Endophenotype for Alcohol Misuse in Healthy Minority Populations (DEFINE)

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

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.

Study Overview

• Status: Completed
• Conditions: Healthy
• Intervention / Treatment: Drug: placebo; Drug: Naltrexone; Other: alcohol; Other: Sham alcohol

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.

• Study Type: Interventional
• Enrollment (Actual): 43
• Phase: Phase 4

Contacts and Locations

Study Locations

• United States
  • Pennsylvania
    • Philadelphia, Pennsylvania, United States, 19104
      • University of Pennsylvania Treatment Research Center

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 21 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: Yes
• Genders Eligible for Study: All

Description

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.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Diagnostic
• Allocation: Randomized
• Interventional Model: Crossover Assignment
• Masking: Quadruple

Number of Arms

4

Arms and Interventions

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

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

Collaborators and Investigators

• Sponsor: University of Pennsylvania

Study record dates

Study Major Dates

• Study Start: November 1, 2005
• Primary Completion (Actual): May 1, 2008
• Study Completion (Actual): May 1, 2008

Study Registration Dates

• First Submitted: November 17, 2005
• First Submitted That Met QC Criteria: November 17, 2005
• First Posted (Estimate): November 21, 2005

Study Record Updates

• Last Update Posted (Actual): August 21, 2019
• Last Update Submitted That Met QC Criteria: August 16, 2019
• Last Verified: August 1, 2019

More Information

Terms related to this study

• Keywords: Alcohol; Naltrexone
• Additional Relevant MeSH Terms: Physiological Effects of Drugs; Anti-Infective Agents, Local; Anti-Infective Agents; Central Nervous System Depressants; Peripheral Nervous System Agents; Sensory System Agents; Narcotic Antagonists; Alcohol Deterrents; Ethanol; Naltrexone
• Other Study ID Numbers: 803866

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO