessions was counterbalanced; subjects were blind to which session was which; sessions were scheduled to occur approximately 2 weeks apart. Measures were collected before, and at beginning and end of infusion, and included subjective perceptions, EMG, EEG, stop-signal performance, eye movements, and auditory responses. Design allowed analysis of effect of alcohol vs placebo, initial effect of alcohol and acute tolerance to alcohol.

Official Title
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GABRA2 and the Pharmacokinetics of Risk for Alcoholism (GPRA)

Conditions
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Alcoholism

Intervention / Treatment
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* Other: Alcohol
* Other: Placebo


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: European American male and females between 21-27 years of age. Good health as determined by medical history, physical exam, and laboratory tests. Females must have a negative urine pregnancy (hCG) test at the start of each study session. People who consume 0.10 standard drinks per week (12 g-ethanol) per liter of total body water when averaged over the preceding month, or more, OR who have consumed more than 0.10 standard drinks per liter of total body water on any one occasion in the last month. Exclusion Criteria: Inability to read or comprehend eighth grade English. Inability to hear or comprehend verbal instructions, or inability or unwillingness to cooperate with the procedures required for the study. Inability to resolve 2 dots, each 2 mm in diameter with centers placed 5 mm apart on a card placed 20 inches from the bridge of the nose, or the need to wear eyeglasses to do so. Current or prior history of any serious disease, including head trauma causing loss of consciousness, cancer, CNS, cardiovascular, respiratory, gastrointestinal, hepatic, renal, endocrine, or alcohol or drug dependence, but not alcohol abuse or nicotine dependence. Positive hepatitis or HIV test at screening, provided subject consented to these tests. Current or prior history of alcohol-induced flushing reactions. Current diagnosis of Axis-I psychiatric illness. Positive result on urine drug screen obtained at the face-to-face interview. Pregnancy, as determined by urine HcG on each day of laboratory testing, or intention to become pregnant for women. Use of medications known to interact with alcohol within 2 weeks of the study.

Ages Eligible for Study
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Minimum Age: 21 Years
Maximum Age: 27 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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Accepts Healthy Volunteers

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Other
Intervention Model: Single Group Assignment
Interventional Model Description: Two session, within subjects, single blind
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Responses to alcohol<br>Each subject completed a total of 2 2.8 hr-long clamping sessions.Within each session, procedures differed only by the content of the infusate. In one session, 6% ethanol was infused. In the other session, only vehicle was infused, quantifying the placebo response for every subject. The order of alcohol or placebo sessions was counterbalanced; subjects were blind to which session was which; sessions were scheduled to occur about 2 weeks apart. Measures were collected before, and at beginning and end of infusion, and included subjective perceptions, EMG, EEG, stop-signal performance, eye movements, and auditory responses. Design allowed analysis of effect of alcohol vs placebo, initial effect of alcohol and acute tolerance to alcohol. | Other: Alcohol<br>* Alcohol (6% in saline vehicle) infused for 2.8 hour long clamping session (Breath alcohol level maintained at 60 mg/dL throughout).<br>Other: Placebo<br>* Placebo (saline vehicle) infused for 2.8 hour long session.<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Effect of GABRA2 SNP status on AUD risk | Results will assess the effect of GABRA2 SNPs on responses to alcohol and traits related to alcoholism risk | Both session responses and lifetime traits will be included in analysis | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Acute tolerance to alcohol | Comparison of measures taken during the initial hour of the clamp with the same measures taken during the 3rd hour of the alcohol clamp. | Within 3 hour session | 
| Initial response to alcohol | Comparison of measures taken during baseline with the same measures taken during the initial hour of the alcohol clamp. | Within 3 hour session | 
| Responses to alcohol vs placebo | Measures taken during the alcohol session will either be compared to those taken during placebo, or in some cases measures taken during the alcohol session will be corrected for placebo effects by subtracting placebo responses from alcohol responses | Within 3 hour session |