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.
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.
Study Type
INTERVENTIONAL
Allocation
RANDOMIZED
Purpose
TREATMENT
Masking
QUADRUPLE
Enrollment
44
Active daridorexant vs placebo comparator in smokers with insomnia
Placebo in Smokers
Legacy Research Institute
Portland, Oregon, United States
Sleep Quality
Sleep device to assess: latency to sleep, number of awakenings during the night, and sleep stages.
Time frame: 2 days + 3 weeks study: 2 days to assess sleep prior to taking daridorexant followed by 3 weeks of daily daridorexant administration.
Daytime alertness
Assess daytime alertness using a 5 min psychomotor vigilance task. Higher score indicates lower alertness.
Time frame: Assessed 3 times per day (morning, midday, evening), 3 times per week for 3 weeks.
Insomnia Severity Index
Assesses extent of insomnia. Range is 0-28. Higher score indicates high level of insomnia.
Time frame: Assess at prescreening and on last day of the study (3 weeks and 2 days)
Sleep Quality-sleep diary
Daily sleep diary to assess self-reported sleep
Time frame: Assessed 2 days prior to taking daridorexant and daily for 3 weeks during daily daridorexant administration.
Pittsburgh Sleep Quality Index
Assesses sleep quality (duration, disturbance, latency) over last 1 month. Range is 0-21; higher score indicates worse sleep quality.
Time frame: 2 days before beginning study medication.
PROMIS Sleep-Short Form 8a
Assesses sleep quality over last 7 days. Range is 8-40, higher score indicates worse sleep/low alertness.
Time frame: 2 days before beginning study medication and last day of weeks 1, 2, 3.
Karolinska Sleepiness Scale
Assesses daytime alertness - single question. Range is 1-10. Higher score indicates lower alertness.
Time frame: Given 3X/day on days 3, 5, 7 of weeks 1, 2, 3.
Fagerstrom
Assesses extent of nicotine dependence. Range is 0-10. Higher score indicates higher dependence.
Time frame: Measure at pre-screening and at the end of each week for 3 weeks.
Smoking History and Habits
Must smoke 10 or more cigarettes per day.
Time frame: Measure at pre-screening.
Minnesota Scale Withdrawal from Nicotine
Assesses nicotine withdrawal symptoms over last 24 hr. Range is 0-60, higher score indicating higher withdrawal signs/symptoms.
Time frame: 2 days before beginning study medication, end of day on days 3, 5, 7 of weeks 1, 2, and 3.
QSU Brief Smoking Desire
Assesses desire to smoke. Range 7-49. Higher score indicates higher craving to smoke.
Time frame: End of day on days 3, 5, 7 of weeks 1, 2, and 3.
Number of cigarettes/vape products smoked
Daily Sleep Diary includes number of cigarettes/vape products smoked.
Time frame: Reported daily for entire study (2 days + 3 weeks).
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