Pharmacogenetics of Alcohol: Treatment Implications

NCT ID: NCT00734656

Last Updated: 2012-03-28

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: NA
• Total Enrollment: 94 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2007-03-31
• Study Completion Date: 2011-07-31

Brief 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

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: FACTORIAL
• Blinding Strategy: QUADRUPLE

Study Groups

Placebo medication + placebo alcohol

Group Type: PLACEBO_COMPARATOR

placebo medication + placebo alcohol

Intervention Type: DRUG

placebo medication administered 2-4 days prior to ingestion of three drinks each containing 1 cc ethanol consumed over 36 minutes

Placebo Medication + 0.8 gr/kg Ethanol

Group Type: EXPERIMENTAL

placebo medication + ethanol

Intervention Type: DRUG

placebo medication administered 2-4 days prior to ingestion of 0.8 gr/kg ethanol divided between three drinks consumed over 36 minutes

4 mg Dutasteride + Placebo Alcohol

Group Type: EXPERIMENTAL

dutasteride + placebo alcohol

Intervention Type: DRUG

4 mg dutasteride administered 2-4 days prior to ingestion of three drinks each containing 1 cc ethanol consumed over 36 minutes

4 mg Dutasteride + 0.8 gr/kg Ethanol

Group Type: EXPERIMENTAL

dutasteride + ethanol

Intervention Type: DRUG

4 mg dutasteride administered 2-4 days prior to ingestion of 0.8 mg/kg ethanol divided between three drinks consumed over 36 minutes

Interventions

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

Intervention Type: 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

Intervention Type: 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

Intervention Type: 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

Intervention Type: DRUG

Other Intervention Names

Avodart; Avodart

Eligibility Criteria

Inclusion Criteria

• Main Study: Subjects will be healthy volunteers with or without parental history of alcoholism who are 21-45 years old and who have a BMI >18.5 and <32.5. Drinking history: All subjects must report at least one occasion in the prior month of drinking at least 3 drinks on a single day; additionally, LD subjects will be selected if they drink 1-3 drinks, 1-3 times per week (up to 5 drinks per week on average), with no more than one occasion in the past 2 months on which they drank >4 drinks. HD subjects will be selected if they report drinking at least 10 drinks per week, with at least one episode per week of heavy drinking.

Exclusion Criteria

• Main Study: Subjects cannot have a current or past DSM-IV diagnosis of alcohol or drug dependence, current or past 24-months diagnosis of alcohol or drug abuse or another major psychiatric disorder, neurological illness, have had a hypersensitivity reaction to dutasteride, evidence of liver dysfunction, currently be using benzodiazepines, other psychotropic medications or medications that are known to influence steroid hormone levels or metabolism or modify the effects of alcohol. Nicotine-dependent subjects will be excluded to avoid the confounding effects of nicotine withdrawal during day-long laboratory sessions. Women are not allowed to participate. Subjects anticipating moving from the area during the period of their planned study participation will be excluded from study entry.

• Minimum Eligible Age: 21 Years
• Maximum Eligible Age: 45 Years
• Eligible Sex: MALE
• Accepts Healthy Volunteers: Yes

Sponsors

National Institutes of Health (NIH)

NIH

Sponsor Role: collaborator

National Institute on Alcohol Abuse and Alcoholism (NIAAA)

NIH

Sponsor Role: collaborator

UConn Health

OTHER

Sponsor Role: lead

Responsible Party

Jonathan Covault

Associate Professor

Responsibility Role: PRINCIPAL_INVESTIGATOR

Principal Investigators

Jonathan Covault, MD, PhD

Role: PRINCIPAL_INVESTIGATOR

UConn Health

Locations

University of Connecticut Health Center

Farmington, Connecticut, United States

Countries

United States

Other Identifiers

619

Identifier Type: OTHER_GRANT

Identifier Source: secondary_id

5R01AA015606-02

Identifier Type: NIH

Identifier Source: secondary_id

View Link

06-218S-2

Identifier Type: -

Identifier Source: org_study_id