Clinical trial NCT00681655: GABRA2 and the Pharmacokinetics of Risk for Alcoholism (GPRA)
Official title: GABRA2 and the Pharmacokinetics of Risk for Alcoholism (GPRA)
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: NA
Conditions: Alcoholism
Lead sponsor: Indiana University
Sponsor class: OTHER
Collaborators: name: National Institute on Alcohol Abuse and Alcoholism (NIAAA)
First posted: 2008-05-21
Enrollment: 141
Sex: ALL
Minimum age (years): 21
Maximum age (years): 27
Standard ages: ADULT
Accepts healthy volunteers: yes
Allocation: NA
Intervention model: SINGLE_GROUP
Intervention model description: Two session, within subjects, single blind
Primary purpose: OTHER

Brief summary: 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: 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.

Eligibility criteria: 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.

Primary outcomes:
measure: Effect of GABRA2 SNP status on AUD risk
timeFrame: Both session responses and lifetime traits will be included in analysis
Secondary outcomes:
measure: Acute tolerance to alcohol
timeFrame: Within 3 hour session
measure: Initial response to alcohol
timeFrame: Within 3 hour session
measure: Responses to alcohol vs placebo
timeFrame: Within 3 hour session
Other outcomes:
Locations:
city: Indianapolis
country: United States
facility: University Hospital
state: Indiana
Study officials:
affiliation: Indiana University School of Medicine
name: Martin H Plawecki, M.D.
role: STUDY_DIRECTOR
affiliation: Indiana University School of Medicine
name: Sean J. O'Connor, M.D.
role: PRINCIPAL_INVESTIGATOR
References:
citation: Kosobud AE, Wetherill L, Plawecki MH, Kareken DA, Liang T, Nurnberger JL, Windisch K, Xuei X, Edenberg HJ, Foroud TM, O'Connor SJ. Adaptation of Subjective Responses to Alcohol is Affected by an Interaction of GABRA2 Genotype and Recent Drinking. Alcohol Clin Exp Res. 2015 Jul;39(7):1148-57. doi: 10.1111/acer.12749. Epub 2015 Jun 19.
citation: Plawecki MH, Windisch KA, Wetherill L, Kosobud AEK, Dzemidzic M, Kareken DA, O'Connor SJ. Alcohol affects the P3 component of an adaptive stop signal task ERP. Alcohol. 2018 Aug;70:1-10. doi: 10.1016/j.alcohol.2017.08.012. Epub 2017 Aug 31.