Prazosin to Reduce Stress-Induced Alcohol/Drug Craving and Relapse
试验速览
- 阶段
- 1 期
- 状态
- 已完成
- 入组人数
- 100
- 试验地点
- 1
- 主要终点
- Percentage of Heavy Drinking Days (HDD%) During the Full Dose Period From Weeks 3-12
研究概览
简要总结
To test the preliminary efficacy of 16.0 mg of Prazosin daily versus placebo in treatment seeking alcohol dependent individuals. This proposal is a laboratory and treatment outcome study to examine the effects of Prazosin on brief exposure to stress, drug cues and neutral situations on alcohol and drug craving, mood and neurobiological reactivity in a sample of cocaine and/or alcohol dependent individuals. Prazosin will be beneficial for reduction in stress and alcohol cue induced craving and related arousal. In a sample of treatment-seeking alcohol dependent men and women, we propose to examine (a) differences in measures of alcohol craving, emotion state, hypothalamic-pituitary-adrenal (HPA) activation, physiological arousal and plasma catecholamine response to stress imagery and to alcohol cue imagery as compared to neutral imagery; (b) reduction in alcohol abstinence symptoms; and (c) improvement in alcohol treatment outcomes as measured by reductions in heavy drinking days, any drinking days, secondarily on drinks/day, anxiety, mood and sleep.
详细描述
This is a proof-of-concept (POC) experimental therapeutics study with 2 arms. The first is a double-blind placebo controlled laboratory study with 40 individuals meeting current alcohol dependence criteria (DSM-IVTR) who are admitted to the Clinical Neuroscience Research Unit and initiated on Prazosin vs Placebo (16mg/day) after admission and initial detoxification (if required). Experimental laboratory sessions are conducted after subjects achieved full dose after the 2-week titration, in week 3-4 of inpatient stay. The laboratory outcomes included alcohol craving, anxiety, negative affect and neuroendocrine and sympathetic arousal measures. Individuals who wished to remain on study medication for the outpatient (Arm 2) were maintained on study medication throughout the outpatient phase for a total period of 12 weeks.
Arm 2 of the POC study is a 12-week randomized clinical trial (RCT) of Prazosin (16mg/day) versus Placebo in 100 treatment seeking alcohol dependent individuals, to assess whether high anxiety and distress, including alcohol craving, manifest as increased alcohol withdrawal symptoms at treatment entry moderates Prazosin effects on alcohol use outcomes. Primary alcohol use outcomes include heavy drinking days, any drinking days and secondarily drinks/day. Additional secondary outcomes include alcohol craving, anxiety and mood symptoms and sleep disturbances. Patients from Arm 1 who wished to continue on study medication for the outpatient phase were included in Arm 2. Arm 2 patients were initiated on study medication upon presenting with a negative breathalyzer without any minimum pre-treatment alcohol abstinence period prior to medication initiation.
研究设计
- 研究类型
- Interventional
- 分配方式
- Randomized
- 干预模型
- Parallel
- 主要目的
- Treatment
- 盲法
- Triple (Participant, Care Provider, Investigator)
盲法说明
Randomization into Prazosin/Placebo treatment was conducted by the Yale Stress Center biostatistician using an Urn randomization procedure that balanced groups on gender, age, nicotine smoking status, education years and lifetime history of DSM-IVTR anxiety disorders, including Post Traumatic Stress Disorder (PTSD). Random assignment of each patient was provided to the Yale Investigational Drug Service (IDS) Pharmacist, who formulated identical, matched tablets of Prazosin and Placebo, and provided dosing in weekly blister packs labeled by day and time of dosing for each subject to study staff for dispensing. All study personnel, including investigators, physicians, study staff and patients remained blind to medication group.
入排标准
- 年龄范围
- 18 Years 至 70 Years（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •Male or female individuals, ages 18-70 with alcohol dependence, treatment seeking with varying levels of alcohol withdrawal symptoms.
- •meet current DSM-IV criteria for alcohol dependence,
- •Subject has voluntarily given informed consent and signed the informed consent document.
- •Able to read English and complete study evaluations.
排除标准
- •Meet current criteria for dependence on another psychoactive substance, excluding nicotine and caffeine;
- •Any current use of opiates;
- •Current use of any psychoactive drugs, including anxiolytics, antidepressants, naltrexone or disulfram, except for stabilized on SSRIs
- •Any psychotic disorder or current Axis I psychiatric symptoms requiring specific attention, including need for psychiatric medications for current major depression and anxiety disorders
- •Significant underlying medical conditions such as cerebral, renal, thyroid or cardiac pathology which in the opinion of study physician would preclude patient from fully cooperating or be of potential harm during the course of the study;
- •Hypotensive individuals with sitting blood pressure below 90/60 mmHG.
研究组 & 干预措施
High Alcohol Withdrawal on Prazosin
High AW was determined by those scoring at or above the median on Clinical Institute of Withdrawal for Alcohol Revised (CIWA-Ar) assessment. High AW were randomized to Prazosin 16 mg/day (tid) administered for 12 weeks with fish-bowl contingency management for weekly treatment attendance and manualized 12-Step relapse prevention counseling in a double blind manner.
干预措施: Prazosin Tablet (Drug)
High Alcohol Withdrawal on PLA
High AW was determined by those scoring at or above the median on Clinical Institute of Withdrawal for Alcohol Revised (CIWA-Ar) assessment. High AW were randomized to Placebo tablets administered tid for 12 weeks with fish-bowl contingency management for weekly treatment attendance and manualized 12-Step relapse prevention counseling in a double blind manner.
干预措施: Placebo Tablet (Drug)
Low Alcohol Withdrawal on Prazosin
Low AW was determined by those scoring below the median on Clinical Institute of Withdrawal for Alcohol Revised (CIWA-Ar) assessment. Low AW were randomized to Prazosin 16 mg/day (tid) administered for 12 weeks with fish-bowl contingency management for weekly treatment attendance and manualized 12-Step relapse prevention counseling in a double blind manner.
干预措施: Prazosin Tablet (Drug)
Low Alcohol Withdrawal on PLA
Low AW was determined by those scoring below the median on Clinical Institute of Withdrawal for Alcohol Revised (CIWA-Ar) assessment.Placebo tablets administered tid for 12 weeks with fish-bowl contingency management for weekly treatment attendance and manualized 12-Step relapse prevention counseling in a double blind manner.
干预措施: Placebo Tablet (Drug)
结局指标
主要结局
Percentage of Heavy Drinking Days (HDD%) During the Full Dose Period From Weeks 3-12
时间窗: daily over 12 weeks
Percentage of heavy drinking days (HDD%) during the full dose period from weeks 3-12 where heavy drinking day (HDD) is defined as 5 or more for men and 4 or more for women in one sitting, measured as yes (1) or no(0), assessed via self reports by daily surveys and time-line follow back assessments
Percent of Drinkings Days During the Full Dose Period Between Weeks 3 and 12
时间窗: daily over 12 weeks
Percent of any drinkings days over the full dose period from weeks 3 to 12, defined as any alcoholic drink consumed each day measured as yes (1) or no(0), assessed via self reports by daily surveys and time-line follow back assessments
次要结局
未报告次要终点