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

Alzheimer Disease Clinical Trial

Official title:

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

Clinical Trial Details — Status: Recruiting

Administrative data

• NCT number: NCT05094271
• Other study ID #: 200228
• Status: Recruiting
• Phase: Phase 1
• Start date: June 30, 2021
• Est. completion date: March 20, 2025

Study information

• Verified date: December 2023
• Source: University of California, San Diego
• Contact: Pam DeYoung
• Phone: 8582462154
• Email: sleepresearch[@]health.ucsd.edu
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

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.

Description:

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.

Recruitment information / eligibility

• Status: Recruiting
• Enrollment: 260
• Est. completion date: March 20, 2025
• Est. primary completion date: March 2, 2025
• Accepts healthy volunteers: No
• Gender: All
• Age group: 65 Years to 85 Years

Eligibility

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

Related Conditions & MeSH terms

• Alzheimer Disease
• Apnea
• Obstructive Sleep Apnea
• OSA
• Sleep Apnea
• Sleep Apnea Syndromes
• Sleep Apnea, Obstructive

Intervention

Other:
• 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.

Device:
• 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.

Other:
• 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.

Locations

Country	Name	City	State
United States	UCSD Sleep Research	La Jolla	California

Sponsors (1)

Lead Sponsor	Collaborator
University of California, San Diego

Country where clinical trial is conducted

United States, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Loop Gain (LG)	A method used to measure respiratory stability of the negative feedback chemoreflex control system using a specialized Positive Airway Pressure machine called a pCrit. The overall loop gain of the ventilatory system reflects the ratio of the ventilatory response to the disturbance that elicited the response (LG = ventilatory response/ventilatory disturbance). The higher the loop gain, the potentially more unstable the respiratory control system becomes.	8 hours
Primary	Apnea Hypopnea Index	The number of times a person stops breathing and periods of shallow breathing with a marked decrease in blood oxygen concentration every hour on average. A score lower than five indicates normal sleep (no sleep apnea), 5-15 indicates mild sleep apnea, 15-30 indicates moderate sleep apnea, and a score greater than 30 indicates severe sleep apnea.	8 hours
Primary	Neuroimaging	MRI and PET Scans. This study will examine pre-clinical AD with OSA patients using brain imaging (structural MRI and amyloid/tau PET). MRI will be conducted to provide a structural image suitable for coregistering the PET image and observing white matter integrity. The scan should take 35 minutes. These will be MPRAGE images collected using the standard ADNI protocol at the in-house 3T MRI scanner at the UCSD Altman Clinical and Translational Research Institute (ACTRI). The PET scan should take 70-90 minutes.	2 hours
Secondary	Epworth Sleepiness Scale (ESS)	A self-administered questionnaire with 8 questions. Respondents are asked to rate, on a 4-point scale (0-3), their usual chances of dozing off or falling asleep while engaged in eight different activities. The ESS score (the sum of 8 item scores, 0-3) can range from 0 to 24. The higher the ESS score, the higher that person's average sleep propensity in daily life.	12 weeks
Secondary	Pittsburg Sleep Quality Index (PSQI)	A 19-item, self-rated questionnaire designed to measure sleep quality and disturbance over the past month. The sleep component scores are summed to yield a total score ranging from 0 to 21 with the higher total score (referred to as global score) indicating worse sleep quality.	12 weeks
Secondary	Insomnia Severity Index (ISI)	A 7-item self-report form to assess insomnia severity. Total score categories: 0-7 = No clinically significant insomnia, 8-14 = Subthreshold insomnia, 15-21 = Clinical insomnia (moderate severity), 22-28 = Clinical insomnia (severe).	12 weeks