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RecruitingPhase 2

DORA and LP in Alzheimer's Disease Biomarkers

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

Lead sponsor

University of Minnesota

Asset

Lemborexant

Listed sites

Recruiting sites

Enrollment

201

estimated

Study population

Alzheimer’s disease

Key I/E criterion

•Age ≥65

Primary endpoint

•Changes plasma pT181/T181 ratio of lemborexant 10 and 20 mg

Footprint

Where this trial recruits

Site locations as reported to ClinicalTrials.gov. Site count is not enrollment count; per-site enrollment is not available from source.

Identifiers

Registered as

Org study ID202301150

NCT IDNCT06274528

NihR01AG080551

Timeline

Milestones

Study first posted2024-02-23actual

Study start2024-03-11actual

Last update posted2026-07-13actual

Primary completion2030-03-31estimated

Study completion2030-03-31estimated

Assets

Drug assets

Lemborexant

Study populations

Who this study enrolls

Alzheimer’s disease

Eligibility

Who can enroll

Minimum age65 Years

SexAll

Healthy volunteersAccepted

Inclusion criteria

•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

Exclusion criteria

•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

•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).

Endpoints (11)

What's being measured

Protocol endpoints and posted registry outcome measures, grouped into outcome categories. Composite endpoints show their component event types. Standard codes (LOINC, SNOMED CT) are shown where available.

Coverage by outcome category

Fluid / digital biomarkers

Amyloid biomarkers

Tau biomarkers

Neurodegeneration biomarkers

Safety / tolerability / PK

Other (unclassified)

Amyloid biomarkers

2 endpoints

Secondary/protocol endpoint

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

Time frame:6 months

descriptive

Secondary/protocol endpoint

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

Time frame:6 months

descriptive

Tau biomarkers

2 endpoints

Secondary/protocol endpoint

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

Time frame:6 months

descriptive

Secondary/protocol endpoint

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

Time frame:6 months

descriptive

Neurodegeneration biomarkers

2 endpoints

Other/protocol endpoint

Measure changes of cerebrospinal NfL (exploratory)

Time frame:6 months

Neurofilament light (NfL)

descriptive

Other/protocol endpoint

Measure changes of blood plasma NfL (exploratory)

Time frame:6 months

Neurofilament light (NfL)

descriptive

Fluid / digital biomarkers

3 endpoints

Secondary/protocol endpoint

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

Time frame:6 months

concentration, descriptive

Other/protocol endpoint

Measure changes of cerebrospinal TREM2 (exploratory)

Time frame:6 months

descriptive

Other/protocol endpoint

Measure changes of cerebrospinal NPTX2 (exploratory)

Time frame:6 months

descriptive

Safety / tolerability / PK

1 endpoint

Secondary/protocol endpoint

Number of participants with treatment-related adverse events

Time frame:6 months

event count, event

Other (unclassified)

1 endpoint

Primary/protocol endpoint/low confidence

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

Time frame:6 months

ratio, descriptive

Provenance

Sources

Trial identity, design, statusClinicalTrials.gov API v2

Snapshot dateJuly 21, 2026

Endpoint classificationDelfa ADRD endpoint taxonomy

Results tableno registry results posted yet

Trial facts come from public ClinicalTrials.gov records. Endpoint categories are Delfa's classification of those records, not a ClinicalTrials.gov field. All figures reflect the July 21, 2026 snapshot.