Dexmedetomidine Trial for Effects on Rhythms, Sleep Architecture, and Biomarker Dynamics in Older Adults

The DEXTER study is a cross-over, double-blind, placebo-controlled pilot research study led by Dr. Peng Li. The goal of this project is to evaluate the safety, feasibility, and biological effects of a single dose of sublingual (under-the-tongue) dexmedetomidine (SL Dex) in older adults. Specifically, researchers want to see how this medication affects sleep patterns, internal 24-hour circadian rhythms, and the daily cycles of certain neurological proteins (specifically plasma p-tau217) associated with brain aging.

Inclusion Criteria: * Age 65 years or older * Able to provide informed consent * Willing and able to comply with all study procedures, including in-laboratory and ambulatory monitoring * Able to provide informed consent using an IRB-approved translated consent document (when available) and complete study procedures with translated materials and/or qualified interpreter services, if needed- Stable residence and sleep schedule sufficient to complete study monitoring periods * Able to safely discontinue or adjust medications that may interfere with study procedures or outcomes, as determined by the study investigator Exclusion Criteria: * Clinically significant sleep disorders including narcolepsy, severe obstructive sleep apnea, REM sleep behavior disorder, or periodic limb movement disorder * Clinically significant cardiovascular disease including bradyarrhythmia, conduction abnormalities, heart failure, cardiomyopathy, ischemic heart disease, or conditions increasing risk with dexmedetomidine * Known QT prolongation, clinically significant arrhythmias, symptomatic bradycardia, hypokalemia, hypomagnesemia, or concurrent use of QT-prolonging medications * Contraindication or allergy to dexmedetomidine or study medications * Severe hepatic impairment * Neurologic, psychiatric, or substance use disorders that may interfere with participation or data interpretation * Use of medications significantly affecting sleep, circadian rhythms, or cardiovascular function * Gastrointestinal conditions increasing risk of capsule retention or bowel obstruction * Swallowing disorders or aspiration risk * Presence of implantable electronic medical devices * Use of anticoagulant or antiplatelet medications increasing bleeding risk * Pregnancy or breastfeeding * Shift work or frequent travel across more than two time zones * Participation in another interventional study that may interfere with study participation or interpretation of results * Anticipated need for MRI during the period in which the ingestible telemetry capsule may remain in the body * Inability to tolerate study procedures (blood draws, PSG, wearable devices, ingestible capsule) * Unable to provide informed consent even with translated materials/interpreter support * Previous participation in this trial * Concurrent interventional studies that may interfere with participation