Healthy
Conditions
Keywords
Naltrexone, 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.
Interventions
DRUGNaltrexone
50 mg/day for two days prior to the alcohol challenge session
DRUGplacebo
placebo pills
OTHERalcohol
190 proof alcohol prepared to 11% volume mixed with fruit juice.
OTHERSham alcohol
non-alcoholic placebo alcohol
Sponsors
University of Pennsylvania
Study design
Allocation
RANDOMIZED
Intervention model
CROSSOVER
Primary purpose
DIAGNOSTIC
Masking
QUADRUPLE (Subject, Caregiver, Investigator, Outcomes Assessor)
Eligibility
Sex/Gender
ALL
Age
21 Years to No maximum
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.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| 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. |
| 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 |
| 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
| Measure | Time frame | Description |
|---|---|---|
| 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 |
| 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 |
Countries
United States
Participant flow
Pre-assignment details
Participants were only randomized to 4 sequences and not to all 12 possible sequences.
Participants by arm
| Arm | Count |
|---|---|
| Overall Study Population all participants in the cross over study | 43 |
| Total | 43 |
Baseline characteristics
| Characteristic | Overall Study Population |
|---|---|
| Age, Continuous | 35.5 years STANDARD_DEVIATION 12.9 |
| Alcohol use | 3.2 total number of drinks in the week prior STANDARD_DEVIATION 4.9 |
| Race (NIH/OMB) American Indian or Alaska Native | 0 Participants |
| Race (NIH/OMB) Asian | 0 Participants |
| Race (NIH/OMB) Black or African American | 43 Participants |
| Race (NIH/OMB) More than one race | 0 Participants |
| Race (NIH/OMB) Native Hawaiian or Other Pacific Islander | 0 Participants |
| Race (NIH/OMB) Unknown or Not Reported | 0 Participants |
| Race (NIH/OMB) White | 0 Participants |
| Sex: Female, Male Female | 23 Participants |
| Sex: Female, Male Male | 20 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk | EG002 affected / at risk | EG003 affected / at risk |
|---|---|---|---|---|
| deaths Total, all-cause mortality | 0 / 40 | 0 / 38 | 0 / 39 | 0 / 38 |
| other Total, other adverse events | 0 / 40 | 0 / 38 | 0 / 39 | 0 / 38 |
| serious Total, serious adverse events | 0 / 40 | 0 / 38 | 0 / 39 | 0 / 38 |
Outcome results
Primary
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.
Time frame: During challenge sessions
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| ALC and NAL | Biphasic Alcohol Effects Scale - Stimulation | 11.3 units on a scale | Standard Deviation 10.1 |
| Placebo ALC and NAL | Biphasic Alcohol Effects Scale - Stimulation | 3.9 units on a scale | Standard Deviation 5.1 |
| Placebo Pill and ALC | Biphasic Alcohol Effects Scale - Stimulation | 8.7 units on a scale | Standard Deviation 7.6 |
| Placebo Pill and Placebo ALC | Biphasic Alcohol Effects Scale - Stimulation | 3.2 units on a scale | Standard Deviation 4.6 |
Primary
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
Time frame: during the challenge session
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| ALC and NAL | Profile of Mood States - Vigor | 2.1 units on a scale | Standard Deviation 2.5 |
| Placebo ALC and NAL | Profile of Mood States - Vigor | 1.1 units on a scale | Standard Deviation 1.2 |
| Placebo Pill and ALC | Profile of Mood States - Vigor | 1.8 units on a scale | Standard Deviation 1.4 |
| Placebo Pill and Placebo ALC | Profile of Mood States - Vigor | 1.2 units on a scale | Standard Deviation 1.3 |
Primary
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
Time frame: during the alcohol ingestion
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| ALC and NAL | Subjective High From Alcohol Scale | 17.9 units on a scale | Standard Deviation 17.2 |
| Placebo ALC and NAL | Subjective High From Alcohol Scale | 4.5 units on a scale | Standard Deviation 5.4 |
| Placebo Pill and ALC | Subjective High From Alcohol Scale | 14.7 units on a scale | Standard Deviation 13.1 |
| Placebo Pill and Placebo ALC | Subjective High From Alcohol Scale | 2.7 units on a scale | Standard Deviation 5.3 |
Secondary
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
Time frame: During the challenge session
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| ALC and NAL | Biphasic Alcohol Effects Scale - Sedation | 14.8 units on a scale | Standard Deviation 13.7 |
| Placebo ALC and NAL | Biphasic Alcohol Effects Scale - Sedation | 13.4 units on a scale | Standard Deviation 16.1 |
| Placebo Pill and ALC | Biphasic Alcohol Effects Scale - Sedation | 15.9 units on a scale | Standard Deviation 15.8 |
| Placebo Pill and Placebo ALC | Biphasic Alcohol Effects Scale - Sedation | 15.4 units on a scale | Standard Deviation 16.3 |
Secondary
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
Time frame: During the challenge session
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| ALC and NAL | Profile of Mood States - Fatigue Scale | 2.2 units on a scale | Standard Deviation 2.1 |
| Placebo ALC and NAL | Profile of Mood States - Fatigue Scale | 1.6 units on a scale | Standard Deviation 1.4 |
| Placebo Pill and ALC | Profile of Mood States - Fatigue Scale | 2.0 units on a scale | Standard Deviation 1.6 |
| Placebo Pill and Placebo ALC | Profile of Mood States - Fatigue Scale | 1.5 units on a scale | Standard Deviation 1.4 |