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Alzheimer DiseasePhase 2NCT06274528

DORA and LP in Alzheimer's Disease Biomarkers

A Phase 2 study testing Lemborexant 10 mg and Lemborexant 20mg in people with Alzheimer Disease, run by University of Minnesota at 1 site in United States.

Recruiting

Looking for participants now. Contact the study team or a site below to ask about taking part.

Sites and contacts
Official record
Search all trials

Trial summary

The purpose of this study is to see if the sleep aid, lemborexant, can decrease the amount of amyloid-beta and tau in the blood. Amyloid-beta and tau are proteins involved in the disease process leading to Alzheimer's disease. Read more about this study

Who is it for?
Ages 65 years and olderHealthy volunteers can take part
Conditions the study is for
Alzheimer Disease
What is being tested?
Lemborexant 10 mg and Lemborexant 20mg
Type of treatment
Pill or oral medicine
Could I receive a placebo?
Yes, some participants may receive a placebo
How many people
201 participants
Where
1 siteUnited States
Study dates
11 Mar 2024to 31 Mar 2030
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 65 years and older
  • All sexes
  • Healthy volunteers accepted
  • Older adult

Who may be able to join

  • Male or female.
  • Any race or ethnicity.
  • Participants must be age ≥ 65 years and able to sign informed consent.
  • Global Clinical Dementia Rating (CDR) 0.
  • Willing and able to undergo study procedures.

Who cannot join

  • History or reported symptoms suggestive of restless legs syndrome, narcolepsy, or parasomnia.
  • STOP-Bang score >6 for participants without PAP.
  • Untreated sleep apnea AHI>15
  • Poorly treated sleep apnea due to noncompliance or an AHI ≥ 10.
  • PAP compliance is defined as ≥ 4 hours per night >70% of the nights.
  • Plasma p-Tau217/np-Tau217% <2.5
Show all 35Show fewer
  • Stroke.
  • History of renal impairment
  • Defined as older adult patients with markers of kidney damage or eGFR < 45.0 ml/min/1.73m2.
  • Normal Limits ≥ 45.0 mL/min/1.73m2
  • History of hepatic impairment
  • AST and/or ALT ≥ 2X upper limit of normal (ULN).
  • Normal Limits: AST 11-47 IU/L and ALT 6-53 IU/L
  • HIV/AIDS.
  • History of substance abuse or alcohol abuse in the preceding 6 months.
  • Regular alcohol consumption 3 or more days a week over the last 6 months. Regular alcohol consumption is defined as having more than 2 alcoholic beverages within 3 hours of bedtime. Participants that agree to reduce alcohol consumption during the study may not be excluded.
  • History of presence of any clinically significant medical condition, behavioral or psychiatric disorder, or surgical history based on medical record or participant report that could affect the safety of the participant or interfere with study assessments or in the judgement of the Principal-Investigator (PI) if participant is not a good candidate.
  • Has any medical condition that, in the PI's or study team investigator's opinion, could increase risk to the participant, limit the participant's ability to tolerate the research procedures, or interfere with the collection/analysis of the data. Potential medical conditions that will be exclusionary at the PI's or study team investigator's discretion:
  • Cardiovascular disease requiring medication except for controlled hypertension.
  • Pulmonary disease.
  • Type I diabetes.
  • Neurologic or psychiatric disorder requiring medication.
  • Untreated depression
  • Tobacco use.
  • Use of sedating medications.
  • Use of medications that interact with lemborexant (if cannot be discontinued).
  • Abnormal safety labs.
  • History of current suicidal ideations.
  • Inability to speak and understand English.
  • Currently pregnant or breast-feeding.
  • In the opinion of the PI, the participant should be excluded due to an abnormal physical examination.
  • Must not have participated in any clinical trial involving a study drug or device within the 30-days prior to study enrollment.
  • Must not participate in another drug or device study prior to the end of this study participation.
  • Optional assessment exclusion criteria:
  • Contraindication to lumbar puncture (anticoagulants; bleeding disorder; allergy to lidocaine or disinfectant; prior central nervous system or lower back surgery).

Trial locations and contacts

1 site in 1 country. Contact the study team or a site near you to ask about taking part.

Chloe Meehan, MA contact

314-273-0878

cmeehan@wustl.edu

Crirstina Toedebusch contact

314-747-0646

toedebuschc@wustl.edu

United States1 site, 1 recruiting

  • Washington University in St. Louis, School of Medicine

    St Louis, Missouri, 63110

    Cristina Toedebusch, BS, 314-747-0646, toedebuschc@wustl.edu

    Chloe Meehan, BS, MA, 314-273-0878, cmeehan@wustl.edu

    Recruiting

Other trials in United States

About this study

Official title: Effect of a Dual Orexin Receptor Antagonist on CSF Alzheimer's Disease Biomarkers

The purpose of this study is to see if the sleep aid, lemborexant, can decrease the amount of amyloid-beta and tau in the blood. Amyloid-beta and tau are proteins involved in the disease process leading to Alzheimer's disease.

Read the detailed description

The overall goal of this project is to conduct an early stage (phase II) clinical trial of a dual orexin receptor antagonist (DORA), lemborexant, in cognitively normal older adults with amyloid deposition to demonstrate the feasibility and potential biological effectiveness of lemborexant's target engagement with multiple blood plasma and cerebrospinal fluid (CSF) Alzheimer's disease (AD) biomarkers. Orexins (also called hypocretins) are wake-promoting neuropeptides and blockade of orexin with a DORA increases sleep. The scientific premise of this project is that increased or enhanced sleep over 6 months by treatment with lemborexant will decrease the ratio of phosphorylated tau-181/tau-181 (pT181/T181) in blood and the concentration of CSF and plasma AD biomarkers (amyloid-β (Aβ), tau and phosphorylated tau (p-tau)) as well as neurodegeneration, inflammatory and synaptic AD biomarkers such as neurofilament light chain (NfL) (a non-tau marker of neuronal degeneration), soluble triggering receptor expressed on myeloid cells 2 (sTREM2) (a marker for immune response/microglial function), and neuronal pentraxin-2 (NPTX2) a marker for synaptic function) compared to placebo in amyloid-positive cognitively normal older adults. In addition, the investigators will also determine lemborexant's safety, pharmacokinetics (PK), and pharmacodynamics (PD) in this population. This study will enhance trial design and methods by providing critical information about dosing, safety, and target engagement of lemborexant on CSF and blood AD biomarkers to power phase III secondary prevention trials using lemborexant.

Being tested
Lemborexant 10 mg, Lemborexant 20mg, Placebo
Keywords
Sleep, Older Adults, DORA
Medical subject headings
Alzheimer Disease

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

  • Lemborexant 10 mgDrug

    Also called DAYVIGO

    Within FDA approved dose 10 mg; capsule; QD, 6 month duration

  • Lemborexant 20mgDrug

    Also called DAYVIGO

    20 mg; capsule; QD; 6 month duration

  • PlaceboDrug

    0 mg; capsule; QD; 6 month duration

Study groups in NCT06274528
Study groupRoleWhat they receive
Lemborexant 10 mgExperimentalLemborexant is a capsule, taken by mouth once a night, approximately 30 minutes prior to bed for 6 months.
Receives: Drug: Lemborexant 10 mg
Lemborexant 20 mgExperimentalLemborexant is a capsule, taken by mouth once a night, approximately 30 minutes prior to bed for 6 months.
Receives: Drug: Lemborexant 20mg
PlaceboPlacebo comparatorPlacebo 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.
Receives: Drug: Placebo

What is being measured

The primary outcome is the main question the study is designed to answer.

  1. Changes plasma pT181/T181 ratio of lemborexant 10 and 20 mg compared to Placebo

    plasma collection

    Measured: 6 months

Secondary outcomes (6)

  1. Number of participants with treatment-related adverse events

    Adverse events

    Measured: 6 months

  2. Measure the blood concentration of lemborexant 10 mg and 20 mg and determine the dose-response relationship with CSF pT181/T181

    Blood collection

    Measured: 6 months

  3. Measure changes on blood plasma amyloid-beta isoforms (Aβ38, Aβ40, Aβ42, Aβ42/Aβ40)

    Blood collection

    Measured: 6 months

  4. Measure changes of CSF amyloid beta isoforms (Aβ38, Aβ40, Aβ42,Aβ42/Aβ40 )

    CSF collection

    Measured: 6 months

  5. Measure changes of blood plasma p-tau/tau forms (T181, pT181, pT181/T181, S202, pS202, pS202/S202, T217, pT217, pT217/T217).

    Blood collection

    Measured: 6 months

  6. Measure changes of cerebrospinal fluid p-tau/tau forms (T181, pT181, S202, pS202, pS202/S202, T217, pT217, pT217/T217).

    CSF collection

    Measured: 6 months

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

  1. First posted23 Feb 2024
  2. Study start11 Mar 2024
  3. Primary completion31 Mar 2030 (estimated)
  4. Study completion31 Mar 2030 (estimated)

Resources

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
Treatment
Allocation
Randomised
Intervention model
Parallel groups
Masking
Triple blind
Who is masked
Participant, Care provider, Investigator
Enrolment
201 participants (estimated)
IDs, dates and publications
ClinicalTrials.gov ID
NCT06274528
Sponsor's protocol ID
202301150
Other IDs
R01AG080551
Status last verified
Jul 2026
First submitted
29 Jan 2024
Last updated
13 Jul 2026
Results posted
No
Data monitoring committee
Yes
FDA-regulated drug
Yes
FDA-regulated device
No

Questions about this trial

What is this clinical trial studying?

A Phase 2 study testing Lemborexant 10 mg and Lemborexant 20mg in people with Alzheimer Disease, run by University of Minnesota at 1 site in United States.

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 5 inclusion and 35 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 13 Jul 2026. 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 United States. 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 Chloe Meehan, MA (314-273-0878, cmeehan@wustl.edu), or a site near the patient. AzTrials does not enrol participants or take referrals.

What does the primary outcome measure?

Changes plasma pT181/T181 ratio of lemborexant 10 and 20 mg compared to Placebo (time frame: 6 months). It is what the study was designed to measure, not a finding.

Where can I read the original study information?

On the ClinicalTrials.gov record for NCT06274528.

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 13 Jul 2026.

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DORA and LP in Alzheimer's Disease Biomarkers | AzTrials