- ICH GCP
- US Clinical Trials Registry
- Clinical Trial NCT02026011
Naltrexone for Individuals of East Asian Descent
June 27, 2019 updated by: Lara Ray, PhD, University of California, Los Angeles
Optimizing Naltrexone for Individuals of East Asian Descent
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.
Study Overview
Status
Completed
Conditions
Intervention / Treatment
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 Type
Interventional
Enrollment (Actual)
87
Phase
- Phase 2
Contacts and Locations
This section provides the contact details for those conducting the study, and information on where this study is being conducted.
Study Locations
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California
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Los Angeles, California, United States, 90095
- UCLA Addictions Laboratory
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-
Participation Criteria
Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.
Eligibility Criteria
Ages Eligible for Study
21 years to 65 years (Adult, Older Adult)
Accepts Healthy Volunteers
No
Genders Eligible for Study
All
Description
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)
Study Plan
This section provides details of the study plan, including how the study is designed and what the study is measuring.
How is the study designed?
Design Details
- Primary Purpose: Treatment
- Allocation: Randomized
- Interventional Model: Crossover Assignment
- Masking: Triple
Arms and Interventions
Participant Group / Arm |
Intervention / Treatment |
---|---|
Experimental: Naltrexone
Naltrexone 50 mg/day
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Naltrexone is an opioid receptor antagonist with highest affinity for mu opioid receptors
Other Names:
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Placebo Comparator: Sugar pill
Matched placebo
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Sugar pill, matched to the active study medication in capsule size and color
Other Names:
|
What is the study measuring?
Primary Outcome Measures
Outcome Measure |
Measure Description |
Time Frame |
---|---|---|
Subjective Response - Craving for Alcohol
Time Frame: 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.
|
The AUQ was administered across a period of approximately 1.5 hours.
|
Subjective Response - Stimulation
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
|
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.
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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
|
Subjective Response - Sedation
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
|
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.
|
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
|
Neural Response to Alcohol Cues
Time Frame: During the alcohol cue exposure fMRI paradigm which is expected to last 45 minutes
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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.
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During the alcohol cue exposure fMRI paradigm which is expected to last 45 minutes
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Secondary Outcome Measures
Outcome Measure |
Measure Description |
Time Frame |
---|---|---|
Alcohol Self-administration - Number of Drinks
Time Frame: Alcohol self-administration period was 1 hour long
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Total number of drinks consumed during the alcohol self-administration task
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Alcohol self-administration period was 1 hour long
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Collaborators and Investigators
This is where you will find people and organizations involved with this study.
Publications and helpful links
The person responsible for entering information about the study voluntarily provides these publications. These may be about anything related to the study.
Helpful Links
Study record dates
These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.
Study Major Dates
Study Start
December 1, 2013
Primary Completion (Actual)
September 1, 2016
Study Completion (Actual)
September 1, 2016
Study Registration Dates
First Submitted
December 30, 2013
First Submitted That Met QC Criteria
December 30, 2013
First Posted (Estimate)
January 1, 2014
Study Record Updates
Last Update Posted (Actual)
July 17, 2019
Last Update Submitted That Met QC Criteria
June 27, 2019
Last Verified
June 1, 2019
More Information
Terms related to this study
Additional Relevant MeSH Terms
Other Study ID Numbers
- NTX-AA
- R01AA021744 (U.S. NIH Grant/Contract)
Plan for Individual participant data (IPD)
Plan to Share Individual Participant Data (IPD)?
NO
This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.
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