Daridorexant for Alzheimer's Disease Prevention

(PAD-DORA Trial)

Overseen By Nolan-Patrick Cunningham, BA

Age: 18+

Sex: Any

Trial Phase: Phase 2

Sponsor: Douglas Mental Health University Institute

Must not be taking: DORA, Benzodiazepines, Antipsychotics, others

Disqualifiers: Major neurocognitive disorder, Unstable psychiatric condition, Drug or alcohol dependence, Severe OSA, others

Prior Safety Data This treatment has passed at least one previous human trial

Compensation: Varies

Number of Visits: Unknown

Duration: 12 months

240 Participants Needed

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial tests whether daridorexant, a medication typically used for sleep, can help maintain brain health. Researchers aim to determine if it can clear proteins that may lead to Alzheimer's disease. The study includes individuals without Alzheimer's, regardless of sleep issues. It may suit those without major memory problems who are not using certain sleep or psychiatric medications. Participants will receive either the actual medication or a placebo (a pill with no active ingredients). As a Phase 2 trial, this research focuses on assessing the treatment's effectiveness in an initial, smaller group of people.

Do I have to stop taking my current medications for the trial?

You may need to stop taking certain medications to join the trial. Specifically, you cannot use benzodiazepines, z-drugs, certain antidepressants, antipsychotics, or medications that affect the central nervous system. It's best to discuss your current medications with the trial team to see if any changes are needed.

Is there any evidence suggesting that daridorexant is likely to be safe for humans?

Research has shown that daridorexant is usually well-tolerated. Previous studies highlight its safety, making it a promising option for preventive treatments. However, the safety of daridorexant for use longer than one year remains underexplored, indicating potential unknown risks with long-term use. Prospective trial participants can use this information to discuss any concerns with the research team. ^{1 2 3 4 5}

Why do researchers think this study treatment might be promising for Alzheimer's?

Researchers are excited about daridorexant for Alzheimer's disease prevention because it offers a novel approach compared to current treatments. Unlike existing medications that generally focus on managing symptoms or slowing progression by targeting neurotransmitter imbalances, daridorexant works as an orexin receptor antagonist. This unique mechanism aims to regulate sleep-wake cycles, which are often disrupted in Alzheimer's patients and may play a role in disease progression. By potentially improving sleep and its associated health benefits, daridorexant could offer a new avenue for preventing or delaying the onset of Alzheimer's, setting it apart from standard treatments like donepezil or memantine.

What evidence suggests that daridorexant might be an effective treatment for Alzheimer's disease prevention?

Studies have shown that daridorexant, a sleep medication, can improve sleep quality. Better sleep may help clear proteins linked to Alzheimer's disease. Although no direct evidence shows that daridorexant prevents Alzheimer's, research suggests it might support brain health by improving sleep, potentially lowering the risk of developing Alzheimer's. In this trial, participants will receive either daridorexant or a placebo to investigate these potential effects further. Ongoing research aims to confirm these effects. ^{1 2 3 4 6}

Who Is on the Research Team?

Sylvia Villeneuve, PhD

Principal Investigator

McGill University

Are You a Good Fit for This Trial?

This trial is for people without dementia (confirmed by cognitive tests) who have at least 6 years of education and can consent in English or French. They must not plan to change their stable psychoactive meds during the study. Excluded are those with recent substance abuse, allergies to DORA, unstable health conditions, use of certain drugs affecting brain function or metabolism, pregnant/breastfeeding women, severe sleep apnea sufferers, and users of similar sleep aids more than twice a week recently.

Inclusion Criteria

Without dementia as determined by MoCA >21 or MMSE > 24 or Clinical Dementia Rating <1

Minimum of 6 years of formal education

Capacity to provide written consent in English or French

Exclusion Criteria

Unstable psychiatric condition with clinically significant active suicidal ideations

Known or suspected history of drug or alcohol dependence or abuse within one year of the screening visit

Allergy or significant adverse reaction to DORA

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants receive 50 mg of daridorexant or placebo over 12 months

12 months

Follow-up

Participants are monitored for safety and effectiveness after treatment

4 weeks

What Are the Treatments Tested in This Trial?

Interventions

• Daridorexant

Trial Overview

The trial is testing Daridorexant 50 mg against a placebo to see if it helps prevent Alzheimer's by improving brain protein clearance during sleep. It's designed for individuals without Alzheimer's dementia and includes participants regardless of existing sleep issues.

How Is the Trial Designed?

Group I: Daridorexant 50 mg Experimental Treatment 1 Intervention

Group II: Placebo Placebo Group 1 Intervention

Who Is Running the Clinical Trial?

Douglas Mental Health University Institute

Lead Sponsor

Trials

31

Recruited

2,800+

Weston Family Foundation

Collaborator

Citations

1.

clinicaltrials.gov

clinicaltrials.gov/study/NCT07213349

Daridorexant for Alzheimer Disease Prevention

The primary biological outcome is the change from baseline to 12 months in the plasma ratio of phosphorylated tau181 to unphosphorylated tau181 ...

2.

isrctn.com

isrctn.com/ISRCTN63918057

Daridorexant for Alzheimer's disease prevention

This study will evaluate whether daridorexant, a sleep medication (Dual Orexin Receptor Antagonist (DORA)), can support brain health by promoting the clearance ...

3.

alzdiscovery.org

alzdiscovery.org/uploads/cognitive_vitality_media/Daridorexant_%28drug%29.pdf

Daridorexant

Neuroprotective Benefit: Daridorexant improves sleep parameters in people with insomnia, which in turn may benefit brain health. No clinical data on ...

4.

nature.com

nature.com/articles/s44323-025-00025-5

Dual orexin receptor antagonists as promising therapeutics ...

Further, we explore dual orexin receptor antagonists (DORAs) potential to mitigate AD sleep disturbances and enhance clearance. Further research ...

5.

pmc.ncbi.nlm.nih.gov

pmc.ncbi.nlm.nih.gov/articles/PMC11602839/

Orexin Receptor Antagonists for the Prevention and Treatment ...

Overall, clinical studies support the use of DORAs to enhance sleep quality in patients with AD with comorbid sleep and circadian sleep–wake rhythm disorders.

6.

sciencedirect.com

sciencedirect.com/science/article/abs/pii/S1064748124004809

Efficacy And Safety of Dual Orexin Receptor Antagonist ...

Findings suggest that suvorexant may improve total sleep time (TST), wakefulness after sleep onset (WASO), and sleep efficiency (SE) in Alzheimer's patients ...