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

Alcohol Use Disorder Clinical Trial

Official title:

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

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT02989662
• Other study ID #: IRB00138426
• Secondary ID: U01AA020890AA020
• Status: Completed
• Phase: Phase 1/Phase 2
• Start date: September 26, 2017
• Est. completion date: January 31, 2024

Study information

• Verified date: May 2024
• Source: Johns Hopkins University
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 65
• Est. completion date: January 31, 2024
• Est. primary completion date: January 31, 2024
• Accepts healthy volunteers: Accepts Healthy Volunteers
• Gender: All
• Age group: 21 Years to 55 Years

Eligibility

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.

Related Conditions & MeSH terms

• Alcohol Use Disorder
• Alcoholic Intoxication
• Alcoholism

Intervention

Drug:
• Mifepristone
Participants receive 6 doses.
• Placebo - Cap
Participants receive 6 doses

Locations

Country	Name	City	State
United States	Integrated Program for Substance Abuse Research	Baltimore	Maryland

Sponsors (2)

Lead Sponsor	Collaborator
Johns Hopkins University	National Institute on Alcohol Abuse and Alcoholism (NIAAA)

Country where clinical trial is conducted

United States, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	fMRI function connectivity	fMRI data including resting state and alcohol cue induced measures	Change from baseline to day 4 of MIFE dosing
Secondary	Alcohol motivated responding	Participants can earn up to 5 standard drinks during a 1-hr session.	single session on study day 5
Secondary	Alcohol sensitivity	Subjective and physiological effects of alcohol are measured repeatedly during a 4-hr session	single session on study day 6