Intranasal Dexmedetomidine-esketamine on Sleep and Cognition in Older Adults With Mild-to-moderate Cognitive Impairment
28. maj 2026 opdateret af: 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
Patients with cognitive decline are frequently comorbid with sleep disorders which may in turn aggravate cognitive decline.
Sedative dose dexmedetomidine improved sleep quality but incresed bradycardia and hypotension; low dose dexmedetomidine produce less side effects, but the sleep promoting effects are relatively weak.
Low dose esketamine also has sleep-promoting effects but may produce neuropsychiatric side effects.
Both dexmedetomidine and esketamine are approved for intranasal administration.
We suppose that intranasal administration of dexmedetomidine-esketamine combination may improve sleep quality and therefore cognitive function in older ptients with Alzheimer's disease cognitive impairment and sleep disorders.
Studieoversigt
Status
Ikke rekrutterer endnu
Intervention / Behandling
Detaljeret beskrivelse
Along with aging population, the number of older adults with cognitive decline (such as Alzheimer's disease) is also increasing and constitutes a great challenge to public health. Normal sleep is important for maintaining both physical and mental health. However, patients with cognitive decline are frequently comorbid with sleep disorders which are associated with increased need of health care; sleep disorders may in turn aggravate cognitive decline in these patients.
Dexmedetomidine is a highly selective alpha 2-adrenoceptor agonist with sedative, anxiolytic, and analgesic effects. In previous studies, infusion of sedative dose dexmedetomidine improved sleep quality but incresed bradycardia and hypotension. Infusion of low dose dexmedetomidine is also effective in improving sleep quality with less side effects; however, the sleep promoting effects are relatively weak. Intranasal dexmedetomidine provides a non-invasive intervention and is used for sleep promotion in preoperative patients, but requires hemodynaamic monitoring due to potential side effects.
Ketamine is a noncompetitive N-Methyl-D-aspartic acid (NMDA) receptor antagonist and has been used as a dissociative anesthetic for decades. Esketamine is the S-enantiomer and has approximately twice the potency of ketamine. Recent studies showed that low dose esketamine also has anti-depressive and sleep-promoting effects. Intranasal esketamine has been approved for treatment-resistant depression, and is also used as premedication in children and to relieve postoperative pain in adults.
Even low dose ketamine/esketamine may produce neuropsychiatric side effects, which can be relieved by dexmedetomidine. A study in pediatric patients reported that intranasal co-administration of dexmedetomidine and esketamine produced synergetic effects on sedation. A study in adults showed that dexmedetomidine-esketamine combination as a supplement to patient-controlled opioid analgesia improved both analgesia and sleep quality without increasing side effects. A recent trial in older adults indicated that intranasal dexmedetomidine-esketamine improved neurocognitive recovery after surgery.
We suppose that intranasal administration of dexmedetomidine-esketamine combination may improve sleep quality and therefore cognitive function in older ptients with Alzheimer's disease cognitive impairment and sleep disorders.
Undersøgelsestype
Interventionel
Tilmelding (Anslået)
60
Fase
- Fase 4
Kontakter og lokationer
Dette afsnit indeholder kontaktoplysninger for dem, der udfører undersøgelsen, og oplysninger om, hvor denne undersøgelse udføres.
Studiekontakt
- Navn: Dong-Xin Wang, MD, PhD
- Telefonnummer: 010-83572784
- E-mail: wangdongxin@hotmail.com
Undersøgelse Kontakt Backup
- Navn: Jia-Hui Ma, PhD
- Telefonnummer: 010-83575085
- E-mail: mjh@bjmu.edu.cn
Studiesteder
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Beijing Municipality
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Beijing, Beijing Municipality, Kina, 100034
- Peking University First Hospital
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Kontakt:
- Dong-Xin Wang, MD, PhD
- Telefonnummer: 010-83572784
- E-mail: wangdongxin@hotmail.com
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Deltagelseskriterier
Forskere leder efter personer, der passer til en bestemt beskrivelse, kaldet berettigelseskriterier. Nogle eksempler på disse kriterier er en persons generelle helbredstilstand eller tidligere behandlinger.
Berettigelseskriterier
Aldre berettiget til at studere
- Voksen
- Ældre voksen
Tager imod sunde frivillige
Ingen
Beskrivelse
Inclusion Criteria:
- Aged ≥ 60 years.
- 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.
- Comorbid with sleep disorders (Pittsburgh Sleep Quality Index [PSQI] score ≥ 7).
- Signed informed consent.
Exclusion Criteria:
- Cognitive impairment/dementia due to other causes (e.g., vascular dementia, frontotemporal dementia, Parkinson's disease dementia).
- Unsuitable for intranasal administration due to nasal cavity diseases (e.g., rhinitis, nasal polyps, or nasal congestion of any cause).
- Inability to communicate due to visual, auditory, language, or other reasons, or Mini-Mental State Examination (MMSE) score ≤ 9 or MoCA score ≤ 9.
- History of schizophrenia, epilepsy, or Parkinson's disease, or confirmed diagnosis of glaucoma, hyperthyroidism, pheochromocytoma, or myasthenia gravis.
- Confirmed diagnosis of restless legs syndrome or sleep apnea, or judged to be at high risk of moderate-to-severe sleep apnea according to STOP-Bang score, or Body Mass Index (BMI) > 30 kg/m2.
- History of stroke or transient ischemic attack within 12 months prior to enrollment, confirmed intracranial aneurysm, or elevated intracranial pressure from any cause.
- 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.
- 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).
- Uncontrolled diabetes (e.g., HbA1c > 9%, diabetic ketosis, hyperglycemic coma, or hypoglycemia).
- 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 with inability to walk independently, advanced-stage tumors).
- Alcohol or drug dependence (manifested as strong cravings, uncontrolled use, and withdrawal symptoms upon cessation), or use of contraindicated medications.
- Major surgery under general anesthesia within 12 weeks prior to enrollment, or planned surgery within 12 weeks.
- Allergy to dexmedetomidine and/or esketamine.
- Participation in other interventional clinical studies.
- Any other conditions deemed unsuitable for study inclusion by the investigator.
Studieplan
Dette afsnit indeholder detaljer om studieplanen, herunder hvordan undersøgelsen er designet, og hvad undersøgelsen måler.
Hvordan er undersøgelsen tilrettelagt?
Design detaljer
- Primært formål: Behandling
- Tildeling: Randomiseret
- Interventionel model: Parallel tildeling
- Maskning: Firedobbelt
Våben og indgreb
Deltagergruppe / Arm |
Intervention / Behandling |
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Eksperimentel: Intervention group
Participants in this arm will receive intranasal administration of dexmedetomidine-esketamine combination. The dosage will be calculated based on body weight (approximately 0.4 μg/kg of dexmedetomidine and 0.2 mg/kg of esketamine). The mixture of study drugs will be administered via a nasal spray device, alternating between the two nostrils every 5 minutes, until the target dose is reached. The combination will be administered twice a week for 4 consecutive weeks (8 sessions in total). |
The dosage will be calculated based on body weight (approximately 0.4 μg/kg of dexmedetomidine and 0.2 mg/kg of esketamine).
The mixture of study drugs will be administered via a nasal spray device, alternating between the two nostrils every 5 minutes, until the target dose is reached.
The combination will be administered twice a week for 4 consecutive weeks (8 sessions in total).
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Placebo komparator: Placebo group
Participants in this arm will receive intranasal administration of placebo (normal sline). The dosage (volume) will be calculated based on body weight in the same way as that in the intervention group. The placebo (normal saline) will be administered via a nasal spray device, alternating between the two nostrils every 5 minutes, until the target dose is reached. The placebo will be administered twice a week for 4 consecutive weeks (8 sessions in total). |
The dosage (volume) will be calculated based on body weight in the same way as that in the intervention group.
The placebo (normal saline) will be administered via a nasal spray device, alternating between the two nostrils every 5 minutes, until the target dose is reached.
The placebo will be administered twice a week for 4 consecutive weeks (8 sessions in total).
Andre navne:
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Hvad måler undersøgelsen?
Primære resultatmål
Resultatmål |
Foranstaltningsbeskrivelse |
Tidsramme |
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Change in Pittsburgh Sleep Quality Index (PSQI) score from baseline to 1 month
Tidsramme: Up to day 29 post-intervention initiation
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Sleep quality will be assessed with the Pittsburgh Sleep Quality Index (PSQI) .
This is a self-report questionnaire including 7 components: subjective sleep quality, sleep latency, sleep duration, habitual sleep efficiency, sleep disturbances, use of sleeping medication, and daytime dysfunction.
Each component is scored from 0 to 3; the global score ranges from 0 to 21, with higher scores indicating worse sleep quality.
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Up to day 29 post-intervention initiation
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Sekundære resultatmål
Resultatmål |
Foranstaltningsbeskrivelse |
Tidsramme |
|---|---|---|
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Changes in Montreal Cognitive Assessment (MoCA) score from baseline to 1, 2, and 3 months
Tidsramme: Up to days 29, 57, and 85 post-intervention initiation
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Cognitive function will be assessed with the Montreal Cognitive Assessment (MoCA; scores range from 0 to 30, with higher scores indicating better function).
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Up to days 29, 57, and 85 post-intervention initiation
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Changes in Pittsburgh Sleep Quality Index (PSQI) score from baseline to 2 and 3 months
Tidsramme: Up to days 57 and 85 post-intervention initiation
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Sleep quality will be assessed with the Pittsburgh Sleep Quality Index (PSQI) .
This is a self-report questionnaire including 7 components: subjective sleep quality, sleep latency, sleep duration, habitual sleep efficiency, sleep disturbances, use of sleeping medication, and daytime dysfunction.
Each component is scored from 0 to 3; the global score ranges from 0 to 21, with higher scores indicating worse sleep quality.
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Up to days 57 and 85 post-intervention initiation
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Andre resultatmål
Resultatmål |
Foranstaltningsbeskrivelse |
Tidsramme |
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Objective sleep parameters assessed by actigraphy
Tidsramme: During the night after each intervention (days 1, 4, 8, 11, 15, 18, 22, and 25)
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Objective sleep parameters, including Total Sleep Time (TST), Sleep Efficiency (SE), Sleep Latency (SL), and Wake After Sleep Onset (WASO), will be monitored continuously using a wearable wrist actigraphy device.
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During the night after each intervention (days 1, 4, 8, 11, 15, 18, 22, and 25)
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Subjective sleep quality assessed by Numeric Rating Scale (NRS)
Tidsramme: The morning following each intervention (days 2, 5, 9, 12, 16, 19, 23, and 26)
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Subjective sleep quality will be 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".
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The morning following each intervention (days 2, 5, 9, 12, 16, 19, 23, and 26)
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Change in Patient Health Questionnaire-9 (PHQ-9) score from baseline to 1, 2, and 3 months
Tidsramme: Up to days 29, 57, and 85 post-intervention initiation
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Depression is assessed with the Patient Health Questionnaire-9 (PHQ-9).
The PHQ-9 includes 9-item requiring responses of 0 (not at all) to 3 (nearly every day) to assess the occurrence of depressive symptoms over the last two weeks.
It has 8 items on depressive symptoms and 1 focused on suicidal ideation.
Total scores range from 0 to 27, with higher score indicating more severe symptoms.
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Up to days 29, 57, and 85 post-intervention initiation
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Change in Activities of Daily Living (ADL) score from baseline to 1, 2, an 3 months
Tidsramme: Up to days 29, 57, and 85 post-intervention initiation
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The Activities of Daily Living (ADL) scale evaluates basic activities of daily living (BADL) and instrumental activities of daily living (IADL).
The total score ranges from 14 to 56, with higher scores indicating more severe impairment of daily living ability.
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Up to days 29, 57, and 85 post-intervention initiation
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Samarbejdspartnere og efterforskere
Det er her, du vil finde personer og organisationer, der er involveret i denne undersøgelse.
Sponsor
Efterforskere
- Ledende efterforsker: Dong-Xin Wang, MD, PhD, Peking University First Hospital
Publikationer og nyttige links
Den person, der er ansvarlig for at indtaste oplysninger om undersøgelsen, leverer frivilligt disse publikationer. Disse kan handle om alt relateret til undersøgelsen.
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Datoer for undersøgelser
Disse datoer sporer fremskridtene for indsendelser af undersøgelsesrekord og resumeresultater til ClinicalTrials.gov. Studieregistreringer og rapporterede resultater gennemgås af National Library of Medicine (NLM) for at sikre, at de opfylder specifikke kvalitetskontrolstandarder, før de offentliggøres på den offentlige hjemmeside.
Studer store datoer
Studiestart (Anslået)
1. juni 2026
Primær færdiggørelse (Anslået)
1. november 2027
Studieafslutning (Anslået)
1. december 2027
Datoer for studieregistrering
Først indsendt
20. maj 2026
Først indsendt, der opfyldte QC-kriterier
20. maj 2026
Først opslået (Faktiske)
27. maj 2026
Opdateringer af undersøgelsesjournaler
Sidste opdatering sendt (Faktiske)
1. juni 2026
Sidste opdatering indsendt, der opfyldte kvalitetskontrolkriterier
28. maj 2026
Sidst verificeret
1. maj 2026
Mere information
Begreber relateret til denne undersøgelse
Yderligere relevante MeSH-vilkår
- Neurologiske manifestationer
- Sygdomme i nervesystemet
- Psykiske lidelser
- Neurokognitive lidelser
- Kognitionsforstyrrelser
- Patologiske tilstande, tegn og symptomer
- Tegn og symptomer
- Kognitiv dysfunktion
- Søvnvågningsforstyrrelser
- Farmaceutiske præparater
- Krystalloidopløsninger
- Isotoniske løsninger
- Løsninger
- Salinopløsning
Andre undersøgelses-id-numre
- 2026-0208
Plan for individuelle deltagerdata (IPD)
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