Orexin Receptor Antagonists as Modulators of Threat Sensitivity in Individuals With Alcohol Use Disorder
试验速览
- 阶段
- 早期 1 期
- 状态
- 已完成
- 入组人数
- 81
- 试验地点
- 1
- 主要终点
- Percentage of Heavy Drinking Days During Daily Use of Suvorexant.
研究概览
简要总结
The goal of this double-blind clinical trial is to further explore if, how, and for whom orexin antagonism modifies brain-behavior stress targets in moderate to severe alcohol use disorder (AUD). The main questions it aims to answer are:
- Does an acute dose of suvorexant (SUV) and/or daily use of SUV modify brain-behavior targets of AUD dysfunction?
- Does daily SUV use change alcohol behavior and if so, is this change in behavior linked to brain-behavior change?
Participants will be randomized to a treatment group (SUV or placebo) and protocol arm, electromyography (EMG) only or EMG+functional magnetic resonance imaging (fMRI). Participants will be asked to complete the following:
- Baseline lab visit(s) that include the psychophysiological stress paradigm (EMG only or EMG+fMRI, dependent upon randomization).
- Acute drug challenge where the participant will return to the lab to repeat the stress paradigm following administration of a single dose of either 10mg SUV or placebo.
- Medication trial where participants will be instructed to take 10mg capsules of SUV or placebo orally each night before bedtime for 4-weeks.
- Daily reports of medication adherence, side-effects, sleep, alcohol use, and mood will be collected via smartphones during the 4-week medication trial.
- Post-treatment lab visit(s) where participants will return to the lab at the end of the medication trial and complete the same stress paradigm from baseline (EMG only or EMG+fMRI, dependent upon randomization).
研究设计
- 研究类型
- Interventional
- 分配方式
- Randomized
- 干预模型
- Parallel
- 主要目的
- Basic Science
- 盲法
- Double (Participant, Outcomes Assessor)
入排标准
- 年龄范围
- 18 Years 至 65 Years（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •Participant is able to give informed consent.
- •Generally medically and physically healthy as confirmed by medical history.
- •Meet DSM-5 diagnostic criteria for current moderate or severe AUD.
- •Engage in heavy alcohol use defined as drinking equal or greater than 14 standard drinks per week if male and equal or greater than 7 standard drinks per week if female.
排除标准
- •Clinically significant medical or neurological condition (e.g., liver disease, narcolepsy, complex sleep behaviors, severe hepatic impairment, COPD, severe obstructive sleep apnea).
- •Current cognitive dysfunction (traumatic brain injury, mental retardation, organic mental syndrome, pervasive developmental disorder, or dementia).
- •Current use of antihistamines, strong or moderate inhibitors of CYP3A liver enzymes, strong CYP3A inducers, or digoxin.
- •Current or past DSM-5 diagnosis of mania, schizophrenia, psychosis, suicidality, major depressive disorder, or obsessive compulsive disorder.
- •Current substance use disorder other than alcohol or mild cannabis use disorder.
- •Treatment seeking for AUD.
- •Recent psychotropic medication use in the past 2 months.
- •Currently smokes 5 or more cigarettes (or electronic equivalent) per day.
- •BMI equal or greater than
- •Engage in night-shift work.
- •Lack of fluency in English.
- •Presence of ferrous-containing metal in the body.
- •Inability to tolerate small, enclosed spaces.
- •Deafness in one or both ears.
- •Currently pregnant (positive pregnancy test), lactating, or not agreeing to use birth control methods during the duration of the trial.
研究组 & 干预措施
Control
Individuals will take a placebo pill during the Acute Drug Challenge and daily for 28 days.
干预措施: Placebo (Other)
Suvorexant Treatment
Individuals will take 10mg of suvorexant (Merck & Co Inc.) during the Acute Drug Challenge and daily for 28 days.
干预措施: Suvorexant (Drug)
结局指标
主要结局
Percentage of Heavy Drinking Days During Daily Use of Suvorexant.
时间窗: Change from baseline to post-treatment, over the course of 4 weeks.
Percentage of heavy drinking days (PHDD) was calculated each week for all four weeks of the trial. A heavy drinking day was defined using NIH criteria: 5+ drinks for males and 4+ drinks for females in a single day. We conducted a multilevel mixed model with PHDD from week 1 to 4 as the within-subjects variable and treatment arm as the between subjects variable.
Startle Eyeblink Electromyographic (EMG) Response to Stress With an Acute Dose of Suvorexant
时间窗: Change from baseline to 2 hours post-ingestion of an acute dose of suvorexant.
Startle EMG responses were collected during the well-validated No-Predictable-Unpredictable threat paradigm. The task includes within-subjects conditions and raw EMG responses were averaged for each condition. To quantify the difference between threat and no-threat periods, we calculated a standardized residual score for unpredictable threat (U-threat) by saving the variance leftover (i.e., the amount of variability in a dependent variable \[DV\] that is not explained by an independent variable \[IV\]) in a simple linear regression, where the no-threat EMG startle average (IV) was entered to predict the U-threat EMG startle average (DV). The U-threat residual score was used as the primary variable. It has a mean of zero and higher scores reflect greater startle reactivity to U-threat. U-threat residual scores were calculated for the baseline session and the acute challenge.
Startle Eyeblink Electromyographic (EMG) Response to Stress With Daily Use of Suvorexant.
时间窗: Change from baseline to post-treatment, up to 2 months.
Startle EMG responses were collected during the well-validated No-Predictable-Unpredictable threat paradigm. The task includes within-subjects conditions and raw EMG responses were averaged for each condition. To quantify the difference between threat and no-threat periods, we calculated a standardized residual score for unpredictable threat (U-threat) by saving the variance leftover (i.e., the amount of variability in a dependent variable \[DV\] that is not explained by an independent variable \[IV\]) in a simple linear regression, where the no-threat EMG startle average (IV) was entered to predict the U-threat EMG startle average (DV). The U-threat residual score was used as the primary variable. It has a mean of zero and higher scores reflect greater startle reactivity to U-threat.
次要结局
- Changes in Neural Activation During Unpredictable Stress Anticipation Following Daily Use of Suvorexant.(Change from baseline to post-treatment, up to 2 months.)
研究者
Stephanie M Gorka, PhD
Associate Professor
Ohio State University