Daridorexant for Alzheimer Disease Prevention (PAD-DORA)

Douglas Mental Health University Institute

Status and phase

Enrolling

Phase 2

Conditions

Alzheimer Disease (AD)

Treatments

Drug: Placebo

Drug: Daridorexant 50 mg

Study type

Interventional

Funder types

Other

Identifiers

NCT07213349

BH-10983 (Other Grant/Funding Number)

DARAD2025

Details and patient eligibility

About

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.

Full 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.

Enrollment

240 estimated patients

Sex

All

Ages

50 to 90 years old

Volunteers

Accepts Healthy Volunteers

Inclusion criteria

Without dementia as determined by: MoCA >21 or MMSE > 24 or Clinical Dementia Rating <1
Minimum of 6 years of formal education
Stable psychoactive medication for 1 month prior to screening with no intention to change dose during treatment period
Capacity to provide written consent in English or French

Exclusion criteria

Clinical diagnosis of major neurocognitive disorder
Unstable psychiatric condition:
Clinically significant active suicidal ideations
Unstable medical condition in the opinion of the investigator.
Known or suspected history of drug or alcohol dependence or abuse within one year of the screening visit
Currently taking a DORA
Allergy or significant adverse reaction to DORA
Use of benzodiazepines or z-drugs > 2 times per week in the last month.
Use of major and moderate CYP3A4 inducers and inhibitors
Use of strong central nervous system depressants, opioids, strong analgesics, antipsychotics, sedative antidepressants.
Active use of cholinesterase inhibitors or memantine
Women who are breast feeding or pregnant
Severe obstructive sleep apnea (OSA)*
Clinically significant non-treated rapid eye movement (REM) sleep behavior disorder, restless leg syndrome or parasomnia;
Diagnosis of narcolepsy