Mifepristone for the Prevention of Relapses of Alcohol Drinking

Phase 1

Completed

Conditions: Alcohol Use Disorders (AUD)

Interventions: Drug: Mifepristone 600-mg/day or placebo for a week

Registration Number: NCT02243709

Lead Sponsor: Brown University

Brief Summary: The goal of this study is to determine if, under stress, alcohol drinking is reduced using mifepristone

Detailed Description: Not available

Recruitment & Eligibility

Status: COMPLETED

Sex: All

Target Recruitment: 32

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

Study & Design

Study Type: INTERVENTIONAL

Study Design: CROSSOVER

Arm && Interventions

Group	Intervention	Description
Sugar pill	Mifepristone 600-mg/day or placebo for a week	matching placebo/day for a week, in a stress-induced condition triggered by a single dose of 32.4-mg of yohimbine
Mifepristone	Mifepristone 600-mg/day or placebo for a week	mifepristone 600-mg/day for a week, in a stress-induced condition triggered by a single dose of 32.4-mg of yohimbine

Primary Outcome Measures

Name	Time	Method
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 Outcome Measures

Name	Time	Method
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.
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.