SleepEarly Phase 1DEXTERNCT07800910
Dexmedetomidine Trial for Effects on Rhythms, Sleep Architecture, and Biomarker Dynamics in Older Adults
A Early Phase 1 study testing Dexmedetomidine sublingual film in people with Sleep and Circadian Rhythm, run by Massachusetts General Hospital at 2 sites in United States.
Trial summary
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. Read more about this study
- Who is it for?
- Ages 65 years and olderHealthy volunteers can take part
- Conditions the study is for
- Sleep, Circadian Rhythm
- What is being tested?
- Dexmedetomidine sublingual film
- Could I receive a placebo?
- Yes, some participants may receive a placebo
- How many people
- 12 participants
- Where
- 2 sitesUnited States
- Study dates
- 1 Sep 2026to 31 Aug 2028
- Phase
- Early Phase 1
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 65 years and older
- All sexes
- Healthy volunteers accepted
- Older adult
Who may be able to join
- 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
Who cannot join
- 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
Show all 19Show fewer
- 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
Trial locations and contacts
2 sites in 1 country. Contact the study team or a site near you to ask about taking part.
United States2 sites
Brigham and Women's Hospital
Boston, Massachusetts, 02115
Peng Li, PhD, 617-643-9514, pli9@mgh.harvard.edu
Massachusetts General Hospital
Boston, Massachusetts, 02129
About this study
Official title: Dexmedetomidine Trial for Effects on Rhythms, Sleep Architecture, and Biomarker Dynamics - A Pilot Study (DEXTER)
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.
Read the detailed description
Circadian rhythms are fundamental regulators of human physiology, coordinating sleep-wake timing, neural activity, metabolic processes, and hormonal signaling across the 24-hour day. These endogenous rhythms are coordinated by the suprachiasmatic nucleus (SCN), the central circadian pacemaker in the hypothalamus that integrates environmental cues such as light to synchronize peripheral and central biological processes. In older adults, circadian rhythms often degrade, exhibiting reduced robustness and impaired alignment with behavioral cycles. Such alterations are closely linked to disrupted sleep architecture, particularly sleep fragmentation and loss of restorative non-rapid eye movement (NREM) sleep. Crucially, sleep and circadian dysfunction is increasingly recognized as a critical modulator of neurodegenerative biomarker dynamics. Experimental evidence suggests that fragmented sleep and reduced slow-wave sleep directly alter the production, release, and clearance of neurotoxic proteins, leading to elevated tau levels. These observations highlight a potential mechanistic pathway linking sleep-circadian dysfunction to neurodegeneration and underscore the need to understand how interventions that stabilize these systems influence the temporal profile of tau-related biomarkers. Dexmedetomidine, a highly selective alpha2-adrenergic receptor agonist, represents a unique pharmacologic probe for investigating the links between sleep architecture, circadian physiology, and tau biomarker dynamics. Unlike traditional sedatives, dexmedetomidine engages endogenous sleep-promoting pathways and produces a NREM-like state characterized by electrophysiologic features resembling natural sleep. Beyond its sleep-modulating properties, emerging preclinical evidence suggests that dexmedetomidine exerts potent chronobiotic effects (i.e., the ability to stabilize or entrain circadian rhythms). For instance, preclinical models indicate it activates vasoactive intestinal peptide (VIP) neurons within the SCN and modulates circadian entrainment processes. Clinical studies of thoracic surgery patients further suggest that dexmedetomidine may preserve endogenous circadian signaling, such as melatonin secretion, during the early postoperative period. The recent development of sublingual dexmedetomidine (SL Dex) provides a transformative, noninvasive formulation that enables controlled administration outside of intensive care settings, distinguishing it from traditional intravenous (IV) dexmedetomidine, which is typically limited to monitored environments. Preliminary studies have suggested that SL Dex produces measurable changes in sleep architecture, including increased slow-wave activity, shortened sleep latency, and prolonged REM sleep latency. However, the extent to which SL Dex influences circadian regulation, sleep architecture, and the temporal profile of tau biomarkers across the 24-hour sleep-wake cycle in humans has not been systematically characterized. Addressing this gap requires a rigorously controlled experimental approach capable of isolating the physiologic effects of SL Dex from environmental and behavioral confounders. Prior clinical studies have largely occurred in perioperative or other medically complex settings in which surgery, pain, inflammation, environmental disruption, concomitant medications, and irregular behaviors may confound interpretation of sleep and circadian outcomes. An in-laboratory protocol that standardizes light exposure, posture, feeding, activity, and sampling timing provides a necessary platform to isolate these effects. Determining whether SL Dex produces not only sleep-like sedation, but also measurable sleep/circadian effects and tau dynamics would provide important insights into the relationship between pharmacologic modulation of sleep-circadian biology and inform future translational studies in aging and neurobiology.
Specific Aims and Objectives: This study aims to evaluate the feasibility, safety, and physiologic effects of sublingual dexmedetomidine (SL Dex) on sleep architecture, circadian physiology, and tau biomarker dynamics in older adults under controlled laboratory conditions. SL Dex represents a novel, noninvasive approach to modulating sleep and circadian biology and provides a unique opportunity to examine downstream effects on neurodegenerative biomarkers. Specifically, this study aims to:
- Assess the feasibility and safety of administering SL Dex within a controlled in-laboratory sleep and circadian protocol with ambulatory follow-up.
- Quantify the acute effects of SL Dex on sleep architecture, circadian physiology, and tau dynamics under controlled experimental conditions.
- Characterize the duration and trajectory of SL Dex-associated effects on sleep and circadian physiology during ambulatory follow-up.
- Conditions
- Sleep, Circadian Rhythm
- Being tested
- Dexmedetomidine sublingual film, Placebo Sublingual Film
- Keywords
- sleep, circadian rhythm, dexmedetomidine, older adults, sleep architecture, Phosphorylated Tau 217
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Dexmedetomidine sublingual filmDrug
Participants receive a single 120 mcg dose of sublingual dexmedetomidine (IGALMI®) administered approximately 15-20 minutes before the scheduled sleep opportunity during the in-laboratory protocol.
Placebo Sublingual FilmDrug
Participants receive a matched placebo sublingual film identical in appearance, packaging, and administration method to the active dexmedetomidine formulation but containing no active medication.
| Study group | Role | What they receive |
|---|---|---|
| Sublingual Dexmedetomidine First | Experimental | Participants receive a single 120 mcg dose of sublingual dexmedetomidine (IGALMI®) during the first in-laboratory study period and matched placebo during the second study period after a washout interval of at least 3 weeks. The study evaluates effects on sleep architecture, circadian physiology, and plasma tau biomarker dynamics under controlled laboratory conditions. Receives: Drug: Dexmedetomidine sublingual film; Drug: Placebo Sublingual Film |
| Placebo First | Placebo comparator | Participants receive matched placebo during the first in-laboratory study period and a single 120 mcg dose of sublingual dexmedetomidine (IGALMI®) during the second study period after a washout interval of at least 3 weeks. The study evaluates effects on sleep architecture, circadian physiology, and plasma tau biomarker dynamics under controlled laboratory conditions. Receives: Drug: Dexmedetomidine sublingual film; Drug: Placebo Sublingual Film |
What is being measured
The primary outcome is the main question the study is designed to answer.
Number of Participants With Adverse Events
Number of participants experiencing one or more adverse events during the study, including hypotension, bradycardia, and excessive sedation.
Measured: From first study intervention through completion of the 10-day ambulatory follow-up following the second study period
Proportion of Participants Completing the Study
Proportion of enrolled participants who complete both study periods, including the in-laboratory protocols and post-laboratory ambulatory follow-up.
Measured: Through completion of the 10-day ambulatory follow-up following the second study period
Proportion of Consented Participants Who Are Randomized
Proportion of participants who provide informed consent and are subsequently randomized to a study intervention sequence, calculated as the number of randomized participants divided by the total number of participants who provide informed consent.
Measured: At randomization, prior to the first study intervention
Proportion of Participants Completing the In-Laboratory Protocol
Proportion of enrolled participants who complete the 3-night in-laboratory protocol during both study periods.
Measured: Through completion of the second 3-night in-laboratory study period
Proportion of Participants Completing Ambulatory Follow-Up
Proportion of enrolled participants who complete the 10-day post-laboratory ambulatory monitoring period during both study periods.
Measured: Through completion of the 10-day ambulatory follow-up following the second study period
Proportion of Required Actigraphy Monitoring Completed
Proportion of required actigraphy monitoring completed by participants across the pre-laboratory and post-laboratory ambulatory monitoring periods.
Measured: Through completion of the 10-day ambulatory follow-up following the second study period
Proportion of Required Polysomnography Assessments Completed
Proportion of required in-laboratory polysomnography assessments completed by participants.
Measured: Through completion of the second 3-night in-laboratory study period
Proportion of Required Wearable EEG Assessments Completed
Proportion of required ambulatory wearable EEG assessments completed by participants.
Measured: Through completion of the 10-day ambulatory follow-up following the second study period
Proportion of Required Sleep Diaries Completed
Proportion of required sleep diary assessments completed by participants during ambulatory monitoring.
Measured: Through completion of the 10-day ambulatory follow-up following the second study period
Number of Participants Withdrawing Due to Adverse Effects
Number of participants who withdraw from the study or discontinue study procedures because of adverse effects.
Measured: From first study intervention through completion of the 10-day ambulatory follow-up following the second study period
Heart Rate Before and After Study Drug Administration
Heart rate measured before and after administration of sublingual dexmedetomidine or placebo to assess hemodynamic safety and tolerability. Heart rate will be reported in beats per minute.
Measured: Pre-dose and post-dose on Day 2 of each 3-day in-laboratory study period
Systolic Blood Pressure Before and After Study Drug Administration
Systolic blood pressure measured before and after administration of sublingual dexmedetomidine or placebo to assess hemodynamic safety and tolerability. Systolic blood pressure will be reported in mm Hg.
Measured: Pre-dose and post-dose on Day 2 of each 3-day in-laboratory study period
Diastolic Blood Pressure Before and After Study Drug Administration
Diastolic blood pressure measured before and after administration of sublingual dexmedetomidine or placebo to assess hemodynamic safety and tolerability. Diastolic blood pressure will be reported in mm Hg.
Measured: Pre-dose and post-dose on Day 2 of each 3-day in-laboratory study period
Proportion of Required Blood Samples Collected
Proportion of protocol-specified blood samples successfully collected during the in-laboratory study periods.
Measured: Through completion of the second 3-night in-laboratory study period
Number of Participants Unable to Complete a Study Procedure Due to Intolerance
Number of participants who are unable to complete one or more protocol-specified study procedures because of intolerance, including blood draws or physiologic monitoring procedures.
Measured: From enrollment through completion of the 10-day ambulatory follow-up following the second study period
Proportion of Required Core Body Temperature Capsule Assessments Completed
Proportion of required core body temperature assessments using the ingestible telemetry capsule that are completed by participants across the pre-laboratory, in-laboratory, and post-laboratory monitoring periods.
Measured: Pre-laboratory Day 6, continuously during the 3-day in-laboratory protocol, and post-laboratory Days 4 and 6 during each study period
Proportion of Participants Adherent to Required Caffeine Restrictions
Proportion of participants who adhere to protocol-specified caffeine restrictions during required study monitoring periods.
Measured: From 72 hours before admission through completion of the 3-night in-laboratory protocol during each study period
Proportion of Participants Adherent to Required Alcohol Restrictions
Proportion of participants who adhere to protocol-specified alcohol restrictions during required study monitoring periods.
Measured: From 24 hours before admission through completion of the 3-night in-laboratory protocol during each study period
Secondary outcomes (31)
Dim Light Melatonin Onset (DLMO) timing
Circadian phase assessed using dim light melatonin onset derived from serial plasma melatonin sampling during controlled dim-light conditions.
Measured: During the 3-hour dim-light period preceding habitual bedtime on each in-laboratory study day
Sleep Latency Measured by Polysomnography
Sleep latency, defined as the time from lights out to sleep onset, measured by overnight polysomnography.
Measured: Each night (Nights 1, 2, and 3) of each 3-night in-laboratory study period
Total Sleep Time Measured by Polysomnography
Total time spent asleep during the overnight sleep period, measured by polysomnography and reported in minutes.
Measured: Each night (Nights 1, 2, and 3) of each 3-night in-laboratory study period
Sleep Efficiency Measured by Polysomnography
Sleep efficiency measured by polysomnography, calculated as total sleep time divided by time in bed multiplied by 100 and reported as a percentage.
Measured: Each night (Nights 1, 2, and 3) of each 3-night in-laboratory study period
Wake After Sleep Onset Measured by Polysomnography
Total time spent awake after initial sleep onset and before final awakening, measured by polysomnography and reported in minutes.
Measured: Each night (Nights 1, 2, and 3) of each 3-night in-laboratory study period
REM Sleep Latency Measured by Polysomnography
Time from sleep onset to the first epoch of rapid eye movement (REM) sleep, measured by polysomnography and reported in minutes.
Measured: Each night (Nights 1, 2, and 3) of each 3-night in-laboratory study period
Percentage of Total Sleep Time Spent in N2 Sleep Measured by Polysomnography
Percentage of total sleep time classified as stage N2 sleep based on polysomnography.
Measured: Each night (Nights 1, 2, and 3) of each 3-night in-laboratory study period
Percentage of Total Sleep Time Spent in N3 Sleep Measured by Polysomnography
Percentage of total sleep time classified as stage N3 sleep based on polysomnography.
Measured: Each night (Nights 1, 2, and 3) of each 3-night in-laboratory study period
Percentage of Total Sleep Time Spent in REM Sleep Measured by Polysomnography
Percentage of total sleep time classified as rapid eye movement (REM) sleep based on polysomnography.
Measured: Each night (Nights 1, 2, and 3) of each 3-night in-laboratory study period
Phase of the Core Body Temperature Circadian Rhythm
Circadian phase of the core body temperature rhythm derived from continuous core body temperature monitoring using a rectal thermistor
Measured: Continuously across the 3-day in-laboratory protocol during each study period
Amplitude of the Core Body Temperature Circadian Rhythm
Amplitude of the core body temperature rhythm derived from continuous core body temperature monitoring using a rectal thermistor.
Measured: Continuously across the 3-day in-laboratory protocol during each study period
Amplitude of the Melatonin Rhythm
Amplitude of the melatonin rhythm derived from serial plasma melatonin concentrations collected under controlled in-laboratory conditions.
Measured: Across the 3-day in-laboratory protocol during each study period
EEG Delta Oscillation Power
Delta-band EEG power derived from quantitative EEG spectral analysis during overnight polysomnography and reported in squared microvolts (µV²).
Measured: Each night (Nights 1, 2, and 3) of each 3-night in-laboratory study period
EEG Delta Oscillation Power Density
Delta-band EEG power spectral density derived from quantitative EEG spectral analysis during overnight polysomnography and reported in squared microvolts per hertz (µV²/Hz).
Measured: Each night (Nights 1, 2, and 3) of each 3-night in-laboratory study period
EEG Slow Oscillation Power
Slow-oscillation EEG power derived from quantitative EEG spectral analysis during overnight polysomnography and reported in squared microvolts (µV²).
Measured: Each night (Nights 1, 2, and 3) of each 3-night in-laboratory study period
EEG Theta Oscillation Power
Theta-band EEG power derived from quantitative EEG spectral analysis during overnight polysomnography and reported in squared microvolts (µV²).
Measured: Each night (Nights 1, 2, and 3) of each 3-night in-laboratory study period
EEG Alpha Oscillation Power
Alpha-band EEG power derived from quantitative EEG spectral analysis during overnight polysomnography and reported in squared microvolts (µV²).
Measured: Each night (Nights 1, 2, and 3) of each 3-night in-laboratory study period
EEG Beta Oscillation Power
Beta-band EEG power derived from quantitative EEG spectral analysis during overnight polysomnography and reported in squared microvolts (µV²).
Measured: Each night (Nights 1, 2, and 3) of each 3-night in-laboratory study period
EEG Sigma Oscillation Power During NREM Sleep
Sigma-band EEG power derived from quantitative EEG spectral analysis during non-rapid eye movement (NREM) sleep stages and reported in squared microvolts (µV²).
Measured: Each night (Nights 1, 2, and 3) of each 3-night in-laboratory study period
EEG Slow-Wave Amplitude
Mean amplitude of detected EEG slow waves derived from quantitative EEG analysis during overnight polysomnography and reported in microvolts (µV).
Measured: Each night (Nights 1, 2, and 3) of each 3-night in-laboratory study period
EEG Slow-Wave Slope
Mean slope of detected EEG slow waves derived from quantitative EEG analysis during overnight polysomnography and reported in microvolts per second (µV/s).
Measured: Each night (Nights 1, 2, and 3) of each 3-night in-laboratory study period
Sleep Spindle Density During NREM Sleep
Density of detected sleep spindles derived from quantitative EEG analysis during non-rapid eye movement (NREM) sleep stages and reported as the number of spindles per minute.
Measured: Each night (Nights 1, 2, and 3) of each 3-night in-laboratory study period
Sleep Spindle Frequency During NREM Sleep
Mean frequency of detected sleep spindles derived from quantitative EEG analysis during non-rapid eye movement (NREM) sleep stages and reported in hertz (Hz).
Measured: Each night (Nights 1, 2, and 3) of each 3-night in-laboratory study period
Sleep Spindle Duration During NREM Sleep
Mean duration of detected sleep spindles derived from quantitative EEG analysis during non-rapid eye movement (NREM) sleep stages and reported in seconds.
Measured: Each night (Nights 1, 2, and 3) of each 3-night in-laboratory study period
Sleep Spindle Amplitude During NREM Sleep
Mean amplitude of detected sleep spindles derived from quantitative EEG analysis during non-rapid eye movement (NREM) sleep stages and reported in microvolts (µV).
Measured: Each night (Nights 1, 2, and 3) of each 3-night in-laboratory study period
Time Spent in N1 Sleep Measured by Polysomnography
Total time classified as stage N1 sleep based on polysomnography and reported in minutes.
Measured: Each night (Nights 1, 2, and 3) of each 3-night in-laboratory study period
Time Spent in N2 Sleep Measured by Polysomnography
Total time classified as stage N2 sleep based on polysomnography and reported in minutes.
Measured: Each night (Nights 1, 2, and 3) of each 3-night in-laboratory study period
Time Spent in N3 Sleep Measured by Polysomnography
Total time classified as stage N3 (slow-wave) sleep based on polysomnography and reported in minutes.
Measured: Each night (Nights 1, 2, and 3) of each 3-night in-laboratory study period
Time Spent in REM Sleep Measured by Polysomnography
Total time classified as rapid eye movement (REM) sleep based on polysomnography and reported in minutes.
Measured: Each night (Nights 1, 2, and 3) of each 3-night in-laboratory study period
EEG Slow-Wave Density
Density of detected EEG slow waves derived from quantitative EEG analysis during overnight polysomnography and reported as the number of slow waves per minute.
Measured: Each night (Nights 1, 2, and 3) of each 3-night in-laboratory study period
Percentage of Total Sleep Time Spent in N1 Sleep Measured by Polysomnography
Percentage of total sleep time classified as stage N1 sleep based on polysomnography.
Measured: Each night (Nights 1, 2, and 3) of each 3-night in-laboratory study period
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted2 Sep 2026
- Study start1 Sep 2026 (estimated)
- Primary completion31 Aug 2028 (estimated)
- Study completion31 Aug 2028 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for SleepStudies of the same condition, open and under way.
- More trials run by Massachusetts General HospitalThe sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Early Phase 1
- Primary purpose
- Supportive care
- Allocation
- Randomised
- Intervention model
- Crossover
- Masking
- Triple blind
- Who is masked
- Participant, Investigator, Outcomes assessor
- Enrolment
- 12 participants (estimated)
Sponsor and investigators
- Lead sponsor
- Massachusetts General Hospital
- Sponsor type
- University, hospital or other
- Collaborators
- Brigham and Women's Hospital
- Responsible party
- Principal investigator, Peng Li, Massachusetts General Hospital
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT07800910
- Sponsor's protocol ID
- 2026P001362
- Acronym
- DEXTER
- Status last verified
- May 2026
- First submitted
- 17 Aug 2026
- Last updated
- 2 Sep 2026
- Results posted
- No
- Data monitoring committee
- No
- FDA-regulated drug
- Yes
- FDA-regulated device
- No
- Individual data sharing
- Yes: De-identified individual participant data that underlie the results reported in publications from this study may be made available to qualified researchers upon reasonable request, subject to applicable institutional, IRB, and data-sharing requirements.