Study Title: Lemborexant for Alzheimer's Disease Biomarkers
Intervention: Lemborexant (dual orexin receptor antagonist)
Phase: Phase 2
Participants: 201
Status: Recruiting
This trial targets sleep-wake cycle disruption in AD via orexin receptor antagonism:
- Lemborexant: Dual orexin receptor antagonist (OX1R and OX2R)
- Rationale: Orexin/hypocretin system regulates arousal, sleep-wake cycles
- AD connection: Sleep disruption is both a risk factor and symptom of AD; orexin dysregulation contributes to circadian rhythm disturbances
Sleep fragmentation and reduced slow-wave sleep are common in AD and contribute to:
- Impaired memory consolidation
- Increased amyloid clearance disruption (glymphatic function)
- Circadian rhythm disturbances
- Daytime cognitive fluctuations
Orexin receptor antagonism may improve sleep quality and potentially affect AD pathology through improved sleep-dependent clearance mechanisms.
- Change in sleep efficiency at 26 weeks (polysomnography)
- Change in CSF biomarkers (Aβ40, Aβ42, tau, p-tau)
- Change in cognitive measures (ADAS-Cog, MMSE)
- Changes in actigraphy-measured sleep patterns
- Sleep quality correlation with biomarker changes
- Safety and tolerability in AD population
NCT06274528
- ClinicalTrials.gov: NCT06274528