The Effects of Successful OSA Treatment on Memory and AD Biomarkers in Older Adults Study

NCT05988385 | Recruiting DMC FDA Device

• 1 other identifier: AG080609
• Study Type: interventional
• Target: 200
• Locations: 1 country
• Sites: 4

Brief Summary

The Effects of Successful OSA TreatmENT on Memory and AD BIomarkers in Older AduLts (ESSENTIAL) study is a 5-year, multicenter randomized open-label trial that will screen 400 cognitively normal older adults recruited from well-established sleep clinics at 4 academic medical centers, with newly diagnosed moderate-severe OSA. An expected 200 OSA patients will be then randomized to one of two groups: i) a 3-month OSA treatment by any combination of PAP, OAT, and positional therapy that results in an "effective" AHI4%\< 10/hour and AHI3A\<20/hour (see below); ii) a waitlist control group to receive treatment at the conclusion of the 3-month intervention period. Both groups will continue follow-up for 24 months on stable therapy to determine if sustained improvements in sleep are associated with improvement in cognitive function and AD biomarkers.

Conditions

Obstructive Sleep Apnea; Cognitive Decline

Keywords

Obstructive Sleep Apnea; OSA; Cognitive decline; Alzheimer Disease; AD; AD biomarkers; Positive Airway Pressure; PAP; CPAP; Oral appliance therapy; OAT; Positional therapy; Sleep-dependent memory

Outcome Measures

Primary Outcomes (14)

• Change in overnight memory retention on the A-B verbal paired associates task

  Mean change in percent correct memory

  3 months

• Change in overnight memory retention on the A-B verbal paired associates task

  Mean change in percent correct memory

  12 months

• Change in overnight memory retention on the A-B verbal paired associates task

  Mean change in percent correct memory

  24 months

• Change in Aβ42/ Aβ40 ratio

  Mean change in the Aβ42/ Aβ40 ratio in picograms per millimeter (pg/ml)

  3 months

• Change in Aβ42/ Aβ40 ratio

  Mean change in the Aβ42/ Aβ40 ratio in picograms per millimeter (pg/ml)

  24 months

• Change in Plasma P-tau181

  Mean change in p-tau181 levels in the plasma in picograms per millimeter (pg/ml)

  3 months

• Change in Plasma P-tau181

  Mean change in p-tau181 levels in the plasma in picograms per millimeter (pg/ml)

  24 months

• Change in P-tau217

  Mean change in p-tau217 levels in the plasma in picograms per millimeter (pg/ml)

  3 months

• Change in P-tau217

  Mean change in p-tau217 levels in the plasma in picograms per millimeter (pg/ml)

  24 months

• Change in Neurofibrilary light (NfL)

  Mean change in NfL levels in the plasma in picograms per millimeter (pg/ml)

  3 months

• Change in Neurofibrilary light (NfL)

  Mean change in NfL levels in the plasma in picograms per millimeter (pg/ml)

  24 months

• Preclinical Cognitive Composite Score

  Mean change in Preclinical Cognitive Composite Score.

  3 months

• Preclinical Cognitive Composite Score

  Mean change in Preclinical Cognitive Composite Score.

  12 months

• Preclinical Cognitive Composite Score

  Mean change in Preclinical Cognitive Composite Score.

  24 months

Secondary Outcomes (12)

• Change in Task-switching Accuracy

  3 months

• Change in Task-switching Accuracy

  12 months

• Change in Task-switching Accuracy

  24 months

• Change in Task-switching Reaction Time

  3 months

• Change in Task-switching Reaction Time

  12 months

Other Outcomes (12)

• Cognitive Impairment Severity

  Baseline

• Cognitive Impairment Severity

  24 months

• Clinical Dementia Rating (CDR) Scale (0-3)

  Baseline

Study Arms (2)

3-month OSA treatment

ACTIVE COMPARATOR

A 3-month OSA treatment by any combination of PAP, OAT, and positional therapy that results in an "effective" AHI3a\<15 (rapid multi-modal treatment RMMT).

Device: Positive airway pressure; Device: Oral appliance therapy; Device: Positional therapy

Waitlist control group

OTHER

A waitlist control group to receive treatment at the conclusion of the 3-month intervention period.

Device: Positive airway pressure; Device: Oral appliance therapy; Device: Positional therapy

Interventions

Positive airway pressure DEVICE

Positive airway pressure (PAP) therapy is a sleep apnea treatment that uses a stream of compressed air to support the airway during sleep. With PAP therapy, a mask is worn during sleep and a portable machine gently blows pressurized room air from into your upper airway through a tube connected to the mask. This positive airflow helps keep the airway open, preventing the collapse that occurs during apnea, thus allowing normal breathing.

Also known as: CPAP

3-month OSA treatment; Waitlist control group

Oral appliance therapy DEVICE

Oral appliance therapy involves the use of a dental appliance or oral mandibular advancement device that prevents the tongue from blocking the throat and/or advances the lower jaw forward. These devices help keep the airway open during sleep.

Also known as: OAT, ProSomnus, Somnomed

3-month OSA treatment; Waitlist control group

Positional therapy DEVICE

A NightShift Sleep Positioner (Advanced Brain Monitoring) is a neck vibration device, FDA approved to treat positional sleep apnea. The device detects patient supine position and delivers a small vibratory signal to the back of the neck to prompt position change.

Also known as: NightShift Sleep Positioner

3-month OSA treatment; Waitlist control group

Eligibility Criteria

• Age: 55 Years - 85 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Cognitively normal (TiCS ≥29)
• Age 55-85 years
• Moderate - severe OSA defined as AHI4 ≥20 events/hour or AHI3A\>40/hr using a hypopnea criterion of a 4% oxygen desaturation (AHI4) or 3% oxygen desaturation and/or EEG arousal (AHI3A), or equivalent based on in-home testing - Testing must have been completed in past 12 months or confirmed by repeat test (EHR)
• Not currently on therapy for OSA and has not received treatment for OSA for at least 6months
• Able and willing to be treated for OSA (Treatment group)
• Fluency in English or Spanish

You may not qualify if:

• Documented diagnosis of chronic insomnia, or sleep onset insomnia based on Insomnia Severity Index - a answer of severe or very severe in the screening form
• Documented diagnosis of circadian rhythm disorder
• Any current use of supplemental oxygen
• Other sleep-related breathing disorders (central sleep apnea, etc) based on AASM criteria
• Current shift work involving night shift (regular work between 12am and 6am or night shift) within the past 6 mo
• Anticipated scheduled bariatric surgery within the next 3 months
• Chronic regular (\> 2 nights per week) of cannabis for sleep
• Diagnosis of uncontrolled psychiatric disease in the last six months , and/or history of schizophrenia or bipolar disorder. Controlled conditions will include major depressive disorder, panic disorder, generalized anxiety disorder, OCD, substance use disorders, and alcohol abuse/dependence. (medical record/EHR). Personality disorders and neurodevelopmental disorders (e.g. autism, ADHD) are allowed if cognition is within normal limits.
• Taking methylphenidate for ADHD. Unless on stable dose which will be reviewed by the PI to determine.
• Taking GLP-1 agonist semaglutide (Ozempic, Wegovy, Rybelsus), or tirzepatide (Mounjaro, Zepbound), or similar for weightloss, and planning to lose an additional 20lbs or more at the time of enrollment. (Screening form/Electronic Medical Record) PI Discretion for determination of why they are taking the drug based on conversation with subject and medical chart, will be documented in form of Note-to-file in the subject's records
• Presence of other critical comorbid conditions that would lead to inability to complete the study protocol (including follow-up for 2 years), or that would affect cognition (e.g. clinically relevant endocrine or hematological conditions).
• Does not have a regular sleeping environment (i.e., sleeps in a different setting \> 2 nights per week).
• Currently pregnant or planning to become pregnant.
• Prior diagnosis of a Central nervous system (CNS) disease, such as multiple sclerosis, stroke, Parkinson's disease, Alzheimer's disease, epilepsy, a loss of consciousness \> 24 hours, or traumatic brain injury as identified by the Cumulative Illness Rating Scale for Geriatrics (CIRS). Participants who are diagnosed with MCI or Alzheimer's disease based on neuropsychological testing will be excluded. (CLINIC RECORDS/EHR). Delirium in the last 12 months.
• Near-miss or prior automobile accident "due to sleepiness" within the past 12 months.

Sponsors & Collaborators

• California Pacific Medical Center Research Institute: lead
• Icahn School of Medicine at Mount Sinai: collaborator
• New York University: collaborator
• University of Arizona: collaborator
• University of Pittsburgh: collaborator
• National Institute on Aging (NIA): collaborator

Study Sites (4)

University of Arizona

Tucson, Arizona, 85719, United States

RECRUITING

New York University

New York, New York, 10016, United States

RECRUITING

Mount Sinai

New York, New York, 10023, United States

RECRUITING

University of Pittsburgh

Pittsburgh, Pennsylvania, 15213, United States

RECRUITING

MeSH Terms

Conditions

Sleep Apnea, Obstructive; Cognitive Dysfunction; Alzheimer Disease

Condition Hierarchy (Ancestors)

Sleep Apnea Syndromes; Apnea; Respiration Disorders; Respiratory Tract Diseases; Sleep Disorders, Intrinsic; Dyssomnias; Sleep Wake Disorders; Nervous System Diseases; Cognition Disorders; Neurocognitive Disorders; Mental Disorders; Dementia; Brain Diseases; Central Nervous System Diseases; Tauopathies; Neurodegenerative Diseases

Study Officials

• Katie L Stone, PhD

  California Pacific Medical Center Research Institute

  PRINCIPAL INVESTIGATOR

• Ricardo Osorio, MD

  New York University

  PRINCIPAL INVESTIGATOR

• Andrew Varga, MD

  Icahn School of Medicine at Mount Sinai

  PRINCIPAL INVESTIGATOR

Central Study Contacts

Lisa Takemori

CONTACT

415-633-6229; lisa.takemori@ucsf.edu

Katie L Stone, PhD

CONTACT

415-476-6128; katie.stone@ucsf.edu

Study Design

• Study Type: interventional
• Phase: not applicable
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Model Details: Approximately 250 total patients (\~63 per site) will be enrolled. In the 3-month wait-list control randomized trial, 200 patients will be randomized to one of two groups: i) a 3-month OSA treatment by any combination of PAP, OAT, and positional therapy that results in an "effective" AHI3a\<15 (rapid multi-modal treatment RMMT); ii) a waitlist control group to receive treatment at the conclusion of the 3-month intervention period. The remaining 50, plus an additional \~50 (n\~100 total) participants who declined treatment and were not interested in being randomized for the 3-month trial, or who have tried but failed treatment in the past, will serve as the "control" group for the 24-month follow-up period.

Study Record Dates

• First Submitted: May 22, 2023
• First Posted: August 14, 2023
• Study Start: April 22, 2024
• Primary Completion (Estimated): June 30, 2027
• Study Completion (Estimated): May 31, 2028
• Last Updated: November 10, 2025

Record last verified: 2025-06

Data Sharing

• IPD Sharing: Will share
• Shared Documents: STUDY PROTOCOL, ICF
• Time Frame: Research data that documents, supports, and validates research findings will be available after the main findings from the final research data set are accepted for publication. We anticipate data will be available starting in January 2029 and will be available on an NIH-sponsored platform for as long as the agency supports it.
• Access Criteria: Data and associated documentation available to users only under a data-sharing agreement that provides for: (1) a commitment to using the data only for research purposes and not to identify any individual participant; (2) a commitment to securing the data using appropriate computer technology; and (3) a commitment to destroying or returning the data after analyses are completed.

Locations

US (4)