Intranasal Dexmedetomidine-esketamine on Sleep and Cognition in Older Adults With Mild-to-moderate Cognitive Impairment
28 mai 2026 mis à jour par: 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.
Aperçu de l'étude
Statut
Pas encore de recrutement
Les conditions
Intervention / Traitement
Description détaillée
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.
Type d'étude
Interventionnel
Inscription (Estimé)
60
Phase
- Phase 4
Contacts et emplacements
Cette section fournit les coordonnées de ceux qui mènent l'étude et des informations sur le lieu où cette étude est menée.
Coordonnées de l'étude
- Nom: Dong-Xin Wang, MD, PhD
- Numéro de téléphone: 010-83572784
- E-mail: wangdongxin@hotmail.com
Sauvegarde des contacts de l'étude
- Nom: Jia-Hui Ma, PhD
- Numéro de téléphone: 010-83575085
- E-mail: mjh@bjmu.edu.cn
Lieux d'étude
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Beijing Municipality
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Beijing, Beijing Municipality, Chine, 100034
- Peking University First Hospital
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Contact:
- Dong-Xin Wang, MD, PhD
- Numéro de téléphone: 010-83572784
- E-mail: wangdongxin@hotmail.com
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-
Critères de participation
Les chercheurs recherchent des personnes qui correspondent à une certaine description, appelée critères d'éligibilité. Certains exemples de ces critères sont l'état de santé général d'une personne ou des traitements antérieurs.
Critère d'éligibilité
Âges éligibles pour étudier
- Adulte
- Adulte plus âgé
Accepte les volontaires sains
Non
La description
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.
Plan d'étude
Cette section fournit des détails sur le plan d'étude, y compris la façon dont l'étude est conçue et ce que l'étude mesure.
Comment l'étude est-elle conçue ?
Détails de conception
- Objectif principal: Traitement
- Répartition: Randomisé
- Modèle interventionnel: Affectation parallèle
- Masquage: Quadruple
Armes et Interventions
Groupe de participants / Bras |
Intervention / Traitement |
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Expérimental: 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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Comparateur placebo: 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).
Autres noms:
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Que mesure l'étude ?
Principaux critères de jugement
Mesure des résultats |
Description de la mesure |
Délai |
|---|---|---|
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Change in Pittsburgh Sleep Quality Index (PSQI) score from baseline to 1 month
Délai: 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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Mesures de résultats secondaires
Mesure des résultats |
Description de la mesure |
Délai |
|---|---|---|
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Changes in Montreal Cognitive Assessment (MoCA) score from baseline to 1, 2, and 3 months
Délai: 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
Délai: Up to days 57 and 85 post-intervention initiation
|
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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Autres mesures de résultats
Mesure des résultats |
Description de la mesure |
Délai |
|---|---|---|
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Objective sleep parameters assessed by actigraphy
Délai: 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)
Délai: 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
Délai: 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
Délai: 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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Collaborateurs et enquêteurs
C'est ici que vous trouverez les personnes et les organisations impliquées dans cette étude.
Parrainer
Les enquêteurs
- Chercheur principal: Dong-Xin Wang, MD, PhD, Peking University First Hospital
Publications et liens utiles
La personne responsable de la saisie des informations sur l'étude fournit volontairement ces publications. Il peut s'agir de tout ce qui concerne l'étude.
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Dates d'enregistrement des études
Ces dates suivent la progression des dossiers d'étude et des soumissions de résultats sommaires à ClinicalTrials.gov. Les dossiers d'étude et les résultats rapportés sont examinés par la Bibliothèque nationale de médecine (NLM) pour s'assurer qu'ils répondent à des normes de contrôle de qualité spécifiques avant d'être publiés sur le site Web public.
Dates principales de l'étude
Début de l'étude (Estimé)
1 juin 2026
Achèvement primaire (Estimé)
1 novembre 2027
Achèvement de l'étude (Estimé)
1 décembre 2027
Dates d'inscription aux études
Première soumission
20 mai 2026
Première soumission répondant aux critères de contrôle qualité
20 mai 2026
Première publication (Réel)
27 mai 2026
Mises à jour des dossiers d'étude
Dernière mise à jour publiée (Réel)
1 juin 2026
Dernière mise à jour soumise répondant aux critères de contrôle qualité
28 mai 2026
Dernière vérification
1 mai 2026
Plus d'information
Termes liés à cette étude
Termes MeSH pertinents supplémentaires
- Manifestations neurologiques
- Maladies du système nerveux
- Les troubles mentaux
- Troubles neurocognitifs
- Troubles cognitifs
- Conditions pathologiques, signes et symptômes
- Signes et symptômes
- Dysfonctionnement cognitif
- Troubles du sommeil et de l'éveil
- Préparations pharmaceutiques
- Solutions cristalloïdes
- Solutions isotoniques
- Solutions
- Solution saline
Autres numéros d'identification d'étude
- 2026-0208
Plan pour les données individuelles des participants (IPD)
Prévoyez-vous de partager les données individuelles des participants (DPI) ?
NON
Informations sur les médicaments et les dispositifs, documents d'étude
Étudie un produit pharmaceutique réglementé par la FDA américaine
Non
Étudie un produit d'appareil réglementé par la FDA américaine
Non
Ces informations ont été extraites directement du site Web clinicaltrials.gov sans aucune modification. Si vous avez des demandes de modification, de suppression ou de mise à jour des détails de votre étude, veuillez contacter register@clinicaltrials.gov. Dès qu'un changement est mis en œuvre sur clinicaltrials.gov, il sera également mis à jour automatiquement sur notre site Web .