DEFINE: Endophenotype for Alcohol Misuse in Healthy Minority Populations

• Sponsor: University of Pennsylvania (Other)
• Overall Status: Completed
• CT.gov ID: NCT00256451
• Collaborator: (none)
• Enrollment: 43
• Location: 1
• Arms: 4
• Duration (Months): 30
• Patients Per Site Per Month: 1.4

Study Details

Study Description

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.

Condition or Disease	Intervention/Treatment	Phase
Healthy	Drug: Naltrexone; Drug: placebo; Other: alcohol; Other: Sham alcohol	Phase 4

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 Design

• Study Type: Interventional
• Actual Enrollment: 43 participants
• Allocation: Randomized
• Intervention Model: Crossover Assignment
• Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
• Primary Purpose: Diagnostic
• Official Title: Defining an Endophenotype for Alcohol Misuse: A Focus On Minority Populations
• Study Start Date: Nov 1, 2005
• Actual Primary Completion Date: May 1, 2008
• Actual Study Completion Date: May 1, 2008

Arms and Interventions

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

Outcome Measures

Primary Outcome Measures

1. 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.

2. 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

3. 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

1. 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

2. 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

Eligibility Criteria

Criteria

• Ages Eligible for Study: 21 Years and Older
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: Yes

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.

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	University of Pennsylvania Treatment Research Center	Philadelphia	Pennsylvania	United States	19104

Sponsors and Collaborators

• University of Pennsylvania

Investigators

• Principal Investigator: David Oslin, MD, University of Pennsylvania

Study Documents (Full-Text)

None provided.

More Information

Publications

None provided.

• Responsible Party: David Oslin, Principal Investigator, University of Pennsylvania
• ClinicalTrials.gov Identifier: NCT00256451
• Other Study ID Numbers: 803866
• First Posted: Nov 21, 2005
• Last Update Posted: Aug 21, 2019
• Last Verified: Aug 1, 2019

• Individual Participant Data (IPD) Sharing Statement: No
• Plan to Share IPD: No
• Keywords provided by David Oslin, Principal Investigator, University of Pennsylvania: Naltrexone; Alcohol
• Additional relevant MeSH terms: Ethanol; Naltrexone

Study Results

Participant Flow

Pre-assignment Detail	Participants were only randomized to 4 sequences and not to all 12 possible sequences.

Arm/Group Title	Ntx-Alc; Placebo-Sham; Ntx-Sham; Placebo-Alc	Ntx-Sham; Ntx-Alc; Placebo-Alc; Placebo-Sham	Placebo-Alc; Ntx-Sham; Placebo-Sham; Ntx-Alc	Placebo-Sham; Placebo-Alc; Ntx-Alc; Ntx-Sham
Arm/Group Description	Session1: alcohol and active naltrexone Naltrexone: 50 mg/day for two days prior to the alcohol challenge session alcohol: 190 proof alcohol prepared to 11% volume mixed with fruit juice. Session2:placebo naltrexone and placebo (non-alcoholic) alcohol placebo: placebo pills Sham alcohol: non-alcoholic placebo alcohol Session3: "sham" alcohol and active naltrexone Naltrexone: 50 mg/day for two days prior to the alcohol challenge session Sham alcohol: non-alcoholic placebo alcohol Session4: placebo naltrexone and alcohol placebo: placebo pills alcohol: 190 proof alcohol prepared to 11% volume mixed with fruit juice.	Session1: "sham" alcohol and active naltrexone Naltrexone: 50 mg/day for two days prior to the alcohol challenge session Sham alcohol: non-alcoholic placebo alcohol Session2: alcohol and active naltrexone Naltrexone: 50 mg/day for two days prior to the alcohol challenge session alcohol: 190 proof alcohol prepared to 11% volume mixed with fruit juice. Session3: placebo naltrexone and alcohol placebo: placebo pills alcohol: 190 proof alcohol prepared to 11% volume mixed with fruit juice. Session4: placebo naltrexone and placebo (non-alcoholic) alcohol placebo: placebo pills Sham alcohol: non-alcoholic placebo alcohol	Session1: placebo naltrexone and alcohol placebo: placebo pills alcohol: 190 proof alcohol prepared to 11% volume mixed with fruit juice. Session2: "sham" alcohol and active naltrexone Naltrexone: 50 mg/day for two days prior to the alcohol challenge session Sham alcohol: non-alcoholic placebo alcohol Session3:placebo naltrexone and placebo (non-alcoholic) alcohol placebo: placebo pills Sham alcohol: non-alcoholic placebo alcohol Session4: alcohol and active naltrexone Naltrexone: 50 mg/day for two days prior to the alcohol challenge session alcohol: 190 proof alcohol prepared to 11% volume mixed with fruit juice.	Session1: placebo naltrexone and placebo (non-alcoholic) alcohol placebo: placebo pills Sham alcohol: non-alcoholic placebo alcohol Session2: placebo naltrexone and alcohol placebo: placebo pills alcohol: 190 proof alcohol prepared to 11% volume mixed with fruit juice. Session3: alcohol and active naltrexone Naltrexone: 50 mg/day for two days prior to the alcohol challenge session alcohol: 190 proof alcohol prepared to 11% volume mixed with fruit juice. Session4: "sham" alcohol and active naltrexone Naltrexone: 50 mg/day for two days prior to the alcohol challenge session Sham alcohol: non-alcoholic placebo alcohol
Period Title: Session1
STARTED	10	11	11	11
COMPLETED	10	11	11	11
NOT COMPLETED	0	0	0	0
Period Title: Session1
STARTED	9	11	10	10
COMPLETED	9	11	10	10
NOT COMPLETED	0	0	0	0
Period Title: Session1
STARTED	9	9	10	9
COMPLETED	9	9	10	9
NOT COMPLETED	0	0	0	0
Period Title: Session1
STARTED	9	8	10	8
COMPLETED	9	8	10	8
NOT COMPLETED	0	0	0	0

Baseline Characteristics

Arm/Group Title	Overall Study Population
Arm/Group Description	all participants in the cross over study
Overall Participants	43
Age (years) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [years]	35.5 (12.9)
Sex: Female, Male (Count of Participants)
Female	23 53.5%
Male	20 46.5%
Race (NIH/OMB) (Count of Participants)
American Indian or Alaska Native	0 0%
Asian	0 0%
Native Hawaiian or Other Pacific Islander	0 0%
Black or African American	43 100%
White	0 0%
More than one race	0 0%
Unknown or Not Reported	0 0%
Alcohol use (total number of drinks in the week prior) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [total number of drinks in the week prior]	3.2 (4.9)

Outcome Measures

1. Primary Outcome

Title	Biphasic Alcohol Effects Scale - Stimulation
Description	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.
Time Frame	During challenge sessions

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	ALC and NAL	Placebo ALC and NAL	Placebo Pill and ALC	Placebo Pill and Placebo ALC
Arm/Group Description	alcohol and active naltrexone Naltrexone: 50 mg/day for two days prior to the alcohol challenge session alcohol: 190 proof alcohol prepared to 11% volume mixed with fruit juice.	"sham" alcohol and active naltrexone Naltrexone: 50 mg/day for two days prior to the alcohol challenge session Sham alcohol: non-alcoholic placebo alcohol	placebo naltrexone and alcohol placebo: placebo pills alcohol: 190 proof alcohol prepared to 11% volume mixed with fruit juice.	placebo naltrexone and placebo (non-alcoholic) alcohol placebo: placebo pills Sham alcohol: non-alcoholic placebo alcohol
Measure Participants	40	38	39	38
Mean (Standard Deviation) [units on a scale]	11.3 (10.1)	3.9 (5.1)	8.7 (7.6)	3.2 (4.6)

2. Primary Outcome

Title	Profile of Mood States - Vigor
Description	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
Time Frame	during the challenge session

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	ALC and NAL	Placebo ALC and NAL	Placebo Pill and ALC	Placebo Pill and Placebo ALC
Arm/Group Description	alcohol and active naltrexone Naltrexone: 50 mg/day for two days prior to the alcohol challenge session alcohol: 190 proof alcohol prepared to 11% volume mixed with fruit juice.	"sham" alcohol and active naltrexone Naltrexone: 50 mg/day for two days prior to the alcohol challenge session Sham alcohol: non-alcoholic placebo alcohol	placebo naltrexone and alcohol placebo: placebo pills alcohol: 190 proof alcohol prepared to 11% volume mixed with fruit juice.	placebo naltrexone and placebo (non-alcoholic) alcohol placebo: placebo pills Sham alcohol: non-alcoholic placebo alcohol
Measure Participants	40	38	39	38
Mean (Standard Deviation) [units on a scale]	2.1 (2.5)	1.1 (1.2)	1.8 (1.4)	1.2 (1.3)

3. Primary Outcome

Title	Subjective High From Alcohol Scale
Description	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
Time Frame	during the alcohol ingestion

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	ALC and NAL	Placebo ALC and NAL	Placebo Pill and ALC	Placebo Pill and Placebo ALC
Arm/Group Description	alcohol and active naltrexone Naltrexone: 50 mg/day for two days prior to the alcohol challenge session alcohol: 190 proof alcohol prepared to 11% volume mixed with fruit juice.	"sham" alcohol and active naltrexone Naltrexone: 50 mg/day for two days prior to the alcohol challenge session Sham alcohol: non-alcoholic placebo alcohol	placebo naltrexone and alcohol placebo: placebo pills alcohol: 190 proof alcohol prepared to 11% volume mixed with fruit juice.	placebo naltrexone and placebo (non-alcoholic) alcohol placebo: placebo pills Sham alcohol: non-alcoholic placebo alcohol
Measure Participants	40	38	39	38
Mean (Standard Deviation) [units on a scale]	17.9 (17.2)	4.5 (5.4)	14.7 (13.1)	2.7 (5.3)

4. Secondary Outcome

Title	Biphasic Alcohol Effects Scale - Sedation
Description	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
Time Frame	During the challenge session

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	ALC and NAL	Placebo ALC and NAL	Placebo Pill and ALC	Placebo Pill and Placebo ALC
Arm/Group Description	alcohol and active naltrexone Naltrexone: 50 mg/day for two days prior to the alcohol challenge session alcohol: 190 proof alcohol prepared to 11% volume mixed with fruit juice.	"sham" alcohol and active naltrexone Naltrexone: 50 mg/day for two days prior to the alcohol challenge session Sham alcohol: non-alcoholic placebo alcohol	placebo naltrexone and alcohol placebo: placebo pills alcohol: 190 proof alcohol prepared to 11% volume mixed with fruit juice.	placebo naltrexone and placebo (non-alcoholic) alcohol placebo: placebo pills Sham alcohol: non-alcoholic placebo alcohol
Measure Participants	40	38	39	38
Mean (Standard Deviation) [units on a scale]	14.8 (13.7)	13.4 (16.1)	15.9 (15.8)	15.4 (16.3)

5. Secondary Outcome

Title	Profile of Mood States - Fatigue Scale
Description	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
Time Frame	During the challenge session

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	ALC and NAL	Placebo ALC and NAL	Placebo Pill and ALC	Placebo Pill and Placebo ALC
Arm/Group Description	alcohol and active naltrexone Naltrexone: 50 mg/day for two days prior to the alcohol challenge session alcohol: 190 proof alcohol prepared to 11% volume mixed with fruit juice.	"sham" alcohol and active naltrexone Naltrexone: 50 mg/day for two days prior to the alcohol challenge session Sham alcohol: non-alcoholic placebo alcohol	placebo naltrexone and alcohol placebo: placebo pills alcohol: 190 proof alcohol prepared to 11% volume mixed with fruit juice.	placebo naltrexone and placebo (non-alcoholic) alcohol placebo: placebo pills Sham alcohol: non-alcoholic placebo alcohol
Measure Participants	40	38	39	38
Mean (Standard Deviation) [units on a scale]	2.2 (2.1)	1.6 (1.4)	2.0 (1.6)	1.5 (1.4)

Adverse Events

Time Frame	Adverse events were monitored during each session which typically occurred over 3 hours.
Adverse Event Reporting Description	We assessed for any adverse event reported related to the medication taken prior to the session or the alcohol during the session.
Arm/Group Title	ALC and NAL		Placebo ALC and NAL		Placebo Pill and ALC		Placebo Pill and Placebo ALC
Arm/Group Description	alcohol and active naltrexone Naltrexone: 50 mg/day for two days prior to the alcohol challenge session alcohol: 190 proof alcohol prepared to 11% volume mixed with fruit juice.		"sham" alcohol and active naltrexone Naltrexone: 50 mg/day for two days prior to the alcohol challenge session Sham alcohol: non-alcoholic placebo alcohol		placebo naltrexone and alcohol placebo: placebo pills alcohol: 190 proof alcohol prepared to 11% volume mixed with fruit juice.		placebo naltrexone and placebo (non-alcoholic) alcohol placebo: placebo pills Sham alcohol: non-alcoholic placebo alcohol
All Cause Mortality
	ALC and NAL		Placebo ALC and NAL		Placebo Pill and ALC		Placebo Pill and Placebo ALC
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	0/40 (0%)		0/38 (0%)		0/39 (0%)		0/38 (0%)
Serious Adverse Events
	ALC and NAL		Placebo ALC and NAL		Placebo Pill and ALC		Placebo Pill and Placebo ALC
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	0/40 (0%)		0/38 (0%)		0/39 (0%)		0/38 (0%)
Other (Not Including Serious) Adverse Events
	ALC and NAL		Placebo ALC and NAL		Placebo Pill and ALC		Placebo Pill and Placebo ALC
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	0/40 (0%)		0/38 (0%)		0/39 (0%)		0/38 (0%)

Limitations/Caveats

[Not Specified]

More Information

Certain Agreements

Principal Investigators are NOT employed by the organization sponsoring the study.

There is NOT an agreement between Principal Investigators and the Sponsor (or its agents) that restricts the PI's rights to discuss or publish trial results after the trial is completed.