Recruiting

OSA

Sponsor:

California Pacific Medical Center Research Institute

Code:

NCT05988385

Conditions

Obstructive Sleep Apnea

Cognitive Decline

Eligibility Criteria

Sex: All

Age: 55 - 70+

Healthy Volunteers: Not accepted

Interventions

Positive airway pressure

Oral appliance therapy

Positional therapy

Study Details

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

Study ID

NCT05988385

Start date

Aug 29, 2024

Status verified date

Aug, 2026

Completion date

May 31, 2028

Anticipated

Primary completion date

Jun 30, 2027

Anticipated

Eligibility Criteria

Eligibility Criteria

Sex: All

Age: 55 - 70+

Healthy Volunteers: Not accepted

Inclusion Criteria:

  • 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
  • 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

Exclusion Criteria:

  • Documented diagnosis of chronic insomnia, or sleep onset insomnia based on Insomnia Severity Index - an 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
  • Chronic regular use (> 2 nights per week) of sedatives/hypnotics 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. 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. 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 comorbid condition 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. Delirium in the last 12 months.
  • Near-miss or prior automobile accident "due to sleepiness" within the past 12 months.
  • Employed as a commercial driver during the study (for example, bus drivers, train engineers, airplane pilots).
  • Any use of neuroleptics, benzodiazepines, barbiturates, opiates or anti-amyloid therapies.
  • Use of other cognitive enhancing drugs will also be excluded if initiated in the last 3 months, or not on stable dose.
  • Consumption of >14 alcohol drinks per week, unless alcohol consumption can be reduced if initiated in the last 3 months.

Study Design

Enrollment

200 participants

Anticipated

Allocation

Randomized

Intervention Model

Parallel Assignment

Primary purpose

Treatment

Interventions and Outcome Measures

Arms

active comparator: 3-month OSA treatment

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).

other: Waitlist control group

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

Interventions

Positive airway pressure

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.

Oral appliance therapy

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.

Positional therapy

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.

Primary outcome measure

  • Change in overnight memory retention on the A-B verbal paired associates task [ Time Frame: 3 months ]
  • Change in overnight memory retention on the A-B verbal paired associates task [ Time Frame: 12 months ]
  • Change in overnight memory retention on the A-B verbal paired associates task [ Time Frame: 24 months ]
  • Change in Aβ42/ Aβ40 ratio [ Time Frame: 3 months ]
  • Change in Aβ42/ Aβ40 ratio [ Time Frame: 24 months ]
  • Change in Plasma P-tau181 [ Time Frame: 3 months ]
  • Change in Plasma P-tau181 [ Time Frame: 24 months ]
  • Change in P-tau217 [ Time Frame: 3 months ]
  • Change in P-tau217 [ Time Frame: 24 months ]
  • Change in Neurofibrilary light (NfL) [ Time Frame: 3 months ]
  • Change in Neurofibrilary light (NfL) [ Time Frame: 24 months ]
  • Preclinical Cognitive Composite Score [ Time Frame: 3 months ]
  • Preclinical Cognitive Composite Score [ Time Frame: 12 months ]
  • Preclinical Cognitive Composite Score [ Time Frame: 24 months ]

Central Contacts and Locations

Central contacts

Lisa Takemori

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

Katie L Stone, PhD

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

Locations

University of Arizona

Recruiting

Tucson, Arizona, United States, 85719

Principal Investigator:

Sairam Parsasarathy, MD

New York University

Recruiting

New York, New York, United States, 10016

Principal Investigator:

Acibiades Rodriguez, MD

Mount Sinai

Recruiting

New York, New York, United States, 10023

Principal Investigator:

Andrew Varga, MD

University of Pittsburgh

Recruiting

Pittsburgh, Pennsylvania, United States, 15213

Principal Investigator:

Sanjay Patel, MD

More Information

Sponsor

California Pacific Medical Center Research Institute

Last update posted

Aug 6, 2026

Last verified

Aug, 2026

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

Trial information was received from ClinicalTrials.gov and was last updated on 2026-09-10. This information was provided to ClinicalTrials.gov by California Pacific Medical Center Research Institute on 2026-08-06.