Lemborexant for Alzheimer's Disease

Recruiting at 2 trial locations

Overseen By Brendan P. Lucey, M.D.

Age: 65+

Sex: Any

Trial Phase: Phase 2

Sponsor: Washington University School of Medicine

Must not be taking: Sedatives, Lemborexant interactors

Disqualifiers: Stroke, Renal impairment, Hepatic impairment, HIV/AIDS, others

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

Approved in 4 Jurisdictions This treatment is already approved in other countries

Compensation: Varies

Number of Visits: 1

Duration: 6 months

201 Participants Needed

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial explores whether lemborexant, a sleep aid, can reduce certain blood proteins linked to Alzheimer's disease. Researchers aim to determine if it can lower amyloid-beta and tau levels, which contribute to the disease's progression. Participants will take lemborexant or a placebo (a harmless pill with no active ingredients) once a night for six months. The trial is suitable for individuals aged 65 or older who have memory concerns but do not have serious medical conditions like untreated sleep apnea or significant liver issues. As a Phase 2 trial, it measures how well lemborexant works in an initial, smaller group, allowing participants to contribute to important Alzheimer's research.

Will I have to stop taking my current medications?

The trial requires that you stop taking sedating medications and any medications that interact with lemborexant if they cannot be discontinued. If you are on such medications, you may need to stop them to participate in the study.

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

Research has shown that lemborexant is generally safe for use. Studies have found it can improve sleep and make nighttime rest more consistent without major side effects. In one study, participants took lemborexant for four weeks and experienced better sleep patterns without significant issues. Another study confirmed its safety for use over a longer period of one month.

These results are encouraging, especially since the FDA has already approved lemborexant for treating insomnia, indicating its safety as a sleep aid. While researchers continue to explore its use for Alzheimer's disease, the current safety data remains reassuring. ^{1 2 3 4 5}

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

Lemborexant is unique because it offers a novel approach to treating Alzheimer's disease by targeting orexin receptors in the brain, which play a role in regulating sleep-wake cycles. Most current treatments for Alzheimer's focus on managing symptoms related to memory and cognition, often using cholinesterase inhibitors or NMDA receptor antagonists. By contrast, lemborexant specifically addresses sleep disturbances, a common issue in Alzheimer's patients, potentially improving their overall quality of life. Researchers are excited about lemborexant because it not only has a different mechanism of action but also promises to address a critical yet often overlooked aspect of Alzheimer's care.

What evidence suggests that lemborexant might be an effective treatment for Alzheimer's?

Research has shown that lemborexant might help with Alzheimer's disease by lowering certain proteins in the blood, such as amyloid-beta and tau, which are linked to the disease's progression. Some studies have also found that lemborexant improves sleep patterns. Better sleep is important because it might help slow down Alzheimer's. Animal studies have found that lemborexant and similar sleep aids can prevent nerve cell damage related to tau. Additionally, a series of cases involving elderly patients with Alzheimer's showed that lemborexant improved nighttime behaviors and sleep problems. This trial will test lemborexant at two different dosages, 10 mg and 20 mg, to evaluate its effectiveness in managing Alzheimer's symptoms. ^{1 2 3 5 6}

Who Is on the Research Team?

Brendan Lucey, MD

Principal Investigator

Washington University School of Medicine

Are You a Good Fit for This Trial?

This trial is for individuals aged 65 or older with early-stage Alzheimer's disease (Global Clinical Dementia Rating of 0) who can consent to study procedures. They must not have sleep disorders, severe liver or kidney issues, untreated sleep apnea, a high risk of stroke, recent substance abuse, or be on certain medications that interact with lemborexant.

Inclusion Criteria

Any race or ethnicity

I am either male or female.

Willing and able to undergo study procedures

Exclusion Criteria

STOP-Bang score ≥ 6

Body mass index >35

History of substance abuse or alcoholism in the preceding 6 months

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants receive lemborexant or placebo once a night for 6 months to assess its effect on Alzheimer's disease biomarkers

6 months

Monthly visits for monitoring and sample collection

Follow-up

Participants are monitored for safety and effectiveness after treatment

4 weeks

1 visit (in-person)

What Are the Treatments Tested in This Trial?

Interventions

• Lemborexant

Trial Overview The trial tests if lemborexant, a sleep aid at doses of either 10 mg or 20 mg, affects the levels of amyloid-beta and tau proteins in cerebrospinal fluid compared to a placebo. These proteins are associated with the development of Alzheimer's disease.

How Is the Trial Designed?

Group I: Lemborexant 20 mg Experimental Treatment 1 Intervention

Lemborexant is a capsule, taken by mouth once a night, approximately 30 minutes prior to bed for 6 months.

Group II: Lemborexant 10 mg Experimental Treatment 1 Intervention

Lemborexant is a capsule, taken by mouth once a night, approximately 30 minutes prior to bed for 6 months.

Group III: Placebo Placebo Group 1 Intervention

Placebo is in capsule form and contains an inactive substance. It is taken by mouth once a night, approximately 30 minutes prior to bed for 6 months.

Lemborexant is already approved in United States, Canada, Japan for the following indications:

Approved in United States as Dayvigo for:

• Insomnia characterized by difficulties with sleep onset and/or sleep maintenance in adults

Approved in Canada as Dayvigo for:

• Insomnia characterized by difficulties with sleep onset and/or sleep maintenance, with or without associated impairment in daily functioning

Approved in Japan as Dayvigo for:

• Treatment of insomnia

Who Is Running the Clinical Trial?

Washington University School of Medicine

Lead Sponsor

Trials

2,027

Recruited

2,353,000+

National Institute on Aging (NIA)

Collaborator

Trials

1,841

Recruited

28,150,000+

National Institutes of Health (NIH)

Collaborator

Trials

2,896

Recruited

8,053,000+

Eisai Inc.

Industry Sponsor

Trials

524

Recruited

161,000+

Founded

Eisai Inc. was established in 1995 as the U.S. subsidiary of Eisai Co., Ltd.

Headquarters

Woodcliff Lake, NJ, USA

Known For

Neurology and Oncology

Top Products

Aricept (donepezil), Lenvima (lenvatinib), Leqembi (lecanemab), Halaven (eribulin)

Lynn Kramer

Eisai Inc.

Chief Medical Officer since 2019

MD

Tatsuyuki Yasuno

Eisai Inc.

Chief Executive Officer since 2023

MBA from Kellogg School of Management, Northwestern University; Bachelor of Political Science from Waseda University

Citations

1. pubmed.ncbi.nlm.nih.gov pubmed.ncbi.nlm.nih.gov/33336219/

Results From a Phase 2 Randomized Clinical Trial This study provides preliminary evidence of the potential utility of lemborexant as a treatment to address both nighttime and daytime symptoms in patients ...

2. eisai.com eisai.com/news/2018/news201893.html

EISAI PRESENTS NEW DATA ON LEMBOREXANT FOR ... Treatment with lemborexant resulted in an improved 24-hour circadian rhythm pattern with statistically significant reductions in nighttime ...

3. alz-journals.onlinelibrary.wiley.com alz-journals.onlinelibrary.wiley.com/doi/abs/10.1002/alz.039039

Long‐term safety and efficacy of lemborexant in subjects with ... LEM improved circadian variables, helped consolidate nighttime sleep, and was well tolerated, over 1 month.

4. medicine.washu.edu medicine.washu.edu/news/sleep-aid-blocks-neurodegeneration-in-mice/

Sleep aid blocks neurodegeneration in mice Lemborexant, similar sleep drugs, show promise in treating disorders related to tau, such as Alzheimer's disease.

5. sciencedirect.com sciencedirect.com/science/article/pii/S1041610225003606

Adjunctive lemborexant for managing nighttime agitation ... We present a case series of four elderly patients with AD who experienced substantial improvement in nighttime behaviors and sleep disturbances ...

6. clinicaltrials.gov clinicaltrials.gov/study/NCT03001557

NCT03001557 | Study of Lemborexant for Irregular Sleep- ... This study will be conducted to determine the dose response of lemborexant (LEM) on the change from baseline in actigraphy-derived sleep-related parameters.