Back to resultsMifepristone for the Prevention of Relapses of Alcohol Drinking
Primary Purpose
Alcohol Use Disorders (AUD)
Status
Completed
Phase
Phase 1
Locations
United States
Study Type
Interventional
Intervention
Mifepristone 600-mg/day or placebo for a week
Sponsored by
About this trial
This is an interventional basic science trial for Alcohol Use Disorders (AUD) focused on measuring Stress, alcohol craving, alcohol use disorders
Eligibility Criteria
Inclusion Criteria:
- Male or female, 21 to 65 years of age
- Females must be postmenopausal for at least one year or surgically sterile (proven by medical record)
- Meet criteria for Alcohol Use Disorders (AUD) DSM-5 diagnosis
- Meet drinking criteria (≥3 drinks/day for men; ≥2 drinks /day for women)
- Must be in good health as confirmed by medical history, physical examination, ECG, lab tests
- Participants must be willing to take oral medication and adhere to the study procedures
- Breath alcohol (BrAC) = 0.00 at each visit
- Be able to understand informed consent and questionnaire in English at an 8th grade level
Exclusion Criteria:
- Individuals expressing interest in treatment for alcoholism
- Premenopausal women
- Participants who have significant alcohol withdrawal symptoms, defined as a CIWA-Ar score ≥7
- A repeated positive urine drug screen at baseline for any illegal substance except marijuana.
- Individuals diagnosed with a current "severe" Substance Use Disorder (SUD) diagnosis, other than alcohol or nicotine
- Meet DSM-5 criteria for a diagnosis of schizophrenia, bipolar disorder, or other psychoses
- An active illness within the past six months of the screening visit that meets the DSM-5 criteria for a diagnosis of Major Depressive Disorder (MDD) or Anxiety Disorder, or history of attempted suicide
- Clinically significant medical abnormalities: unstable hypertension, clinically significant abnormal ECG, bilirubin >150% of the upper normal limit, ALT/AST >300% the UNL, creatinine clearance ≤60 dl/min
- Current use of psychotropic medications that may have an effect on alcohol consumption
- Current use of any medication involved in the metabolism of alcohol such as aldehyde dehydrogenase (ALDH), alcohol dehydrogenase (ADH) and CYP2E1: Cefamandole, Cefotetan, Sulfamethoxazole, Nitroglycerin, Chlorpropamide, Glyburide.
- Current use of any medication (CYP3A4 inhibitor and substrate) that may interact with mifepristone: cyclosporine, fentanyl, heparin, escitalopram, lovastatin, simvastatin, warfarin
- Current use of any medication (CYP2D6 inhibitor and substrate) that may interact with yohimbine: amitriptyline, doxepin, nortriptyline, venlafaxine
- Medical contraindications for use of mifepristone or yohimbine
- A history of adverse reaction or hypersensitivity to mifepristone or yohimbine
- History of suicide
- History of seizure disorders
- Hypokalemia (low potassium level)<3.5mEq/L
- Participated in any behavioral and/or pharmacological study within minimum the past 30 days
- Neuroendocrine disorders
- Taking corticosteroids
- Bleeding disorders
- Pre-existing QT prolongation on ECG
- History of porphyria (Mifepristone progesterone receptor antagonist is an inducer of CYP-450 and therefore may have the ability to precipitate or exacerbate attacks of acute porphyria)
- Not willing to engage in protected sex (condom). This risk includes both women and men. Mifepristone long half-life (t1/2 = 18 hrs) and its three main metabolites retain considerable affinity toward human progesterone and glucocorticoid receptors, with serum level similar to the parent mifepristone and there are no studies on the presence of mifepristone or metabolites in semen
Sites / Locations
- Center for Alcohol and Addiction Studies, Brown University
Arms of the Study
Arm 1
Arm 2
Arm Type
Active Comparator
Placebo Comparator
Arm Label
Mifepristone
Sugar pill
Arm Description
mifepristone 600-mg/day for a week, in a stress-induced condition triggered by a single dose of 32.4-mg of yohimbine
matching placebo/day for a week, in a stress-induced condition triggered by a single dose of 32.4-mg of yohimbine
Outcomes
Primary Outcome Measures
Number of Participants Experiencing Adverse Events in the Mifepristone Versus Placebo Group as a Measure of Safety and Tolerability
Safety and tolerability was assessed by the number of participants who experienced adverse events (AEs) while taking the medication, in the mifepristone group verses the placebo group during Visit 2 through and until Visit 5. AEs were assessed at each visit and special attention was paid to any AEs experienced after administration of the oral administration of mifepristone or placebo- Visit 2 to Visit 3 (7 days total) and Visit 4 through Visit 5 (7 days total), and when it was administered with alcohol during the laboratory paradigms at visits 3 and 4.
Secondary Outcome Measures
Alcohol Craving Score on the Alcohol Craving Questionnaire in the Mifepristone Versus Placebo Group
Alcohol craving will be assessed by the Alcohol Craving Questionnaire Short Form - Revised (ACQ-SF-R). The ACQ-SF-R is a 12-item self-report scale that contains items from the 47-item Alcohol Craving Questionnaire (ACQ-Now). ACQ-SF-R also produces scores for compulsivity, expectancy, purposefulness, and emotionality. To assess this outcome, at the alcohol cue reactivity procedures/visits 3 and 5 during alcohol trial 1, the 12-item total ACQ will be summed for each participant and then the total score will be averaged for a mean score. The average ACQ score in the presence of alcohol cues will be compared when participants are taking mifepristone compared to placebo. The ACQ has a total score range between 0-84. A lower score indicates less subjective alcohol craving.
Drinking Consumption in the Mifepristone Verses Placebo Group
Number of standard drinks desired to be consumed by participants during mifepristone administration compared to placebo administration during the open bar (free choice procedure) in the alcohol cue reactivity at visits 3 and 5.
Full Information
1. Study Identification
Unique Protocol Identification Number
NCT02243709
Brief Title
Mifepristone for the Prevention of Relapses of Alcohol Drinking
Official Title
A Pilot Study on the Safety and Efficacy of Mifepristone for the Prevention of Relapses of Alcohol Drinking
Study Type
Interventional
2. Study Status
Record Verification Date
May 2023
Overall Recruitment Status
Completed
Study Start Date
September 2014 (Actual)
Primary Completion Date
December 21, 2021 (Actual)
Study Completion Date
December 21, 2021 (Actual)
3. Sponsor/Collaborators
Responsible Party, by Official Title
Principal Investigator
Name of the Sponsor
Brown University
4. Oversight
Data Monitoring Committee
No
5. Study Description
Brief Summary
The goal of this study is to determine if, under stress, alcohol drinking is reduced using mifepristone
6. Conditions and Keywords
Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Alcohol Use Disorders (AUD)
Keywords
Stress, alcohol craving, alcohol use disorders
7. Study Design
Primary Purpose
Basic Science
Study Phase
Phase 1, Phase 2
Interventional Study Model
Crossover Assignment
Masking
ParticipantCare ProviderInvestigatorOutcomes Assessor
Allocation
Randomized
Enrollment
32 (Actual)
8. Arms, Groups, and Interventions
Arm Title
Mifepristone
Arm Type
Active Comparator
Arm Description
mifepristone 600-mg/day for a week, in a stress-induced condition triggered by a single dose of 32.4-mg of yohimbine
Arm Title
Sugar pill
Arm Type
Placebo Comparator
Arm Description
matching placebo/day for a week, in a stress-induced condition triggered by a single dose of 32.4-mg of yohimbine
Intervention Type
Drug
Intervention Name(s)
Mifepristone 600-mg/day or placebo for a week
Intervention Description
600-mg of mifepristone for a week, compared to placebo for a week, in a stress-induced condition triggered by a single dose of 32.4 mg of yohimbine
Primary Outcome Measure Information:
Title
Number of Participants Experiencing Adverse Events in the Mifepristone Versus Placebo Group as a Measure of Safety and Tolerability
Description
Safety and tolerability was assessed by the number of participants who experienced adverse events (AEs) while taking the medication, in the mifepristone group verses the placebo group during Visit 2 through and until Visit 5. AEs were assessed at each visit and special attention was paid to any AEs experienced after administration of the oral administration of mifepristone or placebo- Visit 2 to Visit 3 (7 days total) and Visit 4 through Visit 5 (7 days total), and when it was administered with alcohol during the laboratory paradigms at visits 3 and 4.
Time Frame
5 weeks (one week of drug administration, 3 weeks of washout, followed by one week of drug administration)
Secondary Outcome Measure Information:
Title
Alcohol Craving Score on the Alcohol Craving Questionnaire in the Mifepristone Versus Placebo Group
Description
Alcohol craving will be assessed by the Alcohol Craving Questionnaire Short Form - Revised (ACQ-SF-R). The ACQ-SF-R is a 12-item self-report scale that contains items from the 47-item Alcohol Craving Questionnaire (ACQ-Now). ACQ-SF-R also produces scores for compulsivity, expectancy, purposefulness, and emotionality. To assess this outcome, at the alcohol cue reactivity procedures/visits 3 and 5 during alcohol trial 1, the 12-item total ACQ will be summed for each participant and then the total score will be averaged for a mean score. The average ACQ score in the presence of alcohol cues will be compared when participants are taking mifepristone compared to placebo. The ACQ has a total score range between 0-84. A lower score indicates less subjective alcohol craving.
Time Frame
1 day
Title
Drinking Consumption in the Mifepristone Verses Placebo Group
Description
Number of standard drinks desired to be consumed by participants during mifepristone administration compared to placebo administration during the open bar (free choice procedure) in the alcohol cue reactivity at visits 3 and 5.
Time Frame
1 day
10. Eligibility
Sex
All
Minimum Age & Unit of Time
21 Years
Maximum Age & Unit of Time
65 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
Inclusion Criteria:
Male or female, 21 to 65 years of age
Females must be postmenopausal for at least one year or surgically sterile (proven by medical record)
Meet criteria for Alcohol Use Disorders (AUD) DSM-5 diagnosis
Meet drinking criteria (≥3 drinks/day for men; ≥2 drinks /day for women)
Must be in good health as confirmed by medical history, physical examination, ECG, lab tests
Participants must be willing to take oral medication and adhere to the study procedures
Breath alcohol (BrAC) = 0.00 at each visit
Be able to understand informed consent and questionnaire in English at an 8th grade level
Exclusion Criteria:
Individuals expressing interest in treatment for alcoholism
Premenopausal women
Participants who have significant alcohol withdrawal symptoms, defined as a CIWA-Ar score ≥7
A repeated positive urine drug screen at baseline for any illegal substance except marijuana.
Individuals diagnosed with a current "severe" Substance Use Disorder (SUD) diagnosis, other than alcohol or nicotine
Meet DSM-5 criteria for a diagnosis of schizophrenia, bipolar disorder, or other psychoses
An active illness within the past six months of the screening visit that meets the DSM-5 criteria for a diagnosis of Major Depressive Disorder (MDD) or Anxiety Disorder, or history of attempted suicide
Clinically significant medical abnormalities: unstable hypertension, clinically significant abnormal ECG, bilirubin >150% of the upper normal limit, ALT/AST >300% the UNL, creatinine clearance ≤60 dl/min
Current use of psychotropic medications that may have an effect on alcohol consumption
Current use of any medication involved in the metabolism of alcohol such as aldehyde dehydrogenase (ALDH), alcohol dehydrogenase (ADH) and CYP2E1: Cefamandole, Cefotetan, Sulfamethoxazole, Nitroglycerin, Chlorpropamide, Glyburide.
Current use of any medication (CYP3A4 inhibitor and substrate) that may interact with mifepristone: cyclosporine, fentanyl, heparin, escitalopram, lovastatin, simvastatin, warfarin
Current use of any medication (CYP2D6 inhibitor and substrate) that may interact with yohimbine: amitriptyline, doxepin, nortriptyline, venlafaxine
Medical contraindications for use of mifepristone or yohimbine
A history of adverse reaction or hypersensitivity to mifepristone or yohimbine
History of suicide
History of seizure disorders
Hypokalemia (low potassium level)<3.5mEq/L
Participated in any behavioral and/or pharmacological study within minimum the past 30 days
Neuroendocrine disorders
Taking corticosteroids
Bleeding disorders
Pre-existing QT prolongation on ECG
History of porphyria (Mifepristone progesterone receptor antagonist is an inducer of CYP-450 and therefore may have the ability to precipitate or exacerbate attacks of acute porphyria)
Not willing to engage in protected sex (condom). This risk includes both women and men. Mifepristone long half-life (t1/2 = 18 hrs) and its three main metabolites retain considerable affinity toward human progesterone and glucocorticoid receptors, with serum level similar to the parent mifepristone and there are no studies on the presence of mifepristone or metabolites in semen
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Carolina L Haass-Koffler, PharmD
Organizational Affiliation
Brown University
Official's Role
Principal Investigator
Facility Information:
Facility Name
Center for Alcohol and Addiction Studies, Brown University
City
Providence
State/Province
Rhode Island
ZIP/Postal Code
02912
Country
United States
12. IPD Sharing Statement
Citations:
PubMed Identifier
22048462
Citation
Simms JA, Haass-Koffler CL, Bito-Onon J, Li R, Bartlett SE. Mifepristone in the central nucleus of the amygdala reduces yohimbine stress-induced reinstatement of ethanol-seeking. Neuropsychopharmacology. 2012 Mar;37(4):906-18. doi: 10.1038/npp.2011.268. Epub 2011 Nov 2.
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Mifepristone for the Prevention of Relapses of Alcohol Drinking
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