INIA Stress and Chronic Alcohol Interactions: Glucocorticoid Antagonists in Heavy Drinkers

May 29, 2025 updated by: Johns Hopkins University

Glucocorticoid Antagonists in Heavy Drinkers: Effects on fMRI Connectivity, Withdrawal and Drinking

In alcohol use disorder (AUD) and matched healthy control (HC) men and women, the proposed research examines the effects of MIFE, with demonstrated preclinical effects on drinking-related behaviors, compared with placebo on a breadth of alcohol-related measures. All subjects will be randomized to daily MIFE or placebo. Before and during medication, AUD and HC subjects undergo fMRI scanning measuring resting-state functional connectivity and alcohol cue-induced brain activation focused on brain reward and stress pathways. All subjects are admitted to the Clinical Research Unit; AUD subjects undergo supervised alcohol withdrawal with daily measurements of alcohol craving and symptom severity. Using validated human laboratory procedures in AUD subjects, this study will examine the effects of stress on motivation to drink and alcohol sensitivity/reward as a function of GR antagonism.

Study Overview

Status

Completed

Conditions

Intervention / Treatment

Detailed Description

Cortisol (CORT) is a glucocorticoid hormone, often associated with response to stress and playing a key role in alcohol use and problems. First, acute alcohol administration increases CORT, which in turn amplifies the mesolimbic dopamine reward signal. Second, alcohol withdrawal elevates CORT levels in AUD compared with healthy control subjects, and CORT levels in early abstinence predict subsequent relapse to drinking. Finally, the magnitude of CORT response to external stressors predicts motivation to work for and consumption of alcohol in the human laboratory and in the natural environment. Importantly, recent studies in rodents and humans have demonstrated that blocking CORT activity using a glucocorticoid receptor (GR) antagonist reduces these effects of CORT on alcohol behaviors, indicating a causal role for glucocorticoids in these relationships. In alcohol use disorder (AUD) and matched healthy control (HC) men and women, the proposed research examines the effects of MIFE, with demonstrated preclinical effects on drinking-related behaviors, compared to placebo on a breadth of alcohol-related measures. All subjects will be randomized to daily MIFE or placebo. Before and during medication, AUD and HC subjects undergo fMRI scanning measuring resting-state functional connectivity and alcohol cue-induced brain activation focused on brain reward and stress pathways. All subjects are admitted to the Clinical Research Unit; AUD subjects undergo supervised alcohol withdrawal with daily measurements of alcohol craving and symptom severity. Using validated human laboratory procedures in AUD subjects, this study will examine the effects of stress on motivation to drink and alcohol sensitivity/reward as a function of GR antagonism. This work will help pave the way for improved pharmacotherapies that target stress and reward pathways in the brain involved in initiating and maintaining drinking.

Study Type

Interventional

Enrollment (Actual)

65

Phase

  • Phase 2
  • Phase 1

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Locations

  • United States
    • Maryland
      • Baltimore, Maryland, United States, 21205
        • Integrated Program for Substance Abuse Research

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

21 years to 55 years (Adult)

Accepts Healthy Volunteers

Yes

Description

Inclusion Criteria:

  • Nontreatment seeking AUD volunteers
  • English speaking
  • healthy
  • Not pregnant or nursing

Exclusion Criteria:

  • Women on hormonal birth control, pregnant or nursing
  • Current health or psychiatric problems
  • Potassium level below normal
  • Any medication or health condition that is known to interact with MIFE or CORT metabolism
  • History of metal implantation that would preclude MRI scan.

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: Basic Science
  • Allocation: Randomized
  • Interventional Model: Parallel Assignment
  • Masking: Triple

Arms and Interventions

Participant Group / Arm
Intervention / Treatment
Active Comparator: Alcohol Use Disorder - Mifepristone
Participants diagnosed with alcohol use disorder who were randomized to receive mifepristone. Mifepristone is a high affinity antagonist of the glucocorticoid receptor (GR). It is FDA approved to treatment hyperglycemia caused by high cortisol levels in adults with endogenous Cushing's syndrome.
Drug: Mifepristone
Participants receive 6 doses.
Other Names:
  • Korlym
Placebo Comparator: Alcohol Use Disorder - Placebo
Participants diagnosed with alcohol use disorder who were randomized to receive placebo. This is an inactive compound which appears physically identical to active medication.
Drug: Placebo - Cap
Participants receive 6 doses
Active Comparator: Healthy Control - Mifepristone
Healthy control participants who were randomized to receive mifepristone. Mifepristone is a high affinity antagonist of the glucocorticoid receptor (GR). It is FDA approved to treatment hyperglycemia caused by high cortisol levels in adults with endogenous Cushing's syndrome.
Drug: Mifepristone
Participants receive 6 doses.
Other Names:
  • Korlym
Placebo Comparator: Healthy Control - Placebo
Healthy control participants who were randomized to receive placebo. This is an inactive compound which appears physically identical to active medication.
Drug: Placebo - Cap
Participants receive 6 doses

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Change in Blood Oxygen Level Dependent (BOLD) fMRI Signal for Alcohol Versus Non-alcohol Stimuli
Time Frame: Change from baseline (Day 1) to day 4 of MIFE dosing
Participants observed alcohol and neutral cues during functional MRI (fMRI) scans. Larger numbers indicate greater activation to alcohol versus non alcohol stimuli. Mean response Pre and Post medication (mifepristone (MIFE), placebo), is measured. The greater the number the greater the reactivity to alcohol-related cues.
Change from baseline (Day 1) to day 4 of MIFE dosing

Secondary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Mean of Alcohol Motivated Responses Made
Time Frame: single session on study day 5
Participants made alcohol motivated responses with a computer mouse to earn either alcohol drinks or money. Each mouse click equaled one response. Mean of all responses made are reported.
single session on study day 5
Alcohol Motivated Responding - Number of Drinks Earned
Time Frame: single session on study day 5
Participants can earn up to 10 drinks during a 1-hr session. Each drink was the equivalent of 0.5 standard drink.
single session on study day 5

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

Johns Hopkins University

Collaborators

National Institute on Alcohol Abuse and Alcoholism (NIAAA)

Investigators

  • Principal Investigator: Mary E McCaul, PhD, Johns Hopkins University

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start (Actual)

September 26, 2017

Primary Completion (Actual)

January 31, 2024

Study Completion (Actual)

January 31, 2024

Study Registration Dates

First Submitted

December 5, 2016

First Submitted That Met QC Criteria

December 7, 2016

First Posted (Estimated)

December 12, 2016

Study Record Updates

Last Update Posted (Actual)

May 30, 2025

Last Update Submitted That Met QC Criteria

May 29, 2025

Last Verified

May 1, 2025

More Information

Terms related to this study

Additional Relevant MeSH Terms

Other Study ID Numbers

  • IRB00138426
  • U01AA020890 (U.S. NIH Grant/Contract)
  • AA020890 (Other Identifier: Other)

Plan for Individual participant data (IPD)

Plan to Share Individual Participant Data (IPD)?

NO

Drug and device information, study documents

Studies a U.S. FDA-regulated drug product

Yes

Studies a U.S. FDA-regulated device product

No

product manufactured in and exported from the U.S.

No

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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