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

NCT ID: NCT02989662

Last Updated: 2025-05-30

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: PHASE1/PHASE2
• Total Enrollment: 65 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2017-09-26
• Study Completion Date: 2024-01-31

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.

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.

Conditions

Alcohol Use Disorder

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: PARALLEL
• Primary Study Purpose: BASIC_SCIENCE
• Blinding Strategy: TRIPLE

Study Groups

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.

Group Type: ACTIVE_COMPARATOR

Mifepristone

Intervention Type: DRUG

Participants receive 6 doses.

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.

Group Type: PLACEBO_COMPARATOR

Placebo - Cap

Intervention Type: DRUG

Participants receive 6 doses

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.

Group Type: ACTIVE_COMPARATOR

Mifepristone

Intervention Type: DRUG

Participants receive 6 doses.

Healthy Control - Placebo

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

Group Type: PLACEBO_COMPARATOR

Placebo - Cap

Intervention Type: DRUG

Participants receive 6 doses

Interventions

Mifepristone

Participants receive 6 doses.

Intervention Type: DRUG

Placebo - Cap

Participants receive 6 doses

Intervention Type: DRUG

Other Intervention Names

Korlym

Eligibility Criteria

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.

• Minimum Eligible Age: 21 Years
• Maximum Eligible Age: 55 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: Yes

Sponsors

National Institute on Alcohol Abuse and Alcoholism (NIAAA)

NIH

Sponsor Role: collaborator

Johns Hopkins University

OTHER

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

Mary E McCaul, PhD

Role: PRINCIPAL_INVESTIGATOR

Johns Hopkins University

Locations

Integrated Program for Substance Abuse Research

Baltimore, Maryland, United States

Countries

United States

Provided Documents

Document Type: Study Protocol and Statistical Analysis Plan

View Document

Other Identifiers

U01AA020890

Identifier Type: NIH

Identifier Source: secondary_id

View Link

AA020890

Identifier Type: OTHER

Identifier Source: secondary_id

IRB00138426

Identifier Type: -

Identifier Source: org_study_id