Clinical Trial: Title: Effect of Opioid Receptor Modulation on Alcohol Self-Administration and Neural Response to Alcohol Cues in Heavy Drinkers: Role of OPRM1 Gene Variation
Study Status: Recruiting
Recruit Status: Recruiting
Study Type: Interventional
Official Title: Effect of Opioid Receptor Modulation on Alcohol Self-Administration and Neural Response to Alcohol Cues in Heavy Drinkers: Role of OPRM1 Gene Variation
Brief Summary:
Background:
Drugs like nalmefene interfere with opioid receptors. This might reduce drinking. The gene OPRM1 determines opioid receptor functions. Researchers want to see if nalmefene affects people s responses to alcohol cues. They also want to compare how nalmefene affects people with different forms of OPRM1.
Objectives:
To test nalmefene s effects on alcohol self-infusion and responses to alcohol cues. To test the role of different forms of OPRM1 on these effects.
Eligibility:
Healthy heavy drinkers ages 21 60:
Women: over 15 drinks weekly
Men: over 20 drinks weekly
Design:
Participants will be screened with:
Medical history
Physical exam
Heart, blood, and urine tests
Questionnaires
Participants will have three 10-hour visits and one 2-hour follow-up visit. They will take a taxi. Visits are about 1 week apart.
Before visits, participants cannot drink alcohol for 1 day or take medicine for 3 days.
All study visits:
Questionnaires
Heart monitor
Two-hour alcohol session: A needle guides a
Detailed Summary:
Previous studies have shown that the opioid receptor modulator nalmefene can reduce heavy drinking among alcoholics. Genetic variation at the micro-opioid receptor gene locus, OPRM1, specifically the A118G polymorphism, is associated with differential subjective responses to alcohol. Further, the A118G polymorphism has been shown to moderate the effect of opioid receptor modulators on alcohol consumption. However, the role of A118G on nalmefene s effectivenes, and the neural substrates underlying nalmefene s therapeutic effect remain to be explored in humans.
Objective: To evaluate the effect of nalmefene on alcohol self-infusion and neural response to alcohol cues in healthy male and female heavy drinkers, and to examine the role of the OPRM1 A118G polymorphism on this effect.
Study population: Participants will be 21-60 year-old male and female heavy drinkers in good health, as determined by medical history, physical exam, and ECG and lab tests. Participants with current Axis-I mood, anxiety or substance use diagnoses, except alcohol dependence, will be excluded. Participants will be divided into 2 genotypic groups: Group 1 (AA) will include participants homozygous for the major 118A allele (118AA genotype), and group 2 (GX) will include participants carrying 1 or 2 copies of the variant 118G allele (118AG or 118GG genotype).
Design: Participants will undergo 3 study sessions. In the first session, participants will complete an intravenous alcohol self-administration (IV-ASA) where they will have an open bar phase to determine their baseline level of alcohol consumption in the laboratory, as well as to obtain data on tolerability and subjective measures of alcohol effects. In the second and third sessions, participants will receive a single dose of either nalmefene or pla
Sponsor: National Institute on Alcohol Abuse and Alcoholism (NIAAA)
Current Primary Outcome:
- Nalmefene-induced BOLD signal changes in neural regions associated with alcohol reward processing, including ventral striatum, amygdala, and insula [ Time Frame: 1 hr post-study drug ]
- Nalmefene-induced changes in IV alcohol self-administration [ Time Frame: post-study drug ]
Original Primary Outcome: Same as current
Current Secondary Outcome:
- Nalmefene-induced BOLD signal changes in neural processing of aversive stimuli during fMRI [ Time Frame: 1 hour post-study drug ]
- Genotypic modulation (at the OPRM1 118 location) of Nalmafene's effects on primary outcome measures (BOLD signal change during alcohol reward processing and IV alcohol self-administration). [ Time Frame: 1 hr post-study drug ]
Original Secondary Outcome: Same as current
Information By: National Institutes of Health Clinical Center (CC)
Dates:
Date Received: December 23, 2015
Date Started: December 18, 2015
Date Completion: July 31, 2020
Last Updated: April 20, 2017
Last Verified: April 3, 2017
