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

NCT07800910 | Not Yet Recruiting Early Phase 1 FDA Drug

• 1 other identifier: 2026P001362
• Study Type: interventional
• Target: 12
• Locations: 1 country
• Sites: 2

Brief 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. 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.

Conditions

Sleep; Circadian Rhythm

Keywords

sleep; circadian rhythm; dexmedetomidine; older adults; sleep architecture; Phosphorylated Tau 217

Outcome Measures

Primary Outcomes (18)

• Number of Participants With Adverse Events

  Number of participants experiencing one or more adverse events during the study, including hypotension, bradycardia, and excessive sedation.

  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.

  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.

  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.

  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.

  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.

  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.

  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.

  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.

  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.

  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.

  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.

  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.

  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.

  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.

  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.

  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.

  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.

  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

  During the 3-hour dim-light period preceding habitual bedtime on each in-laboratory study day

• Sleep Latency Measured by Polysomnography

  Each night (Nights 1, 2, and 3) of each 3-night in-laboratory study period

• Total Sleep Time Measured by Polysomnography

  Each night (Nights 1, 2, and 3) of each 3-night in-laboratory study period

• Sleep Efficiency Measured by Polysomnography

  Each night (Nights 1, 2, and 3) of each 3-night in-laboratory study period

• Wake After Sleep Onset Measured by Polysomnography

  Each night (Nights 1, 2, and 3) of each 3-night in-laboratory study period

Other Outcomes (17)

• Plasma p-tau217 Concentrations Across the 24-Hour Sleep-Wake Cycle

  Across the 24-hour sleep-wake cycle during each in-laboratory study period

• Sleep Onset Time Measured by Wrist Actigraphy

  Days 1-7 of the pre-laboratory monitoring period and Days 1-10 of the post-laboratory ambulatory monitoring period during each study period

• Total Sleep Time Measured by Wrist Actigraphy

  Days 1-7 of the pre-laboratory monitoring period and Days 1-10 of the post-laboratory ambulatory monitoring period during each study period

Study Arms (2)

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.

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.

Drug: Dexmedetomidine sublingual film; Drug: Placebo Sublingual Film

Interventions

Dexmedetomidine sublingual film DRUG

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 First; Sublingual Dexmedetomidine First

Placebo Sublingual Film DRUG

Participants receive a matched placebo sublingual film identical in appearance, packaging, and administration method to the active dexmedetomidine formulation but containing no active medication.

Placebo First; Sublingual Dexmedetomidine First

Eligibility Criteria

• Age: 65 Years+
• Sex: all
• Healthy Volunteers: Yes
• Age Groups: Older Adult (65+)

You may qualify if:

• 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

You may not qualify if:

• 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

Sponsors & Collaborators

• Massachusetts General Hospital: lead
• Brigham and Women's Hospital: collaborator

Study Sites (2)

Brigham and Women's Hospital

Boston, Massachusetts, 02115, United States

Location

Massachusetts General Hospital

Boston, Massachusetts, 02129, United States

Location

Central Study Contacts

Chenlu Gao, PhD

CONTACT

617-643-9515; cgao6@mgh.harvard.edu

Study Design

• Study Type: interventional
• Phase: early phase 1
• Allocation: RANDOMIZED
• Masking: TRIPLE
• Who Masked: PARTICIPANT, INVESTIGATOR, OUTCOMES ASSESSOR
• Masking Details: All personnel interacting with the participants, administering the sublingual films, drawing the serial blood samples, and analyzing the physiological or biomarker data are kept fully unaware of the treatment sequence (whether the participant received 120 mcg of sublingual dexmedetomidine or the matched identical placebo film on Day 2 of a given study period). The randomization sequence is maintained securely by the MGH/BWH research pharmacy infrastructure and a trial statistician who is completely isolated from data collection and participant interaction.
• Purpose: SUPPORTIVE CARE
• Intervention Model: CROSSOVER
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Assistant Professor

Study Record Dates

• First Submitted: August 17, 2026
• First Posted: September 2, 2026
• Study Start: September 1, 2026
• Primary Completion (Estimated): August 31, 2028
• Study Completion (Estimated): August 31, 2028
• Last Updated: September 2, 2026

Record last verified: 2026-05

Data Sharing

• IPD Sharing: Will share
• Shared Documents: STUDY PROTOCOL, SAP
• Time Frame: Beginning 6 months after publication of the primary study results and available for 5 years.
• Access Criteria: Requests from qualified researchers will be considered for scientifically appropriate research purposes. Requests will be reviewed by the study investigators and/or institution, and access will be subject to applicable institutional requirements and execution of an appropriate data use agreement.

Locations

US (2)