Is Obstructive Sleep Apnea Important in the Development of Alzheimer's Disease?

NCT ID: NCT05094271

Last Updated: 2024-12-27

Study Results

Results pending

The study team has not published outcome measurements, participant flow, or safety data for this trial yet. Check back later for updates.

Basic Information

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Recruitment Status

RECRUITING

Clinical Phase

PHASE1

Total Enrollment

260 participants

Study Classification

INTERVENTIONAL

Study Start Date

2021-06-30

Study Completion Date

2025-05-20

Brief Summary

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Obstructive sleep apnea (OSA) is common in older adults and has recently been implicated in pathogenesis of Alzheimer's disease (AD). Research has shown that sleep disruptions have caused memory impairment. Sleep apnea is a form of sleep disruption. We would like to examine how obstructive sleep apnea may contribute to the progression of Alzheimer's disease.

Detailed Description

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Aim 1: We will assess the endotypes (mechanisms) underlying OSA in elderly individuals known to be high risk for AD (vs. non-OSA matched controls) using novel recently validated simplified techniques which do not require burdensome complex overnight experiments to assess endotypes (primary outcome loop gain). We will further assess the predicted response to O2 therapy in terms of respiratory outcomes among elderly OSA patients with varying levels of loop gain and pharyngeal collapsibility.

Hypothesis 1: A substantial proportion of high AD risk patients with OSA should be O2 responsive as predicted using pathophysiological assessments.

Aim 2: We will perform an overnight mechanistic study of oxygen therapy vs. room air in high AD risk patients with OSA (recruited from Aim 1 and others if necessary). Given the frequent intolerance of PAP in elderly patients, we anticipate that oxygen therapy may be a viable therapeutic approach in this fragile population. We will focus on respiratory outcomes (primary outcome: apnea hypopnea index) but also assess sleep dependent memory consolidation on word pairs task given the major impact in the elderly.

Hypothesis 2: O2, compared to room air, will improve OSA and neurocognitive outcomes in select elderly OSA patients at risk of AD.

Aim 3: Preclinical AD with OSA and non-OSA controls, from Aim 1 will have structural and molecular brain imaging focusing on hippocampal atrophy as a predictor of memory consolidation. We will also assess amyloid and tau in the medial temporal region as function of OSA severity and as a predictor of neurocognitive function. This aim will lay the groundwork for designing a robust clinical trial using neuroimaging outcomes.

Hypothesis 3: Impairment in memory consolidation is a function of hippocampal size in OSA patients at risk of AD.

Aim 4: We will perform a pilot randomized trial of oxygen vs. PAP therapy in OSA patients with preclinical AD.

Hypothesis 4: In preclinical AD with OSA, oxygen will be a viable therapeutic strategy to improve memory.

Conditions

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OSA Sleep Apnea Obstructive Sleep Apnea Alzheimer Disease

Keywords

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sleep OSA Sleep Apnea Obstructive Sleep Apnea Alzheimer Disease Sleep Disorder Alzheimer

Study Design

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Allocation Method

RANDOMIZED

Intervention Model

CROSSOVER

Primary Study Purpose

TREATMENT

Blinding Strategy

SINGLE

Participants
If subjects have been randomized to receive room air, subjects will have a nasal cannula with pressurized room air to avoid unblinding.

Study Groups

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Supplemental Oxygen during PSG

Subjects will be instrumented with a nasal cannula to receive 2L/min supplemental oxygen. The oxygen will be kept at a fixed rate, however, the participant will be titrated to receive a max of 4 liters per min to maintain sats \>90% based on oximetry readings.

Group Type ACTIVE_COMPARATOR

Supplemental Oxygen

Intervention Type OTHER

Subjects will be instrumented with a nasal cannula to receive 2L/min supplemental oxygen. The oxygen will be kept at a fixed rate, however, the participant will be titrated to receive a max of 4 liters per min to maintain sats \>90% based on oximetry readings.

Room Air during PSG

Subjects will be instrumented with a nasal cannula to receive 2L/min of pressurized room air. The room air will be kept at a fixed rate, however, the participant will be titrated to receive a max of 4 liters per min to maintain sats \>90% based on oximetry readings.

Group Type PLACEBO_COMPARATOR

Room Air

Intervention Type OTHER

Subjects will be instrumented with a nasal cannula to receive 2L/min pressurized room air. The room air will be kept at a fixed rate, however, the participant will be titrated to receive a max of 4 liters per min to maintain sats \>90% based on oximetry readings.

Supplemental Oxygen for 3 Months

Over a 12-week period, participants randomized to receive supplemental Oxygen for treatment of OSA will be contacted weekly to be asked about their adherence. Participants' adherence will also be monitored remotely through cloud-based monitoring.

Group Type EXPERIMENTAL

Supplemental Oxygen

Intervention Type OTHER

Subjects will be instrumented with a nasal cannula to receive 2L/min supplemental oxygen. The oxygen will be kept at a fixed rate, however, the participant will be titrated to receive a max of 4 liters per min to maintain sats \>90% based on oximetry readings.

PAP Therapy for 3 Months

Over a 12-week period, participants randomized to receive supplemental PAP therapy for treatment of OSA will be contacted weekly to be asked about their adherence. Participants' adherence will also be monitored remotely through cloud-based monitoring.

Group Type EXPERIMENTAL

Continuous Positive Airway Pressure Machine

Intervention Type DEVICE

Continuous positive airway pressure is a form of positive airway pressure ventilation in which a constant level of pressure greater than atmospheric pressure is continuously applied to the upper respiratory tract of a person.

Interventions

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Supplemental Oxygen

Subjects will be instrumented with a nasal cannula to receive 2L/min supplemental oxygen. The oxygen will be kept at a fixed rate, however, the participant will be titrated to receive a max of 4 liters per min to maintain sats \>90% based on oximetry readings.

Intervention Type OTHER

Continuous Positive Airway Pressure Machine

Continuous positive airway pressure is a form of positive airway pressure ventilation in which a constant level of pressure greater than atmospheric pressure is continuously applied to the upper respiratory tract of a person.

Intervention Type DEVICE

Room Air

Subjects will be instrumented with a nasal cannula to receive 2L/min pressurized room air. The room air will be kept at a fixed rate, however, the participant will be titrated to receive a max of 4 liters per min to maintain sats \>90% based on oximetry readings.

Intervention Type OTHER

Other Intervention Names

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Oxygen O2 CPAP PAP Placebo

Eligibility Criteria

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Inclusion Criteria

1. Age 65-85 years
2. Gender: Men or Women
3. MOCA \> 26
4. Independently living and able to drive
5. OSA (AHI ≥ 15/h) or no OSA
6. Subjects must consent to waiving their right to obtain their PHS score (since the score is not yet actionable and could lead to social stress and ethical dilemmas)

Exclusion Criteria

1. Currently smoking
2. History of COPD or asthma
3. Heart Failure Class III or IV, unstable cardiovascular disease, or uncontrolled hypertension
4. Neuromuscular Disease
5. Drowsy Driving (ESS \> 18/24)
6. Inability to complete study procedures, such as questionnaire that are only available/validated in English
7. Lack of decisional capacity to provide informed consent
8. Participants in whom magnetic resonance imaging Magnetic Resonance Imaging \[MRI\] is contraindicated including, but not limited to, those with a pacemaker, presence of metallic fragments near the eyes or spinal cord, or cochlear implant
9. Presence of a brain tumor or lobar stroke
10. Current drug or alcohol abuse/dependence
11. Prisoners
Minimum Eligible Age

65 Years

Maximum Eligible Age

85 Years

Eligible Sex

ALL

Accepts Healthy Volunteers

No

Sponsors

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University of California, San Diego

OTHER

Sponsor Role lead

Responsible Party

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Atul Malhotra

Professor, Medicine

Responsibility Role PRINCIPAL_INVESTIGATOR

Locations

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UCSD Sleep Research

La Jolla, California, United States

Site Status RECRUITING

Countries

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United States

Central Contacts

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Pam DeYoung

Role: CONTACT

Phone: 8582462154

Email: [email protected]

Pamela DeYoung

Role: CONTACT

Phone: 8582462154

Email: [email protected]

Facility Contacts

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Pam DeYoung, RPSGT

Role: primary

Pamela DeYoung, RPSGT

Role: backup

References

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Holloway BM, Harding CD, DeYoung P, Kwan CG, Avetisyan L, Lui KK, Ancoli-Israel S, Banks SJ, Djonlagic I, Malhotra A. Comorbid insomnia and sleep apnea (COMISA) is associated with worse verbal episodic memory in older women. J Clin Sleep Med. 2025 Sep 30. doi: 10.5664/jcsm.11902. Online ahead of print.

Reference Type DERIVED
PMID: 41025403 (View on PubMed)

Harding CD, Holloway BM, DeYoung PN, Kwan C, Djonlagic I, Ancoli-Israel S, Banks SJ, Malhotra A. Subjective daytime sleepiness, not sleep quality or hypoxia, predicts sleep-dependent memory consolidation in a cohort of older adults. J Clin Sleep Med. 2025 Jul 1;21(7):1217-1226. doi: 10.5664/jcsm.11648.

Reference Type DERIVED
PMID: 40135690 (View on PubMed)

Other Identifiers

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200228

Identifier Type: -

Identifier Source: org_study_id