Naltrexone for Individuals of East Asian Descent

• Sponsor: University of California, Los Angeles (Other)
• Overall Status: Completed
• CT.gov ID: NCT02026011
• Collaborator: National Institute on Alcohol Abuse and Alcoholism (NIAAA) (NIH)
• Enrollment: 87
• Location: 1
• Arms: 2
• Duration (Months): 33
• Patients Per Site Per Month: 2.6

Study Details

Study Description

Brief Summary

This study will elucidate the pharmacogenetic effects of the Asn40Asp SNP of the OPRM1 gene on biobehavioral and neural markers of response to naltrexone in individuals of East Asian descent, an ethnic group most likely to express the positive predictive allele.

Condition or Disease	Intervention/Treatment	Phase
Alcohol Use Disorder	Drug: Naltrexone; Drug: Placebo	Phase 2

Detailed Description

Recent pharmacogenetic studies have advanced the gene coding for µ-opioid receptors (OPRM1) gene as a potential moderator of responses to naltrexone. The most widely studied polymorphism of the OPRM1 gene is the Asn40Asp single nucleotide polymorphism (SNP), a functional mutation thought to affect receptor activity such that the Asp40 variant binds β-endorphin three times stronger than the Asn40 allele. Recent studies have found that Asp40 carriers have a stronger striatal dopamine response to intravenous alcohol administration and report stronger feelings of alcohol reward. Findings from the COMBINE Study demonstrated that if treated with Medication Management alone and naltrexone, 87.1% of Asp40 carriers had a good clinical outcome, compared with only 54.8% of Asn40 homozygotes. While these findings are promising, studies have also highlighted allele frequency imbalance as a function of ethnicity such that the Asp40 allele frequency is approximately 20% in Caucasians, 5% in individuals of African Ancestry, and as high as 50% among individuals of East Asian descent. Therefore, to the extent to which this SNP moderates behavioral and clinical responses to NTX, ethnicity must be carefully considered in order to extend the findings from primarily Caucasian samples to ethnic minorities, such as Asian Americans. Preliminary work by our team has found that among individuals of East Asian descent, Asp40 carriers show greater NTX-induced blunting of alcohol craving as well as potentiation of the aversive effects of alcohol. This pilot study also found support for a gene dose-response, such that Asp40Asp individuals showed greater NTX responsivity than those with the Asn40Asp genotype. This study seeks to build upon these preliminary findings by testing heavy drinkers of East Asian descent across three OPRM1 genotypes (Asn40Asn, n = 30; Asn40Asp, n = 30, and Asp40Asp, n = 30). Participants will complete two double-blinded, counterbalanced alcohol infusion and self-administration sessions, one after taking NTX (50 mg/day) and one after taking matched placebo for five days. In each medication condition, participants will complete a functional neuroimaging task examining cue-induced craving for alcohol. This study will elucidate the pharmacogenetic effects of the Asn40Asp SNP of the OPRM1 gene on biobehavioral and neural markers of response to naltrexone in individuals of Asian descent, an ethnic group most likely to express the positive predictive allele (Asp40). The long-term objective of this research is to optimize alcoholism pharmacotherapy and to address health disparities by advancing pharmacogenetic studies in ethnic minority groups.

Study Design

• Study Type: Interventional
• Actual Enrollment: 87 participants
• Allocation: Randomized
• Intervention Model: Crossover Assignment
• Masking: Triple (Participant, Investigator, Outcomes Assessor)
• Primary Purpose: Treatment
• Official Title: Optimizing Naltrexone for Individuals of East Asian Descent
• Study Start Date: Dec 1, 2013
• Actual Primary Completion Date: Sep 1, 2016
• Actual Study Completion Date: Sep 1, 2016

Arms and Interventions

Arm	Intervention/Treatment
Experimental: Naltrexone Naltrexone 50 mg/day	Drug: Naltrexone; Naltrexone is an opioid receptor antagonist with highest affinity for mu opioid receptors; Other Names: Revia Depade Vivitrol
Placebo Comparator: Sugar pill Matched placebo	Drug: Placebo; Sugar pill, matched to the active study medication in capsule size and color; Other Names: Sugar pill

Outcome Measures

Primary Outcome Measures

1. Subjective Response - Craving for Alcohol [The AUQ was administered across a period of approximately 1.5 hours.]

   Alcohol Urge Questionnaire (AUQ) is used to assess subjective experiences of craving for alcohol. It consists of 8 items, each rated on a 7-point Likert scale (1 = strongly disagree, 7 = strongly agree). A summary score is used at each assessment time point. The AUQ was administered at baseline and three levels of breath alcohol concentration: 0.02 g/dl. 0.04, g/dl, and 0.06 g/dl.

2. Subjective Response - Stimulation [The BAES Stimulant Subscale was administered at baseline and three levels of breath alcohol concentration: 0.2 g/dl. 0.04, g/dl, and 0.06 g/dl taking place within approximately 1.5 hours]

   The Biphasic Alcohol Effects Scale (BAES) Stimulant Subscale consists of 14 items designed to capture the stimulant effects of alcohol, rated on an 11-point scale (0 = not at all. 10 = extremely). Total score for the stimulant subscale ranges from 0-70.

3. Subjective Response - Sedation [The BAES Sedation Subscale was administered at baseline and three levels of breath alcohol concentration: 0.2 g/dl. 0.04, g/dl, and 0.06 g/dl taking place within approximately 1.5 hours]

   The Biphasic Alcohol Effects Scale (BAES) Sedation Subscale consists of 14 items designed to capture the sedating effects of alcohol, rated on an 11-point scale (0 = not at all. 10 = extremely). Total score for the sedation subscale ranges from 0-70.

4. Neural Response to Alcohol Cues [During the alcohol cue exposure fMRI paradigm which is expected to last 45 minutes]

   Alcohol taste cues task for functional magnetic resonance imaging (fMRI). Region of Interest (ROI) were atomically defined using the Harvard-Oxford atlas in standard Montreal Neurological Institute (MNI) space, which were transformed into individual participants' native space using Functional Magnetic Resonance Imaging of the Brain Software Library (FSL). Contrast estimates are for Alc > Water cue, and are arbitrary units.

Secondary Outcome Measures

1. Alcohol Self-administration - Number of Drinks [Alcohol self-administration period was 1 hour long]

   Total number of drinks consumed during the alcohol self-administration task

Eligibility Criteria

Criteria

• Ages Eligible for Study: 21 Years to 65 Years
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: No

Inclusion Criteria:

• current (i.e., past month) alcohol dependence

• East Asian ethnicity (i.e., Chinese, Korean, or Japanese)

• Prospective genotyping for the A118G SNP of the mu opioid receptor (OPRM1) gene to allow for balanced groups on all three genotypes (AA, AG, GG)

Exclusion Criteria:

• lifetime DSM-IV of drug dependence (other than alcohol or nicotine)

• current use of psychoactive drugs as determined by self-reports and verified using toxicology testing

• lifetime diagnosis of bipolar disorder or any psychotic disorder

• contraindications to an MRI scan (including left handedness)

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	UCLA Addictions Laboratory	Los Angeles	California	United States	90095

Sponsors and Collaborators

• University of California, Los Angeles
• National Institute on Alcohol Abuse and Alcoholism (NIAAA)

Investigators

• Principal Investigator: Lara Ray, PhD, University of California, Los Angeles

Study Documents (Full-Text)

None provided.

More Information

Additional Information:

• UCLA Addictions Laboratory

Publications

• Ray LA, Bujarski S, Chin PF, Miotto K. Pharmacogenetics of naltrexone in asian americans: a randomized placebo-controlled laboratory study. Neuropsychopharmacology. 2012 Jan;37(2):445-55. doi: 10.1038/npp.2011.192. Epub 2011 Sep 7.

• Responsible Party: Lara Ray, PhD, Associate Professor, University of California, Los Angeles
• ClinicalTrials.gov Identifier: NCT02026011
• Other Study ID Numbers: NTX-AA; R01AA021744
• First Posted: Jan 1, 2014
• Last Update Posted: Jul 17, 2019
• Last Verified: Jun 1, 2019

• Individual Participant Data (IPD) Sharing Statement: No
• Plan to Share IPD: No
• Keywords provided by Lara Ray, PhD, Associate Professor, University of California, Los Angeles: alcohol use disorder; naltrexone; Asian American; pharmacogenetics; OPRM1 gene
• Additional relevant MeSH terms: Alcoholism; Alcohol Drinking; Naltrexone

Study Results

Participant Flow

Pre-assignment Detail	A total of 199 individuals were screened in the laboratory, of those 106 completed the physical exam, and of those 87 were eligible and agreed to be randomized. Participants received in random order either Naltrexone (titrated up to 50 mg/day) or Placebo at each Allocation.

Arm/Group Title	Allocated to Naltrexone	Allocated to Placebo
Arm/Group Description	Group that was randomly assigned to receive Naltrexone first.	Group that was randomly assigned to receive Placebo first
Period Title: Allocation 1 (First Set of Medication)
STARTED	46	41
COMPLETED	38	39
NOT COMPLETED	8	2
Period Title: Allocation 1 (First Set of Medication)
STARTED	38	37
COMPLETED	37	35
NOT COMPLETED	1	2

Baseline Characteristics

Arm/Group Title	Asn40Asn Genotype	Asn40asp/Asp40Asp Genotype	Total
Arm/Group Description	Group that is homozygotes for the Asn40 allele	Group that is a carrier of the Asp40 allele	Total of all reporting groups
Overall Participants	29	48	77
Age (years) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [years]	28.72 (7.57)	25.69 (4.84)	26.83 (6.15)
Sex: Female, Male (Count of Participants)
Female	9 31%	19 39.6%	28 36.4%
Male	20 69%	29 60.4%	49 63.6%
Race/Ethnicity, Customized (Count of Participants)
Chinese	12 41.4%	13 27.1%	25 32.5%
Japanese	2 6.9%	6 12.5%	8 10.4%
Korean	11 37.9%	24 50%	35 45.5%
Taiwanese	4 13.8%	5 10.4%	9 11.7%
Region of Enrollment (Count of Participants)
United States	29 100%	48 100%	77 100%
Alcohol Use Disorder Identification Test (AUDIT) (units on a scale) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [units on a scale]	16.14 (5.82)	13.17 (4.83)	14.29 (5.39)

Outcome Measures

1. Primary Outcome

Title	Subjective Response - Craving for Alcohol
Description	Alcohol Urge Questionnaire (AUQ) is used to assess subjective experiences of craving for alcohol. It consists of 8 items, each rated on a 7-point Likert scale (1 = strongly disagree, 7 = strongly agree). A summary score is used at each assessment time point. The AUQ was administered at baseline and three levels of breath alcohol concentration: 0.02 g/dl. 0.04, g/dl, and 0.06 g/dl.
Time Frame	The AUQ was administered across a period of approximately 1.5 hours.

Outcome Measure Data

Analysis Population Description

Participants who completed at least one experimental session.

Arm/Group Title	Naltrexone - Asn40Asn	Naltrexone - Asn40Asp/Asp40Asp	Placebo - Asn40Asn	Placebo - Asn40Asp/Asp40Asp
Arm/Group Description	Group that was randomized to receive Naltrexone (50 mg/d) and is homozygote for the Asn40 allele.	Group that was randomized to receive Naltrexone (50mg/d) and carries at least one copy of the Asp40 allele.	The group that was randomized to receive placebo and is homozygote for the Asn40 allele.	Group that was randomized to receive Placebo and carries at least one copy of the Asp40 allele.
Measure Participants	27	48	28	46
BrAC = 0.02 g/dl	1.7037 (0.9295)	1.9965 (1.2862)	2.1012 (1.2881)	1.8478 (0.9812)
BrAC = 0.04 g/dl	1.9198 (1.1260)	2.1319 (1.3024)	2.3095 (1.4499)	2.2645 (1.2311)
BrAc = 0.06 g/dl	2.0185 (1.3590)	2.2014 (1.3430)	2.3095 (1.4400)	2.4891 (1.4595)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Naltrexone - Asn40Asn, Naltrexone - Asn40Asp/Asp40Asp, Placebo - Asn40Asn, Placebo - Asn40Asp/Asp40Asp
	Comments
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	0.39
	Comments	Medication effect: b = -0.15, SE = 0.17, t = -0.86, p = 0.39
	Method	Mixed Models Analysis
	Comments

Statistical Analysis 2

Statistical Analysis Overview	Comparison Group Selection	Naltrexone - Asn40Asn, Naltrexone - Asn40Asp/Asp40Asp, Placebo - Asn40Asn, Placebo - Asn40Asp/Asp40Asp
	Comments
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	0.34
	Comments	Genotype effect: b = 0.20, SE = 0.21, t = 0.96, p = 0.34
	Method	Mixed Models Analysis
	Comments

Statistical Analysis 3

Statistical Analysis Overview	Comparison Group Selection	Naltrexone - Asn40Asn, Naltrexone - Asn40Asp/Asp40Asp, Placebo - Asn40Asn, Placebo - Asn40Asp/Asp40Asp
	Comments
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	0.04
	Comments	BrAC effect: b = 0.13, SE = 0.06, t = 2.10, p = 0.04
	Method	Mixed Models Analysis
	Comments

Statistical Analysis 4

Statistical Analysis Overview	Comparison Group Selection	Naltrexone - Asn40Asn, Naltrexone - Asn40Asp/Asp40Asp, Placebo - Asn40Asn, Placebo - Asn40Asp/Asp40Asp
	Comments
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	0.47
	Comments	Medication by genotype interaction: b = 0.15, SE = 0.21, t = 0.73, p = 0.47
	Method	Mixed Models Analysis
	Comments

Statistical Analysis 5

Statistical Analysis Overview	Comparison Group Selection	Naltrexone - Asn40Asn, Naltrexone - Asn40Asp/Asp40Asp, Placebo - Asn40Asn, Placebo - Asn40Asp/Asp40Asp
	Comments
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	0.13
	Comments	Medication by genotype by BrAC interaction: b = -0.20, SE = 0.13, t = -1.52, p = 0.13
	Method	Mixed Models Analysis
	Comments

2. Primary Outcome

Title	Subjective Response - Stimulation
Description	The Biphasic Alcohol Effects Scale (BAES) Stimulant Subscale consists of 14 items designed to capture the stimulant effects of alcohol, rated on an 11-point scale (0 = not at all. 10 = extremely). Total score for the stimulant subscale ranges from 0-70.
Time Frame	The BAES Stimulant Subscale was administered at baseline and three levels of breath alcohol concentration: 0.2 g/dl. 0.04, g/dl, and 0.06 g/dl taking place within approximately 1.5 hours

Outcome Measure Data

Analysis Population Description

Participants who completed at least one experimental session.

Arm/Group Title	Naltrexone - Asn40Asn	Naltrexone - Asn40Asp/Asp40Asp	Placebo - Asn40Asn	Placebo - Asn40Asp/Asp40Asp
Arm/Group Description	Group that was randomized to receive Naltrexone (50 mg/d) and is homozygote for the Asn40 allele.	Group that was randomized to receive Naltrexone (50mg/d) and carries at least one copy of the Asp40 allele.	The group that was randomized to receive placebo first and is homozygote for the Asn40 allele.	Group that was randomized to receive Placebo and carries at least one copy of the Asp40 allele.
Measure Participants	27	48	28	46
BrAC = 0.02 g/dl	2.0423 (1.7338)	2.0893 (1.8291)	2.0102 (1.9867)	1.8106 (1.7512)
BrAC = 0.04 g/dl	2.2963 (1.8860)	2.7679 (1.9415)	2.3316 (2.0949)	2.4658 (1.9971)
BrAc = 0.06 g/dl	2.8307 (2.3581)	3.0149 (2.1955)	2.2347 (1.9917)	3.0466 (2.4146)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Naltrexone - Asn40Asn, Naltrexone - Asn40Asp/Asp40Asp, Placebo - Asn40Asn, Placebo - Asn40Asp/Asp40Asp
	Comments
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	0.23
	Comments	Medication effect: b = 0.16, SE = 0.13, t = 1.20, p = 0.23
	Method	Mixed Models Analysis
	Comments

Statistical Analysis 2

Statistical Analysis Overview	Comparison Group Selection	Naltrexone - Asn40Asn, Naltrexone - Asn40Asp/Asp40Asp, Placebo - Asn40Asn, Placebo - Asn40Asp/Asp40Asp
	Comments
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	0.09
	Comments	Genotype effect: b = 0.37, SE = 0.22, t = 1.69, p = 0.09
	Method	Mixed Models Analysis
	Comments

Statistical Analysis 3

Statistical Analysis Overview	Comparison Group Selection	Naltrexone - Asn40Asn, Naltrexone - Asn40Asp/Asp40Asp, Placebo - Asn40Asn, Placebo - Asn40Asp/Asp40Asp
	Comments
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	0.84
	Comments	Medication by genotype interaction: b = 0.04, SE = 0.21, t = 0.20, p = 0.84
	Method	Mixed Models Analysis
	Comments

Statistical Analysis 4

Statistical Analysis Overview	Comparison Group Selection	Naltrexone - Asn40Asn, Naltrexone - Asn40Asp/Asp40Asp, Placebo - Asn40Asn, Placebo - Asn40Asp/Asp40Asp
	Comments
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	0.05
	Comments	Medication by genotype by BrAC interaction: b = -0.32, SE = 0.16, t = -1.93, p = 0.05
	Method	Mixed Models Analysis
	Comments

3. Primary Outcome

Title	Subjective Response - Sedation
Description	The Biphasic Alcohol Effects Scale (BAES) Sedation Subscale consists of 14 items designed to capture the sedating effects of alcohol, rated on an 11-point scale (0 = not at all. 10 = extremely). Total score for the sedation subscale ranges from 0-70.
Time Frame	The BAES Sedation Subscale was administered at baseline and three levels of breath alcohol concentration: 0.2 g/dl. 0.04, g/dl, and 0.06 g/dl taking place within approximately 1.5 hours

Outcome Measure Data

Analysis Population Description

Participants who completed at least one experimental session.

Arm/Group Title	Naltrexone - Asn40Asn	Naltrexone - Asn40Asp/Asp40Asp	Placebo - Asn40Asn	Placebo - Asn40Asp/Asp40Asp
Arm/Group Description	Group that was randomized to receive Naltrexone (50 mg/d) and is homozygote for the Asn40 allele.	Group that was randomized to receive Naltrexone (50mg/d) and carries at least one copy of the Asp40 allele.	The group that was randomized to receive placebo and is homozygote for the Asn40 allele.	Group that was randomized to receive Placebo and carries at least one copy of the Asp40 allele.
Measure Participants	27	48	28	46
BrAC = 0.02 g/dl	2.6825 (2.1146)	2.3482 (1.6194)	2.1480 (1.6452)	2.0560 (1.6726)
BrAC = 0.04 g/dl	2.8571 (2.1907)	2.8601 (2.0094)	2.4949 (1.7798)	2.6832 (1.8504)
BrAc = 0.06 g/dl	3.0688 (2.4364)	3.1548 (2.0981)	2.6786 (2.4767)	2.4627 (1.8025)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Naltrexone - Asn40Asn, Naltrexone - Asn40Asp/Asp40Asp, Placebo - Asn40Asn, Placebo - Asn40Asp/Asp40Asp
	Comments
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	0.55
	Comments	Medication effect: b = 0.14, SE = 0.23, t = 0.61, p = 0.55
	Method	Mixed Models Analysis
	Comments

Statistical Analysis 2

Statistical Analysis Overview	Comparison Group Selection	Naltrexone - Asn40Asn, Naltrexone - Asn40Asp/Asp40Asp, Placebo - Asn40Asn, Placebo - Asn40Asp/Asp40Asp
	Comments
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	0.77
	Comments	Genotype effect: b = -0.11, SE = 0.37, t = -0.30, p = 0.77
	Method	Mixed Models Analysis
	Comments

Statistical Analysis 3

Statistical Analysis Overview	Comparison Group Selection	Naltrexone - Asn40Asn, Naltrexone - Asn40Asp/Asp40Asp, Placebo - Asn40Asn, Placebo - Asn40Asp/Asp40Asp
	Comments
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	0.04
	Comments	BrAC effect: b = 0.30, SE = 0.15, t = 2.02, p = 0.04
	Method	Mixed Models Analysis
	Comments

Statistical Analysis 4

Statistical Analysis Overview	Comparison Group Selection	Naltrexone - Asn40Asn, Naltrexone - Asn40Asp/Asp40Asp, Placebo - Asn40Asn, Placebo - Asn40Asp/Asp40Asp
	Comments
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	0.47
	Comments	Medication by genotype interaction: b = -0.21, SE = 0.29, t = -0.72, p = 0.47
	Method	Mixed Models Analysis
	Comments

Statistical Analysis 5

Statistical Analysis Overview	Comparison Group Selection	Naltrexone - Asn40Asn, Naltrexone - Asn40Asp/Asp40Asp, Placebo - Asn40Asn, Placebo - Asn40Asp/Asp40Asp
	Comments
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	0.19
	Comments	Medication by genotype by BrAC interaction: b = 0.28, SE = 0.21, t = 1.30, p = 0.19
	Method	Mixed Models Analysis
	Comments

4. Primary Outcome

Title	Neural Response to Alcohol Cues
Description	Alcohol taste cues task for functional magnetic resonance imaging (fMRI). Region of Interest (ROI) were atomically defined using the Harvard-Oxford atlas in standard Montreal Neurological Institute (MNI) space, which were transformed into individual participants' native space using Functional Magnetic Resonance Imaging of the Brain Software Library (FSL). Contrast estimates are for Alc > Water cue, and are arbitrary units.
Time Frame	During the alcohol cue exposure fMRI paradigm which is expected to last 45 minutes

Outcome Measure Data

Analysis Population Description

Participants who completed at least one experimental session and whose neuroimaging data was not excluded due to excessive motion (>2 mm translation) and/or poor registration.

Arm/Group Title	Naltrexone - Asn40Asn	Naltrexone - Asn40Asp/Asp40Asp	Placebo - Asn40Asn	Placebo - Asn40Asp/Asp40Asp
Arm/Group Description	Group that was randomized to receive Naltrexone (50 mg/d) and is homozygote for the Asn40 allele.	Group that was randomized to receive Naltrexone (50mg/d) and carries at least one copy of the Asp40 allele.	The group that was randomized to receive placebo and is homozygote for the Asn40 allele.	Group that was randomized to receive Placebo and carries at least one copy of the Asp40 allele.
Measure Participants	18	23	18	23
Ventral Striatum	1.48 (19.94)	8.07 (13.95)	.53 (13.47)	1.03 (13.54)
Orbitofrontal cortex	.12 (11.75)	4.43 (9.64)	.45 (7.2)	3.56 (6.95)
Anterior Cingulate cortex	3.31 (17.96)	7.04 (13.90)	5.17 (14.24)	9.49 (13.07)

5. Secondary Outcome

Title	Alcohol Self-administration - Number of Drinks
Description	Total number of drinks consumed during the alcohol self-administration task
Time Frame	Alcohol self-administration period was 1 hour long

Outcome Measure Data

Analysis Population Description

Participants who completed at least one experimental session.

Arm/Group Title	Naltrexone - Asn40Asn	Naltrexone - Asn40Asp/Asp40Asp	Placebo - Asn40Asn	Placebo - Asn40Asp/Asp40Asp
Arm/Group Description	Group that was randomized to receive Naltrexone (50 mg/d) and is homozygote for the Asn40 allele.	Group that was randomized to receive Naltrexone (50mg/d) and carries at least one copy of the Asp40 allele.	The group that was randomized to receive placebo and is homozygote for the Asn40 allele.	Group that was randomized to receive Placebo and carries at least one copy of the Asp40 allele.
Measure Participants	27	48	28	46
Mean (Standard Deviation) [drinks consumed]	1.4444 (1.5275)	0.6458 (1.1576)	1.5714 (1.4764)	0.9565 (1.3656)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Naltrexone - Asn40Asn, Naltrexone - Asn40Asp/Asp40Asp, Placebo - Asn40Asn, Placebo - Asn40Asp/Asp40Asp
	Comments
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	0.14
	Comments	Medication effect: F(1,71) = 2.24, p = 0.14
	Method	Poisson Regression
	Comments

Statistical Analysis 2

Statistical Analysis Overview	Comparison Group Selection	Naltrexone - Asn40Asn, Naltrexone - Asn40Asp/Asp40Asp, Placebo - Asn40Asn, Placebo - Asn40Asp/Asp40Asp
	Comments
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	0.02
	Comments	Genotype effect: F(1, 71) = 5.79, p = 0.02
	Method	Poisson
	Comments

Statistical Analysis 3

Statistical Analysis Overview	Comparison Group Selection	Naltrexone - Asn40Asn, Naltrexone - Asn40Asp/Asp40Asp, Placebo - Asn40Asn, Placebo - Asn40Asp/Asp40Asp
	Comments
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	0.41
	Comments	Medication by genotype interaction: F(1, 70) = 0.68, p = 0.41.
	Method	Poisson
	Comments

Adverse Events

Time Frame	Adverse event data were collected immediately prior to alcohol infusion while on naltrexone and while on placebo (2 time points). This data was collected twice for each participant, once while they were on placebo and once while they were on naltrexone.
Adverse Event Reporting Description	Adverse events are defined as any symptom endorsed on the Side Effects Checklist (SAFTEE). The instructions on the SAFTEE are, "Have you noticed any of the following symptoms within the last 6 hours? If yes, how severe were the symptoms? Do you believe these symptoms were caused by the study medication?"
Arm/Group Title	Naltrexone		Sugar Pill
Arm/Group Description	Naltrexone 50 mg/day Naltrexone: Naltrexone is an opioid receptor antagonist with highest affinity for mu opioid receptors		Matched placebo Placebo: Sugar pill, matched to the active study medication in capsule size and color
All Cause Mortality
	Naltrexone		Sugar Pill
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	0/75 (0%)		0/74 (0%)
Serious Adverse Events
	Naltrexone		Sugar Pill
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	0/75 (0%)		0/74 (0%)
Other (Not Including Serious) Adverse Events
	Naltrexone		Sugar Pill
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	35/75 (46.7%)		22/74 (29.7%)
Eye disorders
Yellow Eyes	0/75 (0%)		0/74 (0%)
Blurred vision	3/75 (4%)		0/74 (0%)
Gastrointestinal disorders
Abdominal pain or cramps	5/75 (6.7%)		4/74 (5.4%)
Nausea or vomiting	8/75 (10.7%)		2/74 (2.7%)
General disorders
Irritability or anger	7/75 (9.3%)		0/74 (0%)
Increased desire for sex	4/75 (5.3%)		3/74 (4.1%)
Nervousness	5/75 (6.7%)		3/74 (4.1%)
Ringing in the ears	2/75 (2.7%)		1/74 (1.4%)
Decrease in appetite	11/75 (14.7%)		2/74 (2.7%)
Depression	2/75 (2.7%)		1/74 (1.4%)
Fatigue	18/75 (24%)		8/74 (10.8%)
Difficulty in staying awake	10/75 (13.3%)		4/74 (5.4%)
Increase in appetite	3/75 (4%)		3/74 (4.1%)
Drowsiness	15/75 (20%)		5/74 (6.8%)
Headache	4/75 (5.3%)		4/74 (5.4%)
Night sweats	1/75 (1.3%)		2/74 (2.7%)
Mental confusion	3/75 (4%)		1/74 (1.4%)
Anxiety	7/75 (9.3%)		3/74 (4.1%)
Joint or muscle pain	2/75 (2.7%)		1/74 (1.4%)
Dizziness	3/75 (4%)		1/74 (1.4%)
Sexual problems	1/75 (1.3%)		0/74 (0%)
Difficulty sleeping	8/75 (10.7%)		6/74 (8.1%)
Fever or chills	1/75 (1.3%)		1/74 (1.4%)
Decreased desire for sex	2/75 (2.7%)		0/74 (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.