Endophenotype for Alcohol Misuse in Healthy Minority Populations

Study Overview
=================
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.

Official Title
-----------------
Defining an Endophenotype for Alcohol Misuse: A Focus On Minority Populations

Conditions
-----------------
Healthy

Intervention / Treatment
-----------------
* Drug: Naltrexone
* Drug: placebo
* Other: alcohol
* Other: Sham alcohol


Participation Criteria
=================
Eligibility Criteria
-----------------
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.

Ages Eligible for Study
-----------------
Minimum Age: 21 Years

Sexes Eligible for Study
-----------------
All

Accepts Healthy Volunteers
-----------------
Accepts Healthy Volunteers

Study Plan
=================
How is the study designed?
-----------------

Design Details

Primary Purpose: Diagnostic
Allocation: Randomized
Intervention Model: Crossover Assignment
Masking: Quadruple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: ALC and NAL<br>alcohol and active naltrexone | Drug: Naltrexone<br>* 50 mg/day for two days prior to the alcohol challenge session<br>* Other names: ReVia;Other: alcohol<br>* 190 proof alcohol prepared to 11% volume mixed with fruit juice.<br>|
| Active Comparator: Sham ALC and NAL<br>sham alcohol and active naltrexone | Drug: Naltrexone<br>* 50 mg/day for two days prior to the alcohol challenge session<br>* Other names: ReVia;Other: Sham alcohol<br>* non-alcoholic placebo alcohol<br>|
| Placebo Comparator: placebo pill and ALC<br>placebo naltrexone and alcohol | Drug: placebo<br>* placebo pills<br>Other: alcohol<br>* 190 proof alcohol prepared to 11% volume mixed with fruit juice.<br>|
| Placebo Comparator: placebo pill and Sham ALC<br>placebo naltrexone and placebo (non-alcoholic) alcohol | Drug: placebo<br>* placebo pills<br>Other: Sham alcohol<br>* non-alcoholic placebo alcohol<br>|

What is the study measuring?
-----------------
Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Biphasic Alcohol Effects Scale - Stimulation | 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. | During challenge sessions | 
| Profile of Mood States - Vigor | 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 | during the challenge session | 
| Subjective High From Alcohol Scale | 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 | during the alcohol ingestion | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Biphasic Alcohol Effects Scale - Sedation | 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 | During the challenge session | 
| Profile of Mood States - Fatigue Scale | 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 | During the challenge session | 

 Terms related to the study
=================
Keywords Provided by Centre Hospitalier Valida
-----------------
Alcohol, Naltrexone