Daridorexant for Alzheimer Disease Prevention

NCT07213349 | Recruiting Phase 2 DMC

• 2 other identifiers: DARAD2025BH-10983
• Study Type: interventional
• Target: 240
• Locations: 1 country
• Sites: 1

Brief 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.

Conditions

Alzheimer Disease (AD)

Keywords

Prevention; Sleep; Amyloid; Tau; Cognitive decline; Dual Orexin Receptor Antagonist (DORA); Daridorexant

Outcome Measures

Primary Outcomes (1)

• Change in plasma p-tau217/np-tau217 ratio

  Biological progression as measured by p-tau217/np-tau217 ratio in plasma

  baseline up to estimated 12 months

Secondary Outcomes (4)

• Change in plasma p-tau181/np-tau181 ratio

  baseline up to estimated 12 months

• Change in plasma Aβ42/Aβ40 ratio

  baseline up to estimated 12 months

• Change from baseline on Preclinical Alzheimer Cognitive Composite (PACC) score

  baseline up to estimated 12 months

• Change from baseline on XpressO MoCA

  baseline up to estimated 12 months

Other Outcomes (5)

• Change in CSF Aβ42/Aβ42

  baseline up to estimated 12 months

• Change in sleep efficiency

  baseline up to estimated 12 months

• Change in plasma GFAP

  baseline up to estimated 12 months

Study Arms (2)

Daridorexant 50 mg

EXPERIMENTAL

Drug: Daridorexant 50 mg

Placebo

PLACEBO COMPARATOR

Drug: Placebo

Interventions

Daridorexant 50 mg DRUG

Study drug (Daridorexant 50 mg) taken orally each night 30 minutes before bedtime, for the 1 year duration of the study

Daridorexant 50 mg

Placebo DRUG

Study drug (Placebo) will be taken orally each night, 30 minutes before bedtime, for the 1 year duration of the study

Placebo

Eligibility Criteria

• Age: 50 Years - 90 Years
• Sex: all
• Healthy Volunteers: Yes
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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

You may not qualify if:

• 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

Sponsors & Collaborators

• Douglas Mental Health University Institute: lead
• Weston Family Foundation: collaborator

Study Sites (1)

Centre StoP-Alzheimer (Douglas Mental Health University Institute - Research Centre)

Montreal, Quebec, H4H 1R3, Canada

RECRUITING

MeSH Terms

Conditions

Alzheimer Disease; Pick Disease of the Brain; Cognitive Dysfunction

Interventions

daridorexant

Condition Hierarchy (Ancestors)

Dementia; Brain Diseases; Central Nervous System Diseases; Nervous System Diseases; Tauopathies; Neurodegenerative Diseases; Neurocognitive Disorders; Mental Disorders; Frontotemporal Dementia; Frontotemporal Lobar Degeneration; Cognition Disorders

Study Officials

• Sylvia Villeneuve, PhD

  McGill University

  PRINCIPAL INVESTIGATOR

Central Study Contacts

Jennifer Tremblay-Mercier, MSc

CONTACT

855-888-4485; prevenir.alzheimer@douglas.mcgill.ca

Nolan-Patrick Cunningham, BA

CONTACT

15147616131; nolan-patrick.cunningham.comtl@ssss.gouv.qc.ca

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: QUADRUPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR, OUTCOMES ASSESSOR
• Masking Details: Research Staff (Research Assistants, Nurse, Coordinators)
• Purpose: PREVENTION
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Director of the StoP-AD Centre

Model Details: This is a single site, double blinded, randomized, placebo-controlled trial

Study Record Dates

• First Submitted: September 24, 2025
• First Posted: October 8, 2025
• Study Start: October 14, 2025
• Primary Completion (Estimated): December 1, 2028
• Study Completion (Estimated): December 1, 2029
• Last Updated: December 19, 2025

Record last verified: 2025-12

Data Sharing

• IPD Sharing: Will share

Locations

CA (1)