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Naltrexone for Individuals of East Asian Descent

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ClinicalTrials.gov Identifier: NCT02026011
Recruitment Status : Completed
First Posted : January 1, 2014
Last Update Posted : October 27, 2016
Sponsor:
Collaborator:
National Institute on Alcohol Abuse and Alcoholism (NIAAA)
Information provided by (Responsible Party):
Lara Ray, University of California, Los Angeles

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 Type : Interventional  (Clinical Trial)
Actual Enrollment : 72 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 : December 2013
Actual Primary Completion Date : September 2016
Actual Study Completion Date : September 2016

Resource links provided by the National Library of Medicine

U.S. FDA Resources

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 Name: Sugar pill



Primary Outcome Measures :
  1. Subjective Effects of Alcohol [ Time Frame: During the alcohol administration and observation period which is expected to last a total of 4 hours ]
    Biphasic Alcohol Effects Scale (BAES) Alcohol Urge Questionnaire (AUQ)

  2. Neural response to alcohol cues [ Time Frame: During the alcohol cue exposure fMRI paradigm which is expected to last 45 minutes ]
    Alcohol taste cues task for fMRI


Secondary Outcome Measures :
  1. Alcohol self-administration [ Time Frame: Alcohol self-administration period will last 2 hours ]
    Time to first drink and total number of drinks are the primary outcome variables for the alcohol self-administration task



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Ages Eligible for Study:   21 Years to 65 Years   (Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
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)

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT02026011


Locations
United States, California
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

Additional Information:
Publications:
Responsible Party: Lara Ray, Associate Professor, University of California, Los Angeles
ClinicalTrials.gov Identifier: NCT02026011     History of Changes
Other Study ID Numbers: NTX-AA
R01AA021744 ( U.S. NIH Grant/Contract )
First Posted: January 1, 2014    Key Record Dates
Last Update Posted: October 27, 2016
Last Verified: October 2016
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: No

Keywords provided by Lara Ray, University of California, Los Angeles:
alcohol use disorder
naltrexone
Asian American
pharmacogenetics
OPRM1 gene

Additional relevant MeSH terms:
Alcohol Drinking
Drinking Behavior
Naltrexone
Narcotic Antagonists
Physiological Effects of Drugs
Sensory System Agents
Peripheral Nervous System Agents