Effect of Intranasal Negative Pressure Therapy on Cognitive Function in Patients With Mild Cognitive Impairment and Obstructive Sleep Apnea

The Efficacy and Safety of Intranasal Negative Pressure Therapy (iNAP) in Patients With Mild Cognitive Impairment Complicated With Obstructive Sleep Apnea: A Randomized Controlled Trial

This study is a randomized controlled trial with two phases: pre-trial and formal trial. The pre-trial will include 5 participants to observe the 4-week adherence (≥4 hours/night) and safety (adverse event rate) of the iNAP device. For the formal trial, 60 patients with MCI and moderate-to-severe OSA will be stratified and block randomized (by baseline AHI levels: 15-30 events/h vs >30 events/h) into either the iNAP intervention group (using the device nightly for 24 weeks) or the control group (receiving only sleep hygiene guidance). The primary outcome is the change in MoCA scores from baseline at week 24. Secondary outcomes include AHI reduction rate, sleep efficiency, plasma Aβ42/Aβ40 ratio, cognitive assessments, and brain imaging indicators. Follow-up visits will occur at baseline, week 12, and week 24 to monitor cognitive function, sleep parameters, and safety.

Study Overview

• Status: Not yet recruiting
• Conditions: Mild Cognitive Impairment (MCI)
• Intervention / Treatment: Device: Intranasal Negative Pressure

• Study Type: Interventional
• Enrollment (Estimated): 65
• Phase: Not Applicable

Contacts and Locations

• Study Contact: Name: Yi Tang; Phone Number: 00861083199456; Email: tangyi@xwhosp.org
• Study Contact Backup: Name: Liyang liu; Phone Number: 00861083192332; Email: liuliyang@xwhosp.org

Study Locations

• China
  • Beijing, China, 100053
    • Xuanwu Hospital, Capital Medical University
    • Contact: Liyang liu; Phone Number: 00861083192332; Email: liuliyang@xwhosp.org

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Adult; Older Adult
• Accepts Healthy Volunteers: No

Description

Inclusion Criteria:

1. Aged between 50 and 75 years, regardless of gender.
2. Diagnosed with moderate-to-severe obstructive sleep apnea (OSA) via polysomnography (PSG), with an Apnea-Hypopnea Index (AHI) ≥ 15 events/hour.
3. Neuropsychological assessment consistent with mild cognitive impairment (MCI), defined as a Clinical Dementia Rating (CDR) of 0.5 and a Montreal Cognitive Assessment (MoCA) score between 20 and 26.
4. Successful completion of the iNAP device adaptation test (no significant oral discomfort, nausea, or other adverse reactions after 30 minutes of wear).
5. If using cognitive-enhancing medications (e.g., cholinesterase inhibitors, memantine), stable doses must be maintained for at least 12 weeks prior to baseline.
6. Voluntary signing of the informed consent form and willingness to comply with follow-up procedures.

Exclusion Criteria:

1. History of allergy to silicone components of the iNAP device. Severe nasal obstructive diseases (e.g., nasal polyps, moderate-to-severe chronic rhinitis) that impair nasal breathing function.
2. Acute cardio-cerebrovascular events (e.g., myocardial infarction, cerebral infarction) or acute exacerbation of moderate-to-severe lung diseases (e.g., COPD exacerbation) within the past 6 months.
3. Comorbidities with other sleep disorders (e.g., primary insomnia, narcolepsy, restless legs syndrome) that may interfere with OSA assessment.
4. Diagnosis of central nervous system diseases (e.g., epilepsy, sequelae of encephalitis) or severe mental illness (e.g., schizophrenia, major depression with SDS ≥ 63 points).
5. Severe aphasia or physical disability precluding completion of neuropsychological assessments.
6. Presence of consciousness disturbance from any cause.
7. Current diagnosis of depression or psychiatric disorders.
8. History of alcoholism, drug addiction, or neurological diseases known to cause cognitive impairment (e.g., traumatic brain injury, epilepsy, encephalitis, normal pressure hydrocephalus).
9. Concurrent participation in other clinical trials.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: None (Open Label)

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: iNAP group; Participants use the iNAP device nightly for 24 weeks, combined with best support care.	Device: Intranasal Negative Pressure; No interventions have been assigned to arm 'iNAP group' Intervention 'Intranasal Negative Pressure' has not been assigned to an arm/group.
No Intervention: Control Group; Participants receive only sleep hygiene guidance without using the iNAP device.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Change in MoCA Score from Baseline to Week 24	Montreal Cognitive Assessment (MoCA) scale ranges from 0 to 30, and higher value represents a better outcome. This study will use MoCA to assess changes in the global cognitive function after intervention.	Baseline (Day7～0 days) and Week 24 (Day 168±7 days)

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
AHI Reduction Rate at Week 12 and Week 24	Percentage reduction in Apnea-Hypopnea Index (AHI) calculated as [(Baseline AHI - Follow-up AHI)/Baseline AHI] × 100%.	Baseline, Week 12 (Day 84±7 days), and Week 24
Change in Plasma Aβ42/Aβ40 Ratio	Alteration in the ratio of plasma amyloid-beta 42 to 42/40	Baseline, Week 12, and Week 24
Change in Minimum Oxygen Saturation (LSaO₂)	Increase in LSaO₂ from baseline, monitored via polysomnography (PSG)	Baseline, Week 12, and Week 24
Change in Sleep Efficiency	Improvement in sleep efficiency [(Total Sleep Time/Time in Bed) × 100%] assessed by PSG.	Baseline, Week 12, and Week 24
Change in Auditory Verbal Learning Test Scores	Auditory Verbal Learning Test (AVLT) scale ranges from 0 to 75 (sum of immediate recall and delayed recall), and higher value represents a better verbal memory. This study will use AVLT to assess changes in the episodic memory after intervention.	Baseline, Week 12, and Week 24
Changes in Plasma P-tau217 Concentrations	Reductions in plasma phosphorylated tau 217 (P-tau217) concentrations.	Baseline, Week 12, Week 24
Changes in Structural MRI (sMRI) Metrics	Alterations in brain structure measured by T1-weighted sMRI.	Baseline, Week 12, Week 24
Changes in Diffusion Tensor Imaging (DTI) Metrics	Improvements in white matter microstructural integrity and perivascular space (PVS) status.	Baseline, Week 12, Week 24
Change in Resting-State fMRI (rs-fMRI) Brain Network Connectivity	Modifications in functional brain network connectivity compared to baseline.	Baseline, Week 12, Week 24
Changes in EEG Metrics	Alterations in electroencephalogram (EEG) parameters (e.g., spectral power, coherence).	Baseline, Week 12, Week 24
Changes in HAMA Score	Hamilton Anxiety Scale (HAMA) scale ranges from 0 to 56, and higher value represents more severe anxiety symptoms. This study will use HAMA to assess changes in the anxiety status after intervention.	Baseline, Week 12, Week 24
Changes in HAMD Score	Hamilton Depression Scale (HAMD) scale ranges from 0 to 52, and higher value represents more severe depressive symptoms. This study will use HAMD to assess changes in the depressive status after intervention.	Baseline, Week 12, Week 24
Incidence of Adverse Events (AEs) and Serious Adverse Events (SAEs)	Rate of treatment-related AEs (e.g., tongue soreness, increased salivation, dry mouth) and SAEs throughout the intervention period	Baseline, Week 12, Week 24
change in Trail Making Test	Trail Making Test (TMT) scale is quantified by completion time, and shorter time represents better executive function. This study will use TMT to assess changes in the cognitive flexibility and processing speed after intervention.	Baseline, week 12, and week 24
change in Stroop Color-Word Test	Stroop Color-Word Test (SCWT) scale is quantified by interference score (reaction time of conflict trials minus reaction time of non-conflict trials), and smaller value represents better inhibitory control. This study will use SCWT to assess changes in the executive function after intervention.	Baseline, week 12, and week 24
Change in plasma Neurofilament Light Chain	alterations in plasma Neurofilament Light Chain concentrations	baseline, week 12, and week 24
changes in plasma Glial Fibrillary Acidic Protein concentrations	changes in plasma Glial Fibrillary Acidic Protein concentrations	baseline, week 12, and week 24

Collaborators and Investigators

• Sponsor: Xuanwu Hospital, Beijing

Study record dates

Study Major Dates

• Study Start (Estimated): January 15, 2026
• Primary Completion (Estimated): December 31, 2026
• Study Completion (Estimated): December 31, 2026

Study Registration Dates

• First Submitted: January 9, 2026
• First Submitted That Met QC Criteria: January 19, 2026
• First Posted (Actual): January 20, 2026

Study Record Updates

• Last Update Posted (Actual): January 20, 2026
• Last Update Submitted That Met QC Criteria: January 19, 2026
• Last Verified: January 1, 2026

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Mental Disorders; Neurocognitive Disorders; Cognition Disorders; Cognitive Dysfunction
• Other Study ID Numbers: 2025433; LinYanShen [2025] No.433-002 (Other Identifier: Xuanwu Hospital Capital Medical University)

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