Subjective and Physiological Effects of Alcohol: Role of Genetic Variation and Adrenal Hormones
试验速览
- 阶段
- 不适用
- 状态
- 已完成
- 发起方
- 入组人数
- 94
- 试验地点
- 1
- 主要终点
- Breath Alcohol
研究概览
简要总结
This study will explore the hypothesis that effects of alcohol are in part mediated by increased production of neuroactive steroids, which interact with GABAA-receptors. We propose to study non-dependent drinkers using a 4-session within-subjects design in which alcohol / placebo is paired with dutasteride / placebo pretreatment. Dutasteride is a 5-alpha steroid reductase (5AR) inhibitor that limits the production of dihydrotestosterone and the 5a-reduced neuroactive steroids allopregnanolone, pregnanolone and 3a,5a-androstanediol.
详细描述
Alcohol has multiple pharmacological effects, though which of these effects relate to the risk of alcohol dependence is not clear. Animal studies indicate that the neuroactive steroid allopregnanolone is an alcohol-modulated endogenous agonist at GABAA receptors and that genetic variation in steroid 5a-reductase type I gene which generates neuroactive steroids, may moderate alcohol effects. To better define the role of neuroactive steroids we will conduct a laboratory study of non-alcohol dependent drinkers using a 4-session design in which alcohol/placebo beverage is paired with dutasteride/placebo pretreatment. Dutasteride, an inhibitor of both type I and type II 5a-reductase enzymes, blocks the production of 5a-reduced neuroactive steroids. This study will extend our preliminary findings with finasteride by including a) a placebo control for alcohol, b) a more specific inhibitor of both 5a-reductase isoenzymes, c) a larger group of subjects (including both light and heavy drinkers).
研究设计
- 研究类型
- Interventional
- 分配方式
- Randomized
- 干预模型
- Factorial
- 盲法
- Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
入排标准
- 年龄范围
- 21 Years 至 45 Years（Adult）
- 性别
- Male
- 接受健康志愿者
- 是
入选标准
- •Main Study: Subjects will be healthy volunteers with or without parental history of alcoholism who are 21-45 years old and who have a BMI >18.5 and <32.
- •Drinking history: All subjects must report at least one occasion in the prior month of drinking at least 3 drinks on a single day; additionally, LD subjects will be selected if they drink 1-3 drinks, 1-3 times per week (up to 5 drinks per week on average), with no more than one occasion in the past 2 months on which they drank >4 drinks. HD subjects will be selected if they report drinking at least 10 drinks per week, with at least one episode per week of heavy drinking.
排除标准
- •Main Study: Subjects cannot have a current or past DSM-IV diagnosis of alcohol or drug dependence, current or past 24-months diagnosis of alcohol or drug abuse or another major psychiatric disorder, neurological illness, have had a hypersensitivity reaction to dutasteride, evidence of liver dysfunction, currently be using benzodiazepines, other psychotropic medications or medications that are known to influence steroid hormone levels or metabolism or modify the effects of alcohol. Nicotine-dependent subjects will be excluded to avoid the confounding effects of nicotine withdrawal during day-long laboratory sessions. Women are not allowed to participate. Subjects anticipating moving from the area during the period of their planned study participation will be excluded from study entry.
研究组 & 干预措施
Placebo medication + placebo alcohol
干预措施: placebo medication + placebo alcohol (Drug)
Placebo Medication + 0.8 gr/kg Ethanol
干预措施: placebo medication + ethanol (Drug)
4 mg Dutasteride + Placebo Alcohol
干预措施: dutasteride + placebo alcohol (Drug)
4 mg Dutasteride + 0.8 gr/kg Ethanol
干预措施: dutasteride + ethanol (Drug)
结局指标
主要结局
Breath Alcohol
时间窗: 40 minutes after beginning drink
Breath Alcohol level
BAES Sedation Response, Average of 6 Time Points
时间窗: 40, 80, 120, 160, 210 and 240 minutes after start of drinking
Biphasic Alcohol Effects Scale (BAES) Sedation items - sum of subjective responses - 0(not at all)to 10 (extremely)- for 7 sedation related questions regarding effects of alcohol. Total BAES sedation subscale score 0-70 with higher numbers indicating greater sedative effects of alcohol. \[Martin, C. S., M. Earleywine, R. E. Musty, M. W. Perrine and R. M. Swift (1993a). Development and validation of the Biphasic Alcohol Effects Scale. Alcohol Clin Exp Res 17(1): 140-6.\]
BAES Stimulation Response, Average of 6 Time Points
时间窗: 40, 80, 120, 160, 210 and 240 minutes after start of drinking
Biphasic Alcohol Effects Scale (BAES)Simulation items - sum of subjective responses - 0(not at all)to 10 (extremely)- for 7 stimulation related questions regarding effects of alcohol. Total BAES stimulation subscale score 0-70 with higher numbers indicating greater stimulating effects of alcohol. \[Martin, C. S., M. Earleywine, R. E. Musty, M. W. Perrine and R. M. Swift (1993a). Development and validation of the Biphasic Alcohol Effects Scale. Alcohol Clin Exp Res 17(1): 140-6.\]
次要结局
- Change in Serum 3a-androstanediol Glucuronide(Baseline (pre medication administration) and 2-4 days post-medication (alcohol session))
研究者
Jonathan Covault
Associate Professor
UConn Health