Alcohol Use Disorders (AUD)
Conditions
Keywords
Stress, alcohol craving, alcohol use disorders
Brief summary
The goal of this study is to determine if, under stress, alcohol drinking is reduced using mifepristone
Interventions
DRUGMifepristone 600-mg/day or placebo for a week
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
Sponsors
Brown University
Study design
Allocation
RANDOMIZED
Intervention model
CROSSOVER
Primary purpose
BASIC_SCIENCE
Masking
QUADRUPLE (Subject, Caregiver, Investigator, Outcomes Assessor)
Eligibility
Sex/Gender
ALL
Age
21 Years to 65 Years
Healthy volunteers
No
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
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Number of Participants Experiencing Adverse Events in the Mifepristone Versus Placebo Group as a Measure of Safety and Tolerability | 5 weeks (one week of drug administration, 3 weeks of washout, followed by one week of drug administration) | 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
| Measure | Time frame | Description |
|---|---|---|
| Alcohol Craving Score on the Alcohol Craving Questionnaire in the Mifepristone Versus Placebo Group | 1 day | 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 | 1 day | 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. |
Countries
United States
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| Overall Sample All participants receive either Mifepristone (600 mg) or matched placebo that is randomized within a cross-over, double blind clinical trial. | 32 |
| Total | 32 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 |
|---|---|---|---|
| Phase 1 | Adverse Event | 0 | 1 |
| Phase 1 | Lost to Follow-up | 0 | 1 |
| Phase 1 | Protocol Violation | 0 | 1 |
| Phase 1 | Withdrawal by Subject | 1 | 0 |
Baseline characteristics
| Characteristic | Overall Sample |
|---|---|
| Age, Continuous | 42.9 years STANDARD_DEVIATION 11.8 |
| Alcohol craving | 40.9 units on a scale STANDARD_DEVIATION 14.8 |
| Race/Ethnicity, Customized African American | 9 Participants |
| Race/Ethnicity, Customized Multiracial | 1 Participants |
| Race/Ethnicity, Customized WHITE | 22 Participants |
| Region of Enrollment United States | 32 Participants |
| Sex: Female, Male Female | 5 Participants |
| Sex: Female, Male Male | 27 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | 0 / 27 | 0 / 31 |
| other Total, other adverse events | 0 / 27 | 3 / 31 |
| serious Total, serious adverse events | 0 / 27 | 0 / 31 |
Outcome results
Primary
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.
Time frame: 5 weeks (one week of drug administration, 3 weeks of washout, followed by one week of drug administration)
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Mifepristone | Number of Participants Experiencing Adverse Events in the Mifepristone Versus Placebo Group as a Measure of Safety and Tolerability | 0 Participants |
| Placebo | Number of Participants Experiencing Adverse Events in the Mifepristone Versus Placebo Group as a Measure of Safety and Tolerability | 3 Participants |
p-value: >0.05Chi-squared
Secondary
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.
Time frame: 1 day
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Mifepristone | Alcohol Craving Score on the Alcohol Craving Questionnaire in the Mifepristone Versus Placebo Group | 42.92 score on a scale | Standard Deviation 17.85 |
| Placebo | Alcohol Craving Score on the Alcohol Craving Questionnaire in the Mifepristone Versus Placebo Group | 50.13 score on a scale | Standard Deviation 19.3 |
Secondary
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.
Time frame: 1 day
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Mifepristone | Drinking Consumption in the Mifepristone Verses Placebo Group | 0.8 drinks | Standard Error 0.3 |
| Placebo | Drinking Consumption in the Mifepristone Verses Placebo Group | 0.5 drinks | Standard Error 0.2 |