NCT07213349

Daridorexant for Alzheimer Disease Prevention

Double Blind Clinical Trial of Daridorexant (Dual Orexin Receptor Antagonist) for Alzheimer Disease Prevention

• Status: Recruiting
• Phase: Phase 2
• Study type: Interventional
• Enrollment: 240 (estimated)
• Sponsor: Douglas Mental Health University Institute · Academic / Other
• Sex: All
• Age: 50 Years – 90 Years
• Healthy volunteers: Accepted

Summary

This study will evaluate whether daridorexant, a DORA sleep medication, can support brain health by promoting the clearance of proteins linked to the development and progression of Alzheimer's disease. The trial is preventive and is open to participants who do not have Alzheimer's disease dementia, regardless of whether or not they experience sleep problems.

Detailed description

Alzheimer's disease (AD) begins decades before symptoms with the accumulation of amyloid plaques and tau tangles, and interventions that slow or prevent this process could greatly reduce its impact. Dual orexin receptor antagonists (DORAs), drugs developed for insomnia, may help clear amyloid and tau, reduce neuroinflammation, and improve cognition through mechanisms that could be both related and unrelated to sleep quality. Early animal and human studies suggest that DORAs can alter biomarkers of Alzheimer's pathology making the orexin pathway modulation a promising strategy for Alzheimer's prevention. Daridorexant, one of the two DORAs available in Canada, stands out as a well-tolerated candidate for prevention due to its safety profile. We want to evaluate the potential of Daridorexant for prevention of AD in this single-site, double-blind, randomized (1:1), placebo-controlled trial evaluating 50 mg of daridorexant versus placebo over 12 months in 240 participants. The primary biological outcome is the change from baseline to 12 months in the plasma ratio of phosphorylated tau181 to unphosphorylated tau181 (p-tau181/np-tau181). Secondary outcomes include changes in additional plasma biomarkers, cognitive performance, sleep parameters, and safety measures.

Conditions

• Alzheimer Disease (AD)

Interventions

Type	Name	Description
DRUG	Daridorexant 50 mg	Study drug (Daridorexant 50 mg) taken orally each night 30 minutes before bedtime, for the 1 year duration of the study
DRUG	Placebo	Study drug (Placebo) will be taken orally each night, 30 minutes before bedtime, for the 1 year duration of the study

Timeline

• Start date: 2025-10-14
• Primary completion: 2028-12-01
• Completion: 2029-12-01
• First posted: 2025-10-08
• Last updated: 2025-12-19

Locations

1 site across 1 country: Canada