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Trial record 1 of 1 for:    mifepristone gary wand
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INIA Stress and Chronic Alcohol Interactions: Glucocorticoid Antagonists in Heavy Drinkers

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ClinicalTrials.gov Identifier: NCT02989662
Recruitment Status : Recruiting
First Posted : December 12, 2016
Last Update Posted : August 6, 2019
Sponsor:
Collaborator:
National Institute on Alcohol Abuse and Alcoholism (NIAAA)
Information provided by (Responsible Party):
Johns Hopkins University

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.

Condition or disease Intervention/treatment Phase
Alcohol Use Disorder Drug: Mifepristone Drug: Placebo - Cap Not Applicable

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.

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Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 150 participants
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Triple (Participant, Investigator, Outcomes Assessor)
Primary Purpose: Basic Science
Official Title: Glucocorticoid Antagonists in Heavy Drinkers: Effects on fMRI Connectivity, Withdrawal and Drinking
Study Start Date : February 2016
Estimated Primary Completion Date : January 2022
Estimated Study Completion Date : January 2022

Resource links provided by the National Library of Medicine

MedlinePlus related topics: Steroids

Arm Intervention/treatment
Active Comparator: 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 Name: Korlym

Placebo Comparator: Placebo - Cap
This is an inactive compound which appears physically identical to active medication.
Drug: Placebo - Cap
Participants receive 6 doses




Primary Outcome Measures :
  1. fMRI function connectivity [ Time Frame: Change from baseline to day 4 of MIFE dosing ]
    fMRI data including resting state and alcohol cue induced measures


Secondary Outcome Measures :
  1. Alcohol motivated responding [ Time Frame: single session on study day 5 ]
    Participants can earn up to 5 standard drinks during a 1-hr session.

  2. Alcohol sensitivity [ Time Frame: single session on study day 6 ]
    Subjective and physiological effects of alcohol are measured repeatedly during a 4-hr session



Information from the National Library of Medicine

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Ages Eligible for Study:   21 Years to 55 Years   (Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   Yes
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.

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT02989662


Contacts
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Contact: Gary Wand, MD 410-955-3921 gwand1@jhmi.edu
Contact: Mary E McCaul, PhD 410-955-9526 mmccaul1@jhmi.edu

Locations
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United States, Maryland
Integrated Program for Substance Abuse Research Recruiting
Baltimore, Maryland, United States, 21205
Contact: Mary E McCaul, PhD    410-955-9526    mmccaul1@jhmi.edu   
Contact: JoAnna Mathena, MS    410-955-9524    jmathen5@jhmi.edu   
Sponsors and Collaborators
Johns Hopkins University
National Institute on Alcohol Abuse and Alcoholism (NIAAA)
Investigators
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Principal Investigator: Gary Wand, MD Johns Hopkins University
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Responsible Party: Johns Hopkins University
ClinicalTrials.gov Identifier: NCT02989662    
Other Study ID Numbers: IRB00138426
U01AA020890 ( U.S. NIH Grant/Contract )
AA020890 ( Other Identifier: Other )
First Posted: December 12, 2016    Key Record Dates
Last Update Posted: August 6, 2019
Last Verified: August 2019
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: No
Additional relevant MeSH terms:
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Mifepristone
Alcoholism
Alcoholic Intoxication
Alcohol-Related Disorders
Substance-Related Disorders
Chemically-Induced Disorders
Mental Disorders
Abortifacient Agents, Steroidal
Abortifacient Agents
Reproductive Control Agents
Physiological Effects of Drugs
Contraceptives, Oral, Synthetic
Contraceptives, Oral
Contraceptive Agents, Female
Contraceptive Agents
Contraceptives, Postcoital, Synthetic
Contraceptives, Postcoital
Hormone Antagonists
Hormones, Hormone Substitutes, and Hormone Antagonists
Luteolytic Agents
Menstruation-Inducing Agents