NCT07328594

Impact of Daridorexant on Sleep, Daytime Alertness, and Smoking

Impact of Daridorexant on Sleep, Daytime Alertness, and Smoking During Abstinence

• Status: Not Yet Recruiting
• Phase: Phase 4
• Study type: Interventional
• Enrollment: 44 (estimated)
• Sponsor: Legacy Health System · Academic / Other
• Sex: All
• Age: 18 Years – 55 Years
• Healthy volunteers: Not accepted

Summary

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.

Detailed description

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.

Conditions

• Smoking
• Nicotine
• Tobacco
• Addiction
• Substance Use Disorders
• Insomnia
• Sleep

Interventions

Type	Name	Description
DRUG	Daridorexant 50 mg	Active daridorexant vs placebo comparator in smokers with insomnia
OTHER	Placebo	Placebo in Smokers

Timeline

• Start date: 2026-02-10
• Primary completion: 2027-03-31
• Completion: 2027-09-30
• First posted: 2026-01-09
• Last updated: 2026-01-09

Locations

1 site across 1 country: United States

Regulatory

• FDA-regulated drug study