A Phase 2 interventional study of Daridorexant 50 mg and Placebo in Alzheimer Disease (AD), sponsored by Douglas Mental Health University Institute. Recruiting at 1 site in Canada. Open to participants aged 50 Years to 90 Years, including healthy volunteers. Per ClinicalTrials.gov, last updated 2025-12-19.
Sponsored by Douglas Mental Health University Institute · Phase 2, Interventional, and Prevention
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.
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.
3,965 studies on the registry are indexed under Alzheimer Disease; 926 are open to participants now.
This study's planned enrollment of 240 is above the median of 70 across 3,019 interventional studies indexed under Alzheimer Disease.
Browse Alzheimer Disease studies →Douglas Mental Health University Institute is the lead sponsor of 39 studies on the registry; 11 are open to participants now.
Counted across the registry records on this site, refreshed daily.
Go through the criteria one by one — yes, no or not sure — and take the list to your doctor or the study team. Kept in this browser only.
Exclusion Criteria:
Underlined terms in the criteria open these too. Explained by clinicaltrials.gg, not part of the registry record. The study team decides who can take part.
Short tests of memory and thinking, each scored out of 30. Lower scores suggest more difficulty; criteria give a range, either to include people with memory problems or to leave them out.
Judged by the study doctor to matter for your health or for the study. It is a doctor’s decision, so ask the study team if you are unsure whether something counts.
CYP3A is a group of enzymes, mainly CYP3A4, in the liver and gut that break down many medicines. Some medicines, supplements and foods (grapefruit, St John’s wort) slow them down or speed them up, which changes how much of a study drug stays in the body.
Studies list them so they can be avoided or switched; bring a list of everything you take, including supplements.
MMSE and MoCA
Short tests of memory and thinking, each scored out of 30. Lower scores suggest more difficulty; criteria give a range, either to include people with memory problems or to leave them out.
Explained by clinicaltrials.gg, not part of the registry record. The study team decides who can take part.
Clinically significant
Judged by the study doctor to matter for your health or for the study. It is a doctor’s decision, so ask the study team if you are unsure whether something counts.
Explained by clinicaltrials.gg, not part of the registry record. The study team decides who can take part.
CYP3A (CYP3A4) inhibitors and inducers
CYP3A is a group of enzymes, mainly CYP3A4, in the liver and gut that break down many medicines. Some medicines, supplements and foods (grapefruit, St John’s wort) slow them down or speed them up, which changes how much of a study drug stays in the body.
Studies list them so they can be avoided or switched; bring a list of everything you take, including supplements.
Explained by clinicaltrials.gg, not part of the registry record. The study team decides who can take part.
Drug: Daridorexant 50 mg
Drug: Placebo
Study drug (Daridorexant 50 mg) taken orally each night 30 minutes before bedtime, for the 1 year duration of the study
Study drug (Placebo) will be taken orally each night, 30 minutes before bedtime, for the 1 year duration of the study
Change in plasma p-tau217/np-tau217 ratio
Biological progression as measured by p-tau217/np-tau217 ratio in plasma
Time frame: baseline up to estimated 12 months
Change in plasma p-tau181/np-tau181 ratio
Biological progression as measured by p-tau181/np-tau181 ratio in plasma
Time frame: baseline up to estimated 12 months
Change in plasma Aβ42/Aβ40 ratio
Biological progression as measured by Aβ42/Aβ40 ratio in plasma
Time frame: baseline up to estimated 12 months
Change from baseline on Preclinical Alzheimer Cognitive Composite (PACC) score
Cognitive progression as measured with a modified version of the Preclinical Alzheimer Cognitive Composite (PACC) score. The PACC score is created by averaging the z-scores of several neuropsychological tests to track subtle changes, where a higher PACC z-score indicates better cognition.
Time frame: baseline up to estimated 12 months
Change from baseline on XpressO MoCA
Cognitive progression as measured with the self-administered digital XpressO MoCA medical screening tool. The maximum possible score is 100 points, with higher values suggesting better cognition.
Time frame: baseline up to estimated 12 months
Change in CSF Aβ42/Aβ42
Change in Aβ42/Aβ40 ratio in cerebrospinal fluid in a subset of participants
Time frame: baseline up to estimated 12 months
Change in sleep efficiency
Change in sleep efficiency as measured by EEG recordings
Time frame: baseline up to estimated 12 months
Change in plasma GFAP
Change in astroglial activation and astrocytosis as measured by glial fibrillary acidic protein (GFAP) levels in plasma.
Time frame: baseline up to estimated 12 months
Change in p-tau181/np-tau181 after 3-months
Biological progression as measured by p-tau181/np-tau181 ratio at 3 months, in plasma.
Time frame: baseline to estimated 3 months
Change in p-tau217/np-tau217 after 3 months
Biological progression as measured by p-tau217/np-tau217 ratio at 3 months, in plasma
Time frame: baseline up to estimated 3 months
Plan to share: Yes — Coded individual participant data will be shared through the StoP-Alzheimer Centre open science initiatives (Repository: registeredpreventad.loris.ca and via the Canadian Open Neuroscience Platform)
Data sharing details ↗ · registeredpreventad.loris.ca
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Studies of the drug tested here: Daridorexant
Douglas Mental Health University Institute