Endophenotype for Alcohol Misuse in Healthy Minority Populations

Phase 4

Completed

Interventions: Drug: placebo
Drug: Naltrexone
Other: alcohol
Other: Sham alcohol

Brief Summary: The purpose of the study is to understand the relationship between what an individual inherited from their family (genetics), how they respond and feel after drinking alcohol, and how they respond to pre-treatment with naltrexone, a medication that blocks some of the effects of alcohol and is approved for the treatment of alcoholism. The investigators are conducting this study on those of African descent because there is almost no research focused on this group and the association with genetics. The investigators seek to enroll 40 people in the study. Participation will consist of 4 different alcohol challenge sessions in a cross over design. Each session will be separated by at least 10 days. In total, there will be four challenge sessions.

Detailed Description: We propose to test the degree to which specific genetic markers alter the relationship between subjective and objective measures of response to alcohol ingestion among non-alcohol dependent adults of African descent in a laboratory environment. To meet this aim, non-alcohol dependent adults of African descent will be recruited for participation to meet the N-goal of 40 trial completers. After consenting, genotyping, and completing the baseline assessment, they will participate in four separate alcohol challenge sessions separated by at least 10 days. During each of the sessions, subjects will be administered alcohol or sham drinking challenge sessions and pretreatment with either naltrexone (50 mg/day) or placebo in a double-blind fashion. The order of the four sessions will be randomly assigned. During each session, physiological and subjective response will be measured. We will select subjects to assure equal number of participants with at least one copy of the Val6 allele compared to those homozygous for the Ala6 allele.

Recruitment & Eligibility

Inclusion Criteria

Male or female and 21 years of age or older
Drinks less than an average of 21 drinks/week with no more than 2 binge episodes per week
Of African descent by self report

Exclusion Criteria

Meets DSM-IV criteria for lifetime dependence on any substance other than nicotine
Subjects who test positive on the urine drug screen for opioids, cocaine, marijuana, or amphetamine at the screening visit
Subjects who meet current or lifetime DSM-IV criteria for bipolar affective disorder, schizophrenia, or any psychotic disorder
The presence of unstable or serious medical illness; including history of stroke, seizure disorder, severe liver disease (AST or ALT > 5X normal at the time of randomization), or unstable cardiac disease
Needs treatment with any psychotropic medication (antidepressant, antipsychotic, benzodiazepine, or mood stabilizing medication)
Pre-menopausal female subjects who are pregnant, nursing, or not using a reliable method of contraception
Insulin-dependent diabetes
Any medical or psychological condition that could jeopardize the subject's safe participation in the trial as determined by the PI.

Arm && Interventions

Group	Intervention	Description
placebo pill and ALC	placebo	placebo naltrexone and alcohol
placebo pill and ALC	alcohol	placebo naltrexone and alcohol
ALC and NAL	alcohol	alcohol and active naltrexone
placebo pill and Sham ALC	Sham alcohol	placebo naltrexone and placebo (non-alcoholic) alcohol
Sham ALC and NAL	Sham alcohol	"sham" alcohol and active naltrexone
placebo pill and Sham ALC	placebo	placebo naltrexone and placebo (non-alcoholic) alcohol
ALC and NAL	Naltrexone	alcohol and active naltrexone
Sham ALC and NAL	Naltrexone	"sham" alcohol and active naltrexone

Primary Outcome Measures

Name	Time	Method
Profile of Mood States - Vigor	during the challenge session	Change from baseline to peak for the amount of Vigor experienced after alcohol ingestion Profile of Mood States - Vigor: sum of 6 items each rated on 5 point Likert scale (0: not at all, 4: extremely). Minimum=0, maximum=20, higher scores = better outcome
Biphasic Alcohol Effects Scale - Stimulation	During challenge sessions	Change from baseline to peak for the feeling of stimulation after alcohol ingestion Biphasic Alcohol Effects Scale - Stimulation: sum of 7 items each rated on 11 point Likert scale (0=not at all, 10=extremely). Minimum=0, maximum=70, higher scores=worse outcome.
Subjective High From Alcohol Scale	during the alcohol ingestion	Change from baseline to peak for the self reported feeling of being high after drinking Subjective High from Alcohol Scale: sum of 15 items rated on a 8 point Likert scale (0-7). Minimum=0, maximum=105, higher scores=worse outcomes

Secondary Outcome Measures

Name	Time	Method
Profile of Mood States - Fatigue Scale	During the challenge session	Change from baseline to peak of the degree of fatigue experienced after alcohol ingestion Profile of Mood States - Fatigue scale: sum of 5 items rated on 5-point Likert scale (0=not at all, 4=extremely). Minimum=0, maximum=20, higher score=worse outcome
Biphasic Alcohol Effects Scale - Sedation	During the challenge session	Change from baseline to peak of the amount of sedation post ingestion of alcohol Biphasic alcohol effects scale - Sedation: sum of 7 items rated on 11 point Likert scale (0=not at all, 10=extremely). Minimum=0, maximum=70, lower scores=worse outcomes