NCT07217912 is a Phase 2 clinical trial conducted by the University of Rochester testing Daridorexant, a dual orexin receptor antagonist (DORA), to prevent delirium following heart surgery (post-cardiotomy delirium). This trial leverages the growing evidence that orexin receptor antagonism may have neuroprotective effects beyond just promoting sleep[1][2].
| Attribute | Details |
|---|---|
| NCT Number | NCT07217912 |
| Sponsor | University of Rochester |
| Principal Investigator | Mark Oldham, MD (Associate Professor of Psychiatry) |
| Intervention | Daridorexant 50 mg (or 25 mg with moderate CYP3A4 inhibitor) orally for first 3 nights post-surgery |
| Comparator | Matching placebo |
| Phase | Phase 2 |
| Indication | Post-cardiotomy delirium prevention |
| Status | Recruiting |
| Enrollment | 80 participants |
| Start Date | October 14, 2025 |
| Primary Completion | November 1, 2027 (estimated) |
| Location | Strong Memorial Hospital, Rochester, New York |
Postoperative delirium is a common complication following cardiac surgery, affecting up to 50% of elderly patients. It is characterized by:
Post-cardiotomy delirium is associated with:
The orexin system (also known as hypocretin system) consists of orexin-A and orexin-B neuropeptides produced in the lateral hypothalamus. These neuropeptides regulate:
Research has demonstrated connections between orexin signaling and neurodegenerative processes:
The theoretical rationale for using Daridorexant to prevent post-cardiotomy delirium includes:
Daridorexant works by blocking both orexin receptor types:
| Receptor | Role | Effect of Antagonism |
|---|---|---|
| OX1R (HCRTR1) | Arousal, stress response | Reduced stress-induced wakefulness |
| OX2R (HCRTR2) | Sleep-wake regulation, circadian entrainment | Enhanced sleep initiation and maintenance |
┌─────────────────────────────────────────────────────────────┐
│ DARIDOREANT MECHANISM │
├─────────────────────────────────────────────────────────────┤
│ │
│ ┌─────────────┐ ┌──────────────┐ ┌───────────────┐ │
│ │ Surgery │───▶│ Orexin │───▶│ Hyperarousal │ │
│ │ Stress │ │ Overactivity │ │ & Wakefulness│ │
│ └─────────────┘ └──────────────┘ └───────────────┘ │
│ │ │
│ ▼ │
│ ┌──────────────┐ │
│ │ DARIDOREANT │ │
│ │ Blockade │ │
│ └──────────────┘ │
│ │ │
│ ┌────────────────────┼────────────────────┐ │
│ ▼ ▼ ▼ │
│ ┌─────────────┐ ┌──────────────┐ ┌───────────────┐ │
│ │ Improved │ │ Reduced │ │ Enhanced │ │
│ │ Sleep │ │ Excitotoxic │ │ Glymphatic │ │
│ │ Quality │ │ Damage │ │ Clearance │ │
│ └─────────────┘ └──────────────┘ └───────────────┘ │
│ │ │ │ │
│ └────────────────────┴────────────────────┘ │
│ │ │
│ ▼ │
│ ┌─────────────────┐ │
│ │ DELIRIUM │ │
│ │ PREVENTION │ │
│ └─────────────────┘ │
└─────────────────────────────────────────────────────────────┘
| Measure | Instrument | Timepoint |
|---|---|---|
| Delirium incidence | DRS-R98 (Delirium Rating Scale) | Postoperative days 1-3 |
| Delirium severity | 3D-CAM (3-Minute Diagnostic Interview) | Postoperative days 1-3 |
| Measure | Instrument | Timepoint |
|---|---|---|
| Sleep quality | Richards-Campbell Sleep Questionnaire | Postoperative nights 1-3 |
While this trial targets post-cardiotomy delirium rather than Alzheimer's disease directly, it has significant implications for neurodegeneration research:
This trial represents a novel therapeutic approach combining:
If successful, this approach could be extended to:
Kang et al. Orexin receptor antagonism reduces amyloid-beta production. 2009. ↩︎ ↩︎
Ohno et al. Orexin and Alzheimer's disease. 2020. ↩︎
Inouye et al. Postoperative delirium and long-term cognitive decline. 2014. ↩︎
Sleep and clearance of metabolic waste in the brain. 2022. ↩︎