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

NCT02989662 | Completed Phase 1 Results DMC FDA Drug

• 3 other identifiers: IRB00138426U01AA020890AA020890
• Study Type: interventional
• Target: 65
• Locations: 1 country
• Sites: 1

Brief Summary

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.

Conditions

Alcohol Use Disorder

Outcome Measures

Primary Outcomes (1)

• Change in Blood Oxygen Level Dependent (BOLD) fMRI Signal for Alcohol Versus Non-alcohol Stimuli

  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 Outcomes (2)

• Mean of Alcohol Motivated Responses Made

  single session on study day 5

• Alcohol Motivated Responding - Number of Drinks Earned

  single session on study day 5

Study Arms (4)

Alcohol Use Disorder - Mifepristone

ACTIVE COMPARATOR

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

Alcohol Use Disorder - Placebo

PLACEBO COMPARATOR

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

Healthy Control - Mifepristone

ACTIVE COMPARATOR

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

Healthy Control - Placebo

PLACEBO COMPARATOR

Healthy control participants who were randomized to receive placebo. This is an inactive compound which appears physically identical to active medication.

Drug: Placebo - Cap

Interventions

Mifepristone DRUG

Participants receive 6 doses.

Also known as: Korlym

Alcohol Use Disorder - Mifepristone; Healthy Control - Mifepristone

Placebo - Cap DRUG

Participants receive 6 doses

Alcohol Use Disorder - Placebo; Healthy Control - Placebo

Eligibility Criteria

• Age: 21 Years - 55 Years
• Sex: all
• Healthy Volunteers: Yes
• Age Groups: Adult (18-64)

You may qualify if:

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

You may not qualify if:

• 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.

Sponsors & Collaborators

• Johns Hopkins University: lead
• National Institute on Alcohol Abuse and Alcoholism (NIAAA): collaborator

Study Sites (1)

Integrated Program for Substance Abuse Research

Baltimore, Maryland, 21205, United States

Location

MeSH Terms

Conditions

Alcoholism

Interventions

Mifepristone

Condition Hierarchy (Ancestors)

Alcohol-Related Disorders; Substance-Related Disorders; Chemically-Induced Disorders; Mental Disorders

Intervention Hierarchy (Ancestors)

Estrenes; Estranes; Steroids; Fused-Ring Compounds; Polycyclic Compounds

Results Point of Contact

• Title: Mary E McCaul, Ph.D.
• Organization: Johns Hopkins University School of Medicine

mmccaul1@jhmi.edu

4437225728

Study Officials

• Mary E McCaul, PhD

  Johns Hopkins University

  PRINCIPAL INVESTIGATOR

Publication Agreements

• PI is Sponsor Employee: No
• Restrictive Agreement: No

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: RANDOMIZED
• Masking: TRIPLE
• Who Masked: PARTICIPANT, INVESTIGATOR, OUTCOMES ASSESSOR
• Purpose: BASIC SCIENCE
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: December 5, 2016
• First Posted: December 12, 2016
• Study Start: September 26, 2017
• Primary Completion: January 31, 2024
• Study Completion: January 31, 2024
• Last Updated: May 30, 2025
• Results First Posted: May 30, 2025

Record last verified: 2025-05

Data Sharing

• IPD Sharing: Will not share

Locations

US (1)