Alzheimer Disease (AD)Phase 2PAD-DORANCT07213349
Daridorexant for Alzheimer Disease Prevention
A Phase 2 study testing Daridorexant 50 mg in people with Alzheimer Disease (AD), run by Douglas Mental Health University Institute at 1 site in Canada.
Trial 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. Read more about this study
- Who is it for?
- Ages 50 to 90 yearsHealthy volunteers can take part
- Conditions the study is for
- Alzheimer Disease (AD)
- What is being tested?
- Daridorexant 50 mg
- Type of treatment
- Pill or oral medicine
- Could I receive a placebo?
- Yes, some participants may receive a placebo
- How many people
- 240 participants
- Where
- 1 siteCanada
- Study dates
- 14 Oct 2025to Dec 2029
- Phase
- Phase 2
- Are there results?
- Not yet: the study is under way
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 50 to 90 years
- All sexes
- Healthy volunteers accepted
- Adult, Older adult
Who may be able to join
- 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
Who cannot join
- 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
Show all 15Show fewer
- 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
Trial locations and contacts
1 site in 1 country. Contact the study team or a site near you to ask about taking part.
Nolan-Patrick Cunningham, BA contact
Canada1 site, 1 recruiting
- Recruiting
Centre StoP-Alzheimer (Douglas Mental Health University Institute - Research Centre)
Montreal, Quebec, H4H 1R3
Sylvia Villeneuve, PhD
Simon Ducharme, MD, PhD
About this study
Official title: Double Blind Clinical Trial of Daridorexant (Dual Orexin Receptor Antagonist) for Alzheimer Disease 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.
Read the 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)
- Being tested
- Daridorexant 50 mg, Placebo
- Keywords
- Prevention, Sleep, Amyloid, Tau, Cognitive decline, Dual Orexin Receptor Antagonist (DORA), Daridorexant
- Medical subject headings
- Alzheimer Disease, Pick Disease of the Brain, Cognitive Dysfunction
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Daridorexant 50 mgDrug
Study drug (Daridorexant 50 mg) taken orally each night 30 minutes before bedtime, for the 1 year duration of the study
PlaceboDrug
Study drug (Placebo) will be taken orally each night, 30 minutes before bedtime, for the 1 year duration of the study
| Study group | Role | What they receive |
|---|---|---|
| Daridorexant 50 mg | Experimental | Not described Receives: Drug: Daridorexant 50 mg |
| Placebo | Placebo comparator | Not described Receives: Drug: Placebo |
What is being measured
The primary outcome is the main question the study is designed to answer.
Change in plasma p-tau217/np-tau217 ratio
Biological progression as measured by p-tau217/np-tau217 ratio in plasma
Measured: baseline up to estimated 12 months
Secondary outcomes (4)
Change in plasma p-tau181/np-tau181 ratio
Biological progression as measured by p-tau181/np-tau181 ratio in plasma
Measured: baseline up to estimated 12 months
Change in plasma Aβ42/Aβ40 ratio
Biological progression as measured by Aβ42/Aβ40 ratio in plasma
Measured: 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.
Measured: 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.
Measured: baseline up to estimated 12 months
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted8 Oct 2025
- Study start14 Oct 2025
- Primary completionDec 2028 (estimated)
- Study completionDec 2029 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Alzheimer Disease (AD)Studies of the same condition, open and under way.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 2
- Primary purpose
- Prevention
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Model description
- This is a single site, double blinded, randomized, placebo-controlled trial
- Masking
- Quadruple blind
- Who is masked
- Participant, Care provider, Investigator, Outcomes assessor
- Enrolment
- 240 participants (estimated)
Sponsor and investigators
- Lead sponsor
- Douglas Mental Health University Institute
- Sponsor type
- University, hospital or other
- Collaborators
- Weston Family Foundation
- Responsible party
- Principal investigator, Sylvia Villeneuve, Douglas Mental Health University Institute
- Investigators
- Sylvia Villeneuve, PhD, Principal investigator, McGill University
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT07213349
- Sponsor's protocol ID
- DARAD2025
- Other IDs
- BH-10983
- Acronym
- PAD-DORA
- Status last verified
- Dec 2025
- First submitted
- 24 Sep 2025
- Last updated
- 19 Dec 2025
- Results posted
- No
- Data monitoring committee
- Yes
- FDA-regulated drug
- No
- FDA-regulated device
- No
- Individual data sharing
- 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)
Study at a glance
From the registry record, last updated by the sponsor on 19 Dec 2025. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Double Blind Clinical Trial of Daridorexant (Dual Orexin Receptor Antagonist) for Alzheimer Disease Prevention
- ClinicalTrials.gov ID
- NCT07213349
- Acronym / sponsor ID
- PAD-DORA / DARAD2025
- Conditions
- Alzheimer Disease (AD)
- Keywords
- Prevention, Sleep, Amyloid, Tau, Cognitive decline, Dual Orexin Receptor Antagonist (DORA), Daridorexant
- Phase
- Phase 2
- Study type
- Interventional
- Recruitment status
- Recruiting
- Enrolment
- 240 participants (estimated)
- Lead sponsor
- Douglas Mental Health University InstituteUniversity, hospital or other
- Collaborators
- Weston Family Foundation
- Study start
- 14 Oct 2025 (actual)
- Primary completion
- Dec 2028 (estimated)
- Study completion
- Dec 2029 (estimated)
- First posted
- 8 Oct 2025 (actual)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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.
Study design
- Primary purpose
- Prevention
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Quadruple blind (participant, care provider, investigator, outcomes assessor)
- Number of arms
- 2
- Model description
- This is a single site, double blinded, randomized, placebo-controlled trial
| Arm | Type | Receives |
|---|---|---|
| Daridorexant 50 mg | Experimental | Drug: Daridorexant 50 mg |
| Placebo | Placebo comparator | Drug: Placebo |
Who may qualify
- Ages
- 50 to 90 years
- Sex
- All
- Healthy volunteers
- Accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (4 listed)
- 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
Key exclusion criteria (15 listed)
- 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
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| Daridorexant 50 mgStudy drug (Daridorexant 50 mg) taken orally each night 30 minutes before bedtime, for the 1 year duration of the study | Drug | Daridorexant 50 mg |
| PlaceboStudy drug (Placebo) will be taken orally each night, 30 minutes before bedtime, for the 1 year duration of the study | Drug | Placebo |
Primary outcome
Change in plasma p-tau217/np-tau217 ratio
Time frame: baseline up to estimated 12 months
Biological progression as measured by p-tau217/np-tau217 ratio in plasma
4 secondary outcomes
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
Results and safety
This study is still under way. Results are not available in the source record yet.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 19 Dec 2025.
- Individual participant dataSharing planned: 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)
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part.
Nolan-Patrick Cunningham, BA contact
Sylvia Villeneuve, PhD principal investigator
McGill University
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 2 study testing Daridorexant 50 mg in people with Alzheimer Disease (AD), run by Douglas Mental Health University Institute at 1 site in Canada.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 4 inclusion and 15 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: looking for participants now, as of the sponsor's last update on 19 Dec 2025. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in Canada. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. Some participants in this study may receive a placebo. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
This study is still under way. Results are not available in the source record yet.
How can a doctor refer a patient or contact the research team?
Contact Jennifer Tremblay-Mercier, MSc (855-888-4485, prevenir.alzheimer@douglas.mcgill.ca), or a site near the patient. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Change in plasma p-tau217/np-tau217 ratio (time frame: baseline up to estimated 12 months). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 19 Dec 2025.