Clinical TrialParallelNeurocognitive DisordersEsketaminePlaceboNot yet recruiting

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

This randomised, double-blind, placebo-controlled trial (n=60) will assess whether an intranasal dexmedetomidine-esketamine combination improves sleep quality and cognitive function in older adults aged 60 years and above with mild-to-moderate cognitive impairment and comorbid sleep disorder. The main aim is to evaluate change in Pittsburgh Sleep Quality Index (PSQI) score 1 month after the intervention. Participants will receive either the dexmedetomidine-esketamine nasal spray, calculated at approximately 0.4 μg/kg of dexmedetomidine plus 0.2 mg/kg of esketamine, or an equal volume of 0.9% normal saline placebo. Administration uses a customised nasal spray device with alternating nostrils every 5 minutes until the target dose is reached, given twice a week for 4 consecutive weeks (8 sessions in total). Safety monitoring during treatment includes ECG, blood pressure, blood oxygen levels and consciousness, and sleep will be recorded by actigraphy on treatment nights, with face-to-face follow-up at 1, 2 and 3 months after treatment to assess sleep, cognition, mood and activities of daily living.

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Target Enrollment
60 participants
Study Type
Phase NA interventional
Design
Randomized, quadruple Blind

Detailed Description

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 Arms & Interventions

Intervention group

experimental

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).

Interventions

  • Esketamine0.4 mcg
    via Other• twice a week for 4 consecutive weeks• 8 doses total

Placebo group

inactive

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).

Interventions

  • Placebo
    via Other• twice a week for 4 consecutive weeks• 8 doses total

Participants

Ages
60 – ?
Sexes
Male & Female

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 Details

  • Status
    Not yet recruiting
  • Phase
    Phase NA
  • Type
    interventional
  • Design
    Randomizedquadruple Blind
  • Target Enrollment60 participants
  • Timeline
    Start: 2026-06-01
    End: 2027-12-01
  • Compounds
    EsketaminePlacebo
  • Topic
    Neurocognitive Disorders

Study Team

Sponsors & Collaborators

Locations

Peking University First Hospital — Beijing, China