Title: Effect of Opioid Receptor Modulation on Alcohol Self-Administration and Neural Response to Alcohol Cues in Heavy Drinkers: Role of OPRM1 Gene Variation
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|ClinicalTrials.gov Identifier: NCT02639273|
Recruitment Status : Recruiting
First Posted : December 24, 2015
Last Update Posted : January 14, 2021
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.
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.
Healthy heavy drinkers ages 21 60:
Women: over 15 drinks weekly
Men: over 20 drinks weekly
Participants will be screened with:
Heart, blood, and urine tests
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:
Two-hour alcohol session: A needle guides a thin plastic tube into a vein in each arm. One tube receives alcohol. The other draws blood. Participants give themselves alcohol by pressing a button on a computer.
Relaxing at the center until breath alcohol falls below 0.02 percent, or for 3 hours.
Visits 2 and 3:
Swallowing nalmefene or placebo.
One-hour brain MRI: Participants lie on a table with a coil on their head. They press buttons in response to computer cues.
Follow-up visit: participants will discuss their drinking habits.
|Condition or disease||Intervention/treatment||Phase|
|AUD||Drug: Nalmefene Other: Placebo||Phase 1|
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 placebo, in counter-balanced order, before completing functional magnetic resonance imaging (fMRI) scans and IV-ASA procedures. The fMRI scans will include a task where participants will see cues that indicate the possibility of earning alcohol rewards to examine the neural substrates involved in processing alcohol cues, and a task designed to measure neural responses during anticipation and processing of aversive events. The difference in alcohol self-infusions between the two sessions will be compared between the two genotypic groups.
Outcome measures: The primary outcome measures are: (1) nalmefene-induced changes in IV alcohol self-administration; (2) nalmefene-induced BOLD signal changes in neural regions associated with alcohol reward processing, including ventral striatum, amygdala, and insula.;Secondary outcome measures include: (1) Nalmefene-induced BOLD signal changes in neural processing of aversive stimuli during fMRI; (2) Genotypic modulation (at the OPRM1 118 location) of nalmefene s effects on primary outcome measures (BOLD signal change during alcohol reward processing and IV alcohol self-administration).
|Study Type :||Interventional (Clinical Trial)|
|Estimated Enrollment :||60 participants|
|Intervention Model:||Crossover Assignment|
|Masking:||Double (Participant, Investigator)|
|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|
|Actual Study Start Date :||June 8, 2016|
|Estimated Primary Completion Date :||December 31, 2021|
|Estimated Study Completion Date :||December 31, 2021|
single dose nalmefene
Placebo Comparator: Placebo
single dose placebo
Single Dose Placebo
- Nalmefene-induced BOLD signal changes in neural regions associated with alcohol reward processing, including ventral striatum, amygdala, and insula [ Time Frame: Post-administration ]functional MRI measure of brain activation.
- Nalmefene-induced changes in IV alcohol self-administration [ Time Frame: Post-administration ]human laboratory alcohol consumption measure.
- Nalmefene-induced BOLD signal changes in neural processing of aversive stimuli during fMRI [ Time Frame: Post-adminstration ]functional MRI measure of brain activation.
- 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: Post-administration ]human laboratory alcohol consumption measure.
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): NCT02639273
|Contact: Vijay A Ramchandani, Ph.D.||(301) 402-8527||NIAAASHPResearch@mail.nih.gov|
|United States, Maryland|
|National Institutes of Health Clinical Center, 9000 Rockville Pike||Recruiting|
|Bethesda, Maryland, United States, 20892|
|Contact: For more information at the NIH Clinical Center contact Office of Patient Recruitment (OPR) 800-411-1222 ext TTY8664111010 email@example.com|
|Principal Investigator:||Vijay A Ramchandani, Ph.D.||National Institute on Alcohol Abuse and Alcoholism (NIAAA)|