Impact of Daridorexant on Sleep, Daytime Alertness, and Smoking During Abstinence
试验速览
- 阶段
- 4 期
- 状态
- 尚未招募
- 入组人数
- 44
- 试验地点
- 1
- 主要终点
- Sleep Quality
研究概览
简要总结
Tobacco use is the leading cause of preventable death in the U.S., with 480,000 deaths per year and 7.7 million deaths globally. A major clinical symptom associated with abstinence from both licit and illicit drugs is insomnia, which is a clinically verified, major risk factor for relapse. Roughly half of the 40 million smokers in the U.S. attempt to quit annually, with very low rates of success. One major hurdle is poor sleep quality during abstinence. Compounding the problem is that some pharmaceuticals to help reduce smoking can increase insomnia. Poor sleep is recognized as a major impediment to maintaining abstinence from several drugs of abuse, including nicotine. Blockers of orexin have recently been proposed as a promising therapy for smoking cessation. Insomnia has been reported in up to 40% of smokers, and 80% report regular sleep disturbances, which can be amplified during abstinence. A new orexin blocker, daridorexant, was FDA approved within the past two years for the treatment of insomnia, and while it has been tested in healthy individuals with insomnia, it has not been tested in smokers, who suffer from insomnia, particularly during the withdrawal phase when trying to quit. Daridorexant has an improved profile of beneficial effects for those with insomnia, the most notable advantage being its shorter duration of action that promotes daytime alertness, which is problematic for both active smokers and smokers during withdrawal. Poor sleep leads to daytime sleepiness, which often leads to smoking to maintain alertness.
详细描述
The investigators will use a randomized, double-blind placebo-controlled design to determine how daridorexant given over 3 weeks of smoking abstinence will alter sleep, daytime alertness, and smoking behavior and craving for cigarettes. Sleep will be monitored using a sleep-tracking device, a sleep diary, and daytime alertness will be monitored using a performance metric (psychomotor vigilance task) three times per week for the 3 week study. Participants will also complete several other questionnaires related to smoking behaviors, craving, withdrawal, daytime sleepiness, and mood.
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
- Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
盲法说明
Medical Monitor will remain blinded unless adverse event.
入排标准
- 年龄范围
- 18 Years 至 55 Years（Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •Adult participants who are cigarette smokers, 18-55 years of age.
- •Smokers: greater than 10 cigarettes/day.
- •Smoking for 1 year or longer.
- •Willingness to try to reduce or stay abstinent from cigarettes, smoking cessation aides (including nicotine gum or patches), smokeless tobacco, or electronic cigarettes for 3 weeks during the study.
- •Willingness to monitor sleep at home with an external device and maintain a simple sleep and smoking diary for 3 weeks.
- •Willingness to take a 5-min, mobile-based test 3X/day for 3 days/week during the 3 weeks.
- •Ability to travel to three Study Visits.
- •Are willing to abstain from consuming grapefruit products during the study.
- •Have an iPhone, best with iOS 17 or newer.
排除标准
- •Are currently taking any pharmaceutical drugs for smoking cessation, including: Nicotine patch or nicotine gum, buproprion (Wellbutrin, Zyban), varenicline (Chantix, Champix), other behavioral interventions such as cognitive behavioral therapy for smoking.
- •Are currently using cannabis or alcohol for sleep. Are currently taking any pharmaceutical drugs for insomnia, such as eszopiclone (Lunesta), zaleplon (Sonata) or zolpidem (Ambien, Ambien CR, Edluar, and Zolpimist) benzodiazepines, or opioids.
- •Are currently taking stimulants commonly used for ADHD, such as methylphenidate (Ritalin Concerta, Daytrana) or amphetamines (Adderall, Dexedrine, Vyvanse).
- •Are currently taking anti-seizure drugs, including lamotrigine, pregabalin (Lyrica), or gabapentin (Neurontin, Horizant, or Gralise).
- •Have non-nicotine substance dependence (diagnosed with substance use disorder, including alcohol or cannabis use disorder (current cannabis use is acceptable, and past illicit drug use is acceptable if greater than 2 months prior to testing and does not meet current criteria for substance use disorders (SUDs) according to DSM-5).
- •Have a major neurological disorder such as Parkinson's disease, epilepsy, Alzheimer's disease, multiple sclerosis, or any other serious neurological disorder.
- •Have a history of serious psychiatric disorders including bipolar disorder, schizophrenia, or suicidality.
- •Had a stroke or head injury which caused loss of consciousness for longer than three minutes in the past 1 year.
- •Are pregnant or breastfeeding.
- •Have been diagnosed with sleep apnea or other diagnosed sleep disorders such as narcolepsy.
- •Have been diagnosed with thyroid problems.
- •Have been diagnosed with COPD.
- •Have been doing variable shift work in the past 1 month or traveled more than 1 time zone in past month.
- •Are currently taking the following medications, supplements, or food: Daridorexant can interact with strong inhibitors of CYP3A4, which should be discussed with The Study Doctor's office (some of these include clarithromycin, diltiazem, erythromycin, itraconzale, ketoconazole, ritonavir, and verapamil).
- •Have a BMI of 33 or higher.
研究组 & 干预措施
Treatment
干预措施: Daridorexant 50 mg (Drug)
No treatment
干预措施: Placebo (Other)
结局指标
主要结局
Sleep Quality
时间窗: 2 days + 3 weeks study: 2 days to assess sleep prior to taking daridorexant followed by 3 weeks of daily daridorexant administration.
Sleep device to assess: latency to sleep, number of awakenings during the night, and sleep stages.
Sleep Quality-sleep diary
时间窗: Assessed 2 days prior to taking daridorexant and daily for 3 weeks during daily daridorexant administration.
Daily sleep diary to assess self-reported sleep
Daytime alertness
时间窗: Assessed 3 times per day (morning, midday, evening), 3 times per week for 3 weeks.
Assess daytime alertness using a 5 min psychomotor vigilance task. Higher score indicates lower alertness.
Insomnia Severity Index
时间窗: Assess at prescreening and on last day of the study (3 weeks and 2 days)
Assesses extent of insomnia. Range is 0-28. Higher score indicates high level of insomnia.
Pittsburgh Sleep Quality Index
时间窗: 2 days before beginning study medication.
Assesses sleep quality (duration, disturbance, latency) over last 1 month. Range is 0-21; higher score indicates worse sleep quality.
PROMIS Sleep-Short Form 8a
时间窗: 2 days before beginning study medication and last day of weeks 1, 2, 3.
Assesses sleep quality over last 7 days. Range is 8-40, higher score indicates worse sleep/low alertness.
Karolinska Sleepiness Scale
时间窗: Given 3X/day on days 3, 5, 7 of weeks 1, 2, 3.
Assesses daytime alertness - single question. Range is 1-10. Higher score indicates lower alertness.
次要结局
- Fagerstrom(Measure at pre-screening and at the end of each week for 3 weeks.)
- Smoking History and Habits(Measure at pre-screening.)
- Minnesota Scale Withdrawal from Nicotine(2 days before beginning study medication, end of day on days 3, 5, 7 of weeks 1, 2, and 3.)
- QSU Brief Smoking Desire(End of day on days 3, 5, 7 of weeks 1, 2, and 3.)
- Number of cigarettes/vape products smoked(Reported daily for entire study (2 days + 3 weeks).)
研究者
Barbara A. Sorg
Dow Neurobiology Chair
Legacy Health System