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Recruiting NCT07213349

Daridorexant for Alzheimer Disease Prevention

Phase II Interventional Alzheimer Disease (AD)

For patients and families

In plain language

An automatic summary of structured registry data. It is an orientation aid, not a substitute for the official protocol or a physician assessment.

What is being studied
The protocol lists: Daridorexant 50 mg, Placebo.
Who it may be relevant to
Registry conditions: Alzheimer Disease (AD). Basic parameters: 50 years — 90 years · All.
What needs checking
Age, condition and sex are only basic indicators. Prior treatment, laboratory values and other mandatory requirements appear in the eligibility criteria below.
Where it takes place
Canada
Next step
Save the trial, show it to the treating physician, and confirm current recruitment with the study center. Costs, documents and travel →

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Official title

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

Overview

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.

Interventions

  • 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

Primary outcome measures

  • Change in plasma p-tau217/np-tau217 ratio [Time frame: baseline up to estimated 12 months]
Secondary outcome measures (4)
  • Change in plasma p-tau181/np-tau181 ratio [Time frame: baseline up to estimated 12 months]
  • Change in plasma Aβ42/Aβ40 ratio [Time frame: baseline up to estimated 12 months]
  • Change from baseline on Preclinical Alzheimer Cognitive Composite (PACC) score [Time frame: baseline up to estimated 12 months]
  • Change from baseline on XpressO MoCA [Time frame: baseline up to estimated 12 months]

Eligibility criteria

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

Criteria are shown verbatim from the registry (in English). Final eligibility is always assessed by the study center.

Healthy volunteers: Yes

Study design

Allocation
Randomized
Model
Parallel assignment
Masking
Quadruple blind
Primary purpose
Prevention

Study locations

Canada · 1 center
  • Centre StoP-Alzheimer (Douglas Mental Health University Institute - Research Centre) — Montreal

Identifiers

NCT: NCT07213349 · DARAD2025 · BH-10983

Primary sources (government registries)

View this study on ClinicalTrials.gov ↗