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Naltrexone for Individuals of East Asian Descent

Information source: University of California, Los Angeles
ClinicalTrials.gov processed this data on August 23, 2015
Link to the current ClinicalTrials.gov record.

Condition(s) targeted: Alcohol Use Disorder

Intervention: Naltrexone (Drug); Placebo (Drug)

Phase: Phase 2

Status: Recruiting

Sponsored by: University of California, Los Angeles

Official(s) and/or principal investigator(s):
Lara Ray, PhD, Principal Investigator, Affiliation: University of California, Los Angeles

Overall contact:
Katy Lunny, BA, Phone: 310-206-6756, Email: raylab@psych.ucla.edu

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.

Clinical Details

Official title: Optimizing Naltrexone for Individuals of East Asian Descent

Study design: Allocation: Randomized, Endpoint Classification: Safety/Efficacy Study, Intervention Model: Crossover Assignment, Masking: Double Blind (Subject, Investigator, Outcomes Assessor), Primary Purpose: Treatment

Primary outcome:

Subjective Effects of Alcohol

Neural response to alcohol cues

Secondary outcome: Alcohol self-administration

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.

Eligibility

Minimum age: 21 Years. Maximum age: 65 Years. Gender(s): Both.

Criteria:

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)

Locations and Contacts

Katy Lunny, BA, Phone: 310-206-6756, Email: raylab@psych.ucla.edu

UCLA Addictions Laboratory, Los Angeles, California 90095, United States; Recruiting
Katy Lunny, BA, Phone: 310-206-6756, Email: raylab@psych.ucla.edu
Taylor Rohrbaugh, BA, Phone: 310-206-6756, Email: raylab@psych.ucla.edu
Lara Ray, PhD, Principal Investigator
Additional Information

UCLA Addictions Laboratory

Related 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.

Starting date: December 2013
Last updated: August 18, 2015

Page last updated: August 23, 2015

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