NCT00734656

Pharmacogenetics of Alcohol: Treatment Implications

Subjective and Physiological Effects of Alcohol: Role of Genetic Variation and Adrenal Hormones

• Status: Completed
• Phase: N/A
• Study type: Interventional
• Enrollment: 94 (actual)
• Sponsor: UConn Health · Academic / Other
• Sex: Male
• Age: 21 Years – 45 Years
• Healthy volunteers: Accepted

Summary

This study will explore the hypothesis that effects of alcohol are in part mediated by increased production of neuroactive steroids, which interact with GABAA-receptors. We propose to study non-dependent drinkers using a 4-session within-subjects design in which alcohol / placebo is paired with dutasteride / placebo pretreatment. Dutasteride is a 5-alpha steroid reductase (5AR) inhibitor that limits the production of dihydrotestosterone and the 5a-reduced neuroactive steroids allopregnanolone, pregnanolone and 3a,5a-androstanediol.

Detailed description

Alcohol has multiple pharmacological effects, though which of these effects relate to the risk of alcohol dependence is not clear. Animal studies indicate that the neuroactive steroid allopregnanolone is an alcohol-modulated endogenous agonist at GABAA receptors and that genetic variation in steroid 5a-reductase type I gene which generates neuroactive steroids, may moderate alcohol effects. To better define the role of neuroactive steroids we will conduct a laboratory study of non-alcohol dependent drinkers using a 4-session design in which alcohol/placebo beverage is paired with dutasteride/placebo pretreatment. Dutasteride, an inhibitor of both type I and type II 5a-reductase enzymes, blocks the production of 5a-reduced neuroactive steroids. This study will extend our preliminary findings with finasteride by including a) a placebo control for alcohol, b) a more specific inhibitor of both 5a-reductase isoenzymes, c) a larger group of subjects (including both light and heavy drinkers).

Conditions

• Alcohol Related Disorders
• Alcoholism
• Alcohol Abuse

Interventions

Type	Name	Description
DRUG	dutasteride + ethanol	4 mg dutasteride administered 2-4 days prior to ingestion of 0.8 mg/kg ethanol divided between three drinks consumed over 36 minutes
DRUG	placebo medication + ethanol	placebo medication administered 2-4 days prior to ingestion of 0.8 gr/kg ethanol divided between three drinks consumed over 36 minutes
DRUG	dutasteride + placebo alcohol	4 mg dutasteride administered 2-4 days prior to ingestion of three drinks each containing 1 cc ethanol consumed over 36 minutes
DRUG	placebo medication + placebo alcohol	placebo medication administered 2-4 days prior to ingestion of three drinks each containing 1 cc ethanol consumed over 36 minutes

Timeline

• Start date: 2007-03-01
• Primary completion: 2010-10-01
• Completion: 2011-07-01
• First posted: 2008-08-14
• Last updated: 2012-03-28
• Results posted: 2012-03-27

Locations

1 site across 1 country: United States