Title: Effect of Opioid Receptor Modulation on Alcohol Self-Administration and Neural Response to Alcohol Cues in Heavy Drinkers: Role of OPRM1 Gene Variation

NCT02639273 | Completed Phase 1 FDA Drug

• 2 other identifiers: 16003716-AA-0037
• Study Type: interventional
• Target: 13
• Locations: 1 country
• Sites: 1

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 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.

Conditions

AUD

Keywords

Alcohol Infusion study; Nalmefene; fMRI; Genetics; NIAAA

Outcome Measures

Primary Outcomes (2)

• Nalmefene-induced BOLD signal changes in neural regions associated with alcohol reward processing, including ventral striatum, amygdala, and insula

  functional MRI measure of brain activation.

  Post-administration

• Nalmefene-induced changes in IV alcohol self-administration

  human laboratory alcohol consumption measure.

  Post-administration

Secondary Outcomes (2)

• Nalmefene-induced BOLD signal changes in neural processing of aversive stimuli during fMRI

  Post-adminstration

• 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).

  Post-administration

Study Arms (2)

Drug

EXPERIMENTAL

single dose nalmefene

Drug: Nalmefene

Placebo

PLACEBO COMPARATOR

single dose placebo

Other: Placebo

Interventions

Nalmefene DRUG

Active Drug

Drug

Placebo OTHER

Single Dose Placebo

Placebo

Eligibility Criteria

• Age: 21 Years - 60 Years
• Sex: all
• Healthy Volunteers: Yes
• Age Groups: Adult (18-64)

You may not qualify if:

• Male and female participants between 21-60 years of age.
• Male participants must have consumed an average of greater than 14 standard drinks per week, and females must have consumed an average of greater than 7 standard drinks per week during the past 3 months \[assessment: 90-day timeline followback (TLFB)completed at screening visit\].
• In addition, participants must have on average at least 1 binge drinking day per week during the last 90 days, defined as a day in which 4 or more standard drinks were consumed for females and 5 or more standard drinks were consumed for males. Average number of binge drinking days will be calculated based on total number of binge drinking days from the TLFB (e.g., for 90 days worth of data, participants with a total of 13 or more binge drinking days will be eligible).
• Participants must be willing and able to refrain from using alcohol one day prior to each study, and non-prescription medication for 3 days prior to each visit \[assessment: medical history\].
• Use of adequate method of birth control during the study, if female is sexually active and is not surgically sterilized. Adequate methods of contraception include: use of oral contraceptives; use of barrier method of contraceptive; use of an approved IUD or other long-acting reversible contraceptive (LARC); have a male sexual partner who is surgically sterilized; or have exclusively female sexual partner(s) \[assessment: medical history\].
• Current or prior history of major medical illness, including CNS, cardiovascular, respiratory, gastrointestinal, hepatic, renal, endocrine, or reproductive disorders \[assessment: clinically significant findings on medical history and physical exam, ECG, laboratory tests\].
• Participation in any other pharmacological intervention study within 4 months prior to the start of this study \[assessment: medical history\].
• Positive hepatitis A, B Antigen, or C, or HIV test \[assessment: laboratory test\].
• An aspartate transaminase (AST) / alanine transaminase (ALT) ratio 3 times greater than the normal limit \[assessment: laboratory test\].
• Diagnosis of Axis-I anxiety disorders or major depressive disorders in the past 12 months \[assessment: SCID interview\].
• Lifetime diagnosis of Axis-I bipolar disorders or psychotic disorders \[assessment: SCID interview\].
• Suicidal ideation in the past 6 months or suicidal behavior in the past 12 months \[assessment: Columbia Suicide Severity Rating Scale\].
• Positive result on urine drug screen or breathalyzer test during screening. Positive urine drug screen or breathalyzer reading during more than 1 study visit will result in participant withdrawal from the study \[assessment: laboratory tests and breathalyzer test performed at screening or update visit under 14-AA-0181 most proximal to enrollment\].
• Currently (i.e., at the time of screening) seeking treatment for alcohol problems or have undergone inpatient or outpatient detoxification or treatment for alcohol problems in the past 6 months. \[assessment: medical history and physical exam\].
• Lactose intolerance or rare hereditary problems of galactose intolerance, Lapp lactase deficiency, or glucose-galactose malabsorption \[assessment: medical history and physical exam\].

Sponsors & Collaborators

• National Institute on Alcohol Abuse and Alcoholism (NIAAA): lead

Study Sites (1)

National Institutes of Health Clinical Center

Bethesda, Maryland, 20892, United States

Location

Related Publications (1)

• Gowin JL, Sloan ME, Kirk-Provencher KT, Rosenblatt SL, Penner AE, Stangl BL, Byrd ND, Swan JE, Ramchandani VA. Opioid receptor antagonism and neural response to monetary rewards: Pilot studies in light and heavy alcohol users. J Psychopharmacol. 2023 Sep;37(9):937-941. doi: 10.1177/02698811231191707. Epub 2023 Aug 2.

  PMID: 37530456 DERIVED

Related Links

• NIH Clinical Center Detailed Web Page

MeSH Terms

Interventions

nalmefene

Study Officials

• Vijay A Ramchandani, Ph.D.

  National Institute on Alcohol Abuse and Alcoholism (NIAAA)

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: RANDOMIZED
• Masking: DOUBLE
• Who Masked: PARTICIPANT, INVESTIGATOR
• Purpose: OTHER
• Intervention Model: CROSSOVER
• Sponsor Type: NIH
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: December 23, 2015
• First Posted: December 24, 2015
• Study Start: June 8, 2016
• Primary Completion: December 8, 2023
• Study Completion: December 8, 2023
• Last Updated: November 21, 2025

Record last verified: 2025-10-23

Locations

US (1)