NCT06274528

DORA and LP in Alzheimer's Disease Biomarkers

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

• Status: Recruiting
• Phase: Phase 2
• Study type: Interventional
• Enrollment: 201 (estimated)
• Sponsor: Washington University School of Medicine · Academic / Other
• Sex: All
• Age: 65 Years
• Healthy volunteers: Accepted

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.

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.

Conditions

• Alzheimer Disease

Interventions

Type	Name	Description
DRUG	Lemborexant 10 mg	Within FDA approved dose 10 mg; capsule; QD, 6 month duration
DRUG	Lemborexant 20mg	20 mg; capsule; QD; 6 month duration
DRUG	Placebo	0 mg; capsule; QD; 6 month duration

Timeline

• Start date: 2024-03-11
• Primary completion: 2029-03-11
• Completion: 2029-03-11
• First posted: 2024-02-23
• Last updated: 2025-11-05

Locations

1 site across 1 country: United States

Regulatory

• FDA-regulated drug study