A Pilot Study on the Safety and Efficacy of Mifepristone for the Prevention of Relapses of Alcohol Drinking
试验速览
- 阶段
- 1 期
- 状态
- 已完成
- 入组人数
- 32
- 试验地点
- 1
- 主要终点
- Number of Participants Experiencing Adverse Events in the Mifepristone Versus Placebo Group as a Measure of Safety and Tolerability
研究概览
简要总结
The goal of this study is to determine if, under stress, alcohol drinking is reduced using mifepristone
研究设计
- 研究类型
- Interventional
- 分配方式
- Randomized
- 干预模型
- Crossover
- 主要目的
- Basic Science
- 盲法
- Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
入排标准
- 年龄范围
- 21 Years 至 65 Years（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •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
排除标准
- •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
研究组 & 干预措施
Mifepristone
mifepristone 600-mg/day for a week, in a stress-induced condition triggered by a single dose of 32.4-mg of yohimbine
干预措施: Mifepristone 600-mg/day or placebo for a week (Drug)
Sugar pill
matching placebo/day for a week, in a stress-induced condition triggered by a single dose of 32.4-mg of yohimbine
干预措施: Mifepristone 600-mg/day or placebo for a week (Drug)
结局指标
主要结局
Number of Participants Experiencing Adverse Events in the Mifepristone Versus Placebo Group as a Measure of Safety and Tolerability
时间窗: 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.
次要结局
- Drinking Consumption in the Mifepristone Verses Placebo Group(1 day)
- Alcohol Craving Score on the Alcohol Craving Questionnaire in the Mifepristone Versus Placebo Group(1 day)
研究者
Carolina L Haass-Koffler
Research Fellow
Brown University