Intranasal Dexmedetomidine-Esketamine for Sleep and Cognition in Older Adults With Mild-to-Moderate Cognitive Impairment

May 20, 2026 updated by: Dong-Xin Wang, Peking University First Hospital

Impact of Intranasal Dexmedetomidine-esketamine on Sleep Quality and Cognitive Function in Older Adults With Mild-to-moderate Cognitive Impairment: a Randomized, Double-blind, and Placebo-controlled Trial

Sleep is crucial for maintaining brain function and clearing metabolic waste products (such as proteins associated with Alzheimer's disease) from the brain

. Continuous sleep disturbances may hinder this clearance process, thereby worsening cognitive impairment. This study aims to preliminarily explore whether a nasal spray combining dexmedetomidine and esketamine can safely and effectively improve sleep quality and cognitive function in older adults with mild-to-moderate cognitive impairment and comorbid sleep disorders.

The study plans to enroll 60 older adults (aged 60 and older) who experience both sleep disorders and mild-to-moderate cognitive impairment. Participants will be randomly assigned to one of two groups: half will receive the dexmedetomidine-esketamine combination nasal spray, and the other half will receive an equal volume of saline nasal spray (as a placebo). Both groups will receive the nasal spray twice a week for 4 consecutive weeks (8 treatments in total).

During each treatment session, a professional medical team will closely monitor participants' electrocardiogram (ECG), blood pressure, blood oxygen levels, and consciousness to ensure their safety. Additionally, participants will wear an actigraphy on the night of each treatment to objectively record their sleep patterns. Researchers will also conduct face-to-face follow-up visits at 1, 2, and 3 months after the treatment period ends to comprehensively evaluate improvements in sleep quality, cognitive function, mood, and activities of daily living. We hope this study will provide new treatment insights and options for improving the sleep and cognitive health of these patients.

Study Overview

Status

Not yet recruiting

Conditions

Intervention / Treatment

Study Type

Interventional

Enrollment (Estimated)

60

Phase

  • Not Applicable

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Contact

Study Contact Backup

Study Locations

  • China
      • Beijing, China, 100034
        • Peking University First Hospital
        • Contact:

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

  • Adult
  • Older Adult

Accepts Healthy Volunteers

No

Description

Inclusion Criteria:

  1. Age ≥ 60 years.
  2. Meeting the clinical diagnostic criteria for Alzheimer's disease, with mild cognitive impairment (MoCA score 18-25) or moderate cognitive impairment (MoCA score 10-17) due to Alzheimer's disease.
  3. Comorbid sleep disorder (Pittsburgh Sleep Quality Index [PSQI] score ≥ 7).
  4. Signed informed consent

Exclusion Criteria:

  1. Cognitive impairment/dementia due to other causes (e.g., vascular dementia, frontotemporal dementia, Parkinson's disease dementia).
  2. Unsuitable for intranasal administration due to nasal diseases (e.g., rhinitis, nasal polyps, or nasal congestion of any cause).
  3. Inability to communicate due to visual, auditory, speech, or other reasons, or Mini-Mental State Examination (MMSE) score ≤ 9 or MoCA score ≤ 9.
  4. History of schizophrenia, epilepsy, Parkinson's disease, or confirmed diagnosis of glaucoma, hyperthyroidism, pheochromocytoma, or myasthenia gravis.
  5. Confirmed diagnosis of restless legs syndrome, sleep apnea, or high risk for moderate-to-severe sleep apnea based on STOP-Bang assessment, or Body Mass Index (BMI) > 30 kg/m2.
  6. History of stroke or transient ischemic attack within 12 months prior to enrollment, confirmed intracranial aneurysm, or elevated intracranial pressure from any cause.
  7. Uncontrolled hypertension (e.g., hypertensive crisis or systolic blood pressure > 160 mmHg and/or diastolic blood pressure > 100 mmHg prior to enrollment), myocardial infarction, unstable angina, revascularization surgery within 12 months prior to enrollment, or NYHA class III.
  8. Sick sinus syndrome, severe sinus bradycardia (heart rate < 50 beats/min), atrioventricular block above degree II without a pacemaker, corrected QT interval (Fridericia-corrected QTcF) ≥ 450 ms, or other severe arrhythmias (e.g., frequent premature ventricular contractions).
  9. Uncontrolled diabetes (e.g., HbA1c > 9%, diabetic ketosis, hyperglycemic coma, or hypoglycemia).
  10. Severe hepatic dysfunction (Child-Pugh Class C), renal dysfunction (eGFR ≤ 30 ml/min/1.73m2), respiratory insufficiency (SpO2 < 93% on room air), or other severe diseases (e.g., frailty preventing independent walking, advanced-stage tumors).
  11. Alcohol or drug dependence (manifested as strong craving, uncontrolled use, and withdrawal symptoms upon cessation), or use of contraindicated medications.
  12. Major surgery under general anesthesia within 12 weeks prior to enrollment, or planned surgery within 12 weeks.
  13. Allergy to dexmedetomidine and/or esketamine.
  14. Participation in other interventional clinical studies.
  15. Any other conditions deemed unsuitable for study inclusion by the investigator.

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: Treatment
  • Allocation: Randomized
  • Interventional Model: Parallel Assignment
  • Masking: Quadruple

Arms and Interventions

Participant Group / Arm
Intervention / Treatment
Experimental: Intervention group
Participants in this arm will receive the intranasal dexmedetomidine-esketamine combination. The dosage is calculated based on body weight (approximately 0.4 μg/kg of dexmedetomidine and 0.2 mg/kg of esketamine). It is administered via a customized nasal spray device, alternating between both nostrils, every 5 minutes until the target dose is reached. This intervention is administered twice a week for 4 consecutive weeks (8 sessions in total).
Drug: Dexmedetomidine-esketamine combination
The experimental intervention is a combination of dexmedetomidine (approximately 0.4 μg/kg) and esketamine (approximately 0.2 mg/kg). The mixture is prepared using dexmedetomidine nasal spray and esketamine injection with normal saline. It is administered via a customized nasal spray device. The administration alternates between both nostrils every 5 minutes until the target dose is reached. Participants receive this intervention twice a week for 4 consecutive weeks, totaling 8 sessions
Placebo Comparator: Placebo group
Participants in this arm will receive an equal volume of normal saline as a placebo. The placebo is administered via the identical customized nasal spray device, following the exact same alternating nostril procedure, volume, and frequency as the intervention group (twice a week for 4 consecutive weeks, 8 sessions in total).
Drug: Placebo
The placebo intervention consists of an equal volume of 0.9% normal saline. It is prepared in the identical customized nasal spray device to match the appearance of the experimental drug. It is administered using the exact same alternating nostril procedure, volume, and frequency (twice a week for 4 consecutive weeks, totaling 8 sessions) as the intervention group.

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Change from baseline in Pittsburgh Sleep Quality Index (PSQI) score
Time Frame: 1 month post-intervention (Day 29)
The PSQI evaluates sleep quality. It consists of 7 components, and the total score ranges from 0 to 21. Higher scores indicate worse sleep quality.
1 month post-intervention (Day 29)

Secondary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Change from baseline in Montreal Cognitive Assessment (MoCA) score
Time Frame: 1, 2, and 3 months post-intervention (Days 29, 57, and 85)
The MoCA is a brief screening tool for assessing cognitive function. The total score ranges from 0 to 30. Higher scores indicate better cognitive function
1, 2, and 3 months post-intervention (Days 29, 57, and 85)
Change from baseline in Pittsburgh Sleep Quality Index (PSQI) score
Time Frame: 2 and 3 months post-intervention (Days 57 and 85)
The PSQI evaluates sleep quality. The total score ranges from 0 to 21, with higher scores indicating worse sleep quality
2 and 3 months post-intervention (Days 57 and 85)

Other Outcome Measures

Outcome Measure
Measure Description
Time Frame
Objective sleep parameters assessed by actigraphy
Time Frame: The night of each intervention (Days 1, 4, 8, 11, 15, 18, 22, and 25)
Objective sleep parameters, including Total Sleep Time (TST), Sleep Efficiency (SE), Sleep Latency (SL), and Wake After Sleep Onset (WASO), will be recorded continuously using a wearable wrist actigraphy device.
The night of each intervention (Days 1, 4, 8, 11, 15, 18, 22, and 25)
Subjective sleep quality assessed by Numeric Rating Scale (NRS)
Time Frame: The morning following each intervention (Days 2, 5, 9, 12, 16, 19, 23, and 26)
Subjective sleep quality is evaluated using an 11-point Numeric Rating Scale (NRS). The score ranges from 0 to 10, where 0 represents the "best sleep" and 10 represents the "worst sleep". Higher scores indicate worse subjective sleep quality.
The morning following each intervention (Days 2, 5, 9, 12, 16, 19, 23, and 26)
Change from baseline in Patient Health Questionnaire-9 (PHQ-9) score
Time Frame: 1, 2, and 3 months post-intervention (Days 29, 57, and 85)
The PHQ-9 assesses the severity of depression over the past two weeks. The total score ranges from 0 to 27. Higher scores indicate more severe depressive symptoms.
1, 2, and 3 months post-intervention (Days 29, 57, and 85)
Change from baseline in Activities of Daily Living (ADL) score
Time Frame: 1, 2, and 3 months post-intervention (Days 29, 57, and 85)
The ADL scale evaluates the physical and instrumental activities of daily living. The total score ranges from 14 to 56. Higher scores indicate less independence and greater functional impairment.
1, 2, and 3 months post-intervention (Days 29, 57, and 85)

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

Peking University First Hospital

Investigators

  • Principal Investigator: Dongxin Wang, MD, Peking University First Hospital

Publications and helpful links

The person responsible for entering information about the study voluntarily provides these publications. These may be about anything related to the study.

General Publications

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start (Estimated)

June 1, 2026

Primary Completion (Estimated)

November 1, 2027

Study Completion (Estimated)

December 1, 2027

Study Registration Dates

First Submitted

May 20, 2026

First Submitted That Met QC Criteria

May 20, 2026

First Posted (Actual)

May 27, 2026

Study Record Updates

Last Update Posted (Actual)

May 27, 2026

Last Update Submitted That Met QC Criteria

May 20, 2026

Last Verified

May 1, 2026

More Information

Terms related to this study

Additional Relevant MeSH Terms

Other Study ID Numbers

  • 2026-1064

Plan for Individual participant data (IPD)

Plan to Share Individual Participant Data (IPD)?

NO

Drug and device information, study documents

Studies a U.S. FDA-regulated drug product

No

Studies a U.S. FDA-regulated device product

No

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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