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| ID | Type | Description | Link |
|---|---|---|---|
| U01AA020890 | U.S. NIH Grant/Contract | View source | |
| AA020890 | Other Identifier | Other |
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| Name | Class |
|---|---|
| National Institute on Alcohol Abuse and Alcoholism (NIAAA) | NIH |
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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.
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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| Label | Type | Description | Intervention Names |
|---|---|---|---|
| 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. |
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| 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. |
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| 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. |
|
| 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. |
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| Name | Type | Description | Arm Group Labels | Other Names |
|---|---|---|---|---|
| Mifepristone | Drug | Participants receive 6 doses. |
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| Measure | Description | Time Frame |
|---|---|---|
| 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 |
| Measure | Description | Time Frame |
|---|---|---|
| Mean of Alcohol Motivated Responses Made | 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 |
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Inclusion Criteria:
Exclusion Criteria:
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| Name | Affiliation | Role |
|---|---|---|
| Mary E McCaul, PhD | Johns Hopkins University | Principal Investigator |
| Facility | Status | City | State | ZIP | Country | Contacts |
|---|---|---|---|---|---|---|
| Integrated Program for Substance Abuse Research | Baltimore | Maryland | 21205 | United States |
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Of the 65 participants who were consented for the study, 33 were determined to be ineligible during the assessment procedures. Among the 32 persons who were eligible, 16 were not randomized to study medication (8 participants were lost to follow-up and 8 participants withdrew from the study).
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| ID | Title | Description |
|---|---|---|
| FG000 | 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. Mifepristone: Participants receive 6 doses. |
| FG001 | 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. Placebo - Cap: Participants receive 6 doses |
| FG002 | 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. |
| FG003 | Healthy Control - Placebo | Healthy control participants who were randomized to receive placebo. This is an inactive compound which appears physically identical to active medication. |
| Title | Milestones | Reasons Not Completed | ||||||||||||||||||
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Overall Study |
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| ID | Title | Description |
|---|---|---|
| BG000 | 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. |
| BG001 |
| Units | Counts |
|---|---|
| Participants |
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| Title | Description | Population Description | Parameter Type | Dispersion Type | Unit of Measure | Calculate Percentage | Denominator Units Selected | Denominators | Classes |
|---|---|---|---|---|---|---|---|---|---|
| Age, Continuous | Mean |
| Type | Title | Description | Population Description | Reporting Status | Anticipated Posting Date | Parameter Type | Dispersion Type | Unit of Measure | Calculate Percentage | Time Frame | Units Analyzed | Denominator Units Selected | Arm/Group Information | Denominators | Classes | Analyses | |||
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Primary | 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. | No data were collected for the AUD Mifepristone participants. AUD Mifepristone participants either dropped out or were withdrawn from the study prior to fMRI procedures. In addition, fMRI data were lost on one AUD-Placebo participant and one Healthy Control - Placebo participant due to head movement artifact. | Posted | Mean | Standard Error | BOLD response | Change from baseline (Day 1) to day 4 of MIFE dosing |
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Up to 6 weeks post followup
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| ID | Title | Description | Deaths (Affected) | Deaths (At Risk) | Serious Events (Affected) | Serious Events (At Risk) | Other Events (Affected) | Other Events (At Risk) |
|---|---|---|---|---|---|---|---|---|
| EG000 | 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. |
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| Term | Organ System | Source Vocabulary | Assessment Type | Notes | Statistical Information |
|---|---|---|---|---|---|
| Rash | Skin and subcutaneous tissue disorders | Non-systematic Assessment |
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| Title | Organization | Phone | Extension | |
|---|---|---|---|---|
| Mary E McCaul, Ph.D. | Johns Hopkins University School of Medicine | 4437225728 | mmccaul1@jhmi.edu |
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| Type | Includes Protocol | Includes SAP | Includes ICF | Document Label | Document Date | Document Uploaded Date | Document File Name |
|---|---|---|---|---|---|---|---|
| Prot_SAP | Yes | Yes | No | Study Protocol and Statistical Analysis Plan | Mar 17, 2021 | Jan 30, 2025 | Prot_SAP_000.pdf |
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| ID | Term |
|---|---|
| D000437 | Alcoholism |
| ID | Term |
|---|---|
| D019973 | Alcohol-Related Disorders |
| D019966 | Substance-Related Disorders |
| D064419 | Chemically-Induced Disorders |
| D001523 | Mental Disorders |
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| ID | Term |
|---|---|
| D015735 | Mifepristone |
| ID | Term |
|---|---|
| D004963 | Estrenes |
| D004962 | Estranes |
| D013256 | Steroids |
| D000072473 | Fused-Ring Compounds |
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| Placebo - Cap | Drug | Participants receive 6 doses |
|
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 |
| Physician Decision |
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| Withdrawal by Subject |
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| 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. |
| BG002 | 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. |
| BG003 | Healthy Control - Placebo | Healthy control participants who were randomized to receive placebo. This is an inactive compound which appears physically identical to active medication. |
| BG004 | Total | Total of all reporting groups |
| years |
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| Sex: Female, Male | Count of Participants | Participants |
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| Race (NIH/OMB) | Count of Participants | Participants |
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| Region of Enrollment | Count of Participants | Participants |
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| OG001 | 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. |
| OG002 | 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. |
| OG003 | Healthy Control - Placebo | Healthy control participants who were randomized to receive placebo. This is an inactive compound which appears physically identical to active medication. |
|
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| Secondary | Mean of Alcohol Motivated Responses Made | 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. | This measure was designed to only be collected among the participants with alcohol use disorder (AUD). None of the AUD participants randomized to mifepristone completed the study. No data were collected for AUD-Mifepristone participants as they either dropped out or were withdrawn from the study prior to completing this procedure. | Posted | Mean | Standard Deviation | responses made | single session on study day 5 |
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| Secondary | Alcohol Motivated Responding - Number of Drinks Earned | Participants can earn up to 10 drinks during a 1-hr session. Each drink was the equivalent of 0.5 standard drink. | This measure was designed to only be collected among the participants with alcohol use disorder (AUD). None of the AUD participants randomized to mifepristone completed the study. No data were collected for participants in the AUD-Mifepristone group. Participants either dropped out or were withdrawn from the study before completing this procedure. | Posted | Mean | Standard Deviation | drinks earned | single session on study day 5 |
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| 0 |
| 4 |
| 0 |
| 4 |
| 0 |
| 4 |
| EG001 | 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. | 0 | 3 | 0 | 3 | 0 | 3 |
| EG002 | 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. | 0 | 6 | 0 | 6 | 2 | 6 |
| EG003 | Health Control - Placebo | Healthy control participants who were randomized to receive placebo. This is an inactive compound which appears physically identical to active medication. | 0 | 3 | 0 | 3 | 0 | 3 |
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| D011083 |
| Polycyclic Compounds |