NCT05988385 · California Pacific Medical Center Research Institute
The Effects of Successful OSA Treatment on Memory and AD Biomarkers in Older Adults Study
(ESSENTIAL)
What this study is about
The Effects of Successful OSA TreatmENT on Memory and AD BIomarkers in Older AduLts (ESSENTIAL) study is a 5-year, conducted at multiple hospitals randomly assigned where both patients and doctors know the treatment given 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.
View original scientific description
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.
Interventions
DEVICE
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.
DEVICE
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.
DEVICE
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 measures
Change in overnight memory retention on the A-B verbal paired associates task
Time frame: 3 months
Mean change in percent correct memory
Change in overnight memory retention on the A-B verbal paired associates task
Time frame: 12 months
Mean change in percent correct memory
Change in overnight memory retention on the A-B verbal paired associates task
Time frame: 24 months
Mean change in percent correct memory
Change in Aβ42/ Aβ40 ratio
Time frame: 3 months
Mean change in the Aβ42/ Aβ40 ratio in picograms per millimeter (pg/ml)
Change in Aβ42/ Aβ40 ratio
Time frame: 24 months
Mean change in the Aβ42/ Aβ40 ratio in picograms per millimeter (pg/ml)
Change in Plasma P-tau181
Time frame: 3 months
Mean change in p-tau181 levels in the plasma in picograms per millimeter (pg/ml)
Change in Plasma P-tau181
Time frame: 24 months
Mean change in p-tau181 levels in the plasma in picograms per millimeter (pg/ml)
Change in P-tau217
Time frame: 3 months
Mean change in p-tau217 levels in the plasma in picograms per millimeter (pg/ml)
Change in P-tau217
Time frame: 24 months
Mean change in p-tau217 levels in the plasma in picograms per millimeter (pg/ml)
Change in Neurofibrilary light (NfL)
Time frame: 3 months
Mean change in NfL levels in the plasma in picograms per millimeter (pg/ml)
Change in Neurofibrilary light (NfL)
Time frame: 24 months
Mean change in NfL levels in the plasma in picograms per millimeter (pg/ml)
Preclinical Cognitive Composite Score
Time frame: 3 months
Mean change in Preclinical Cognitive Composite Score.
Preclinical Cognitive Composite Score
Time frame: 12 months
Mean change in Preclinical Cognitive Composite Score.
Preclinical Cognitive Composite Score
Time frame: 24 months
Mean change in Preclinical Cognitive Composite Score.
Who can participate
This study lists these criteria on ClinicalTrials.gov. A study coordinator reviews eligibility during screening — this page does not determine whether you qualify.
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 (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
Exclusion criteria
- 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.
- 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
Where
- Tucson, Arizona
- New York, New York
- Pittsburgh, Pennsylvania
Collaborators
Icahn School of Medicine at Mount Sinai, New York University, University of Arizona, University of Pittsburgh, National Institute on Aging (NIA)
Related conditions & keywords
Frequently asked questions
What is a clinical trial?
A clinical trial is a research study that tests new medical treatments, drugs, devices, or procedures to determine their safety and effectiveness. Trials are carefully designed and monitored to protect participants while advancing medical knowledge.
Is it safe to participate?
Clinical trials follow strict safety guidelines and ethical standards. Trials must be reviewed and approved, and participants are closely monitored by medical professionals throughout the study. You can withdraw at any time if you choose.
Will I be compensated?
Many clinical trials offer compensation for your time, travel expenses, and inconvenience. The specific compensation varies by study and will be discussed during the screening process. All study-related medical care is typically provided at no cost to participants.
Will I receive a placebo instead of treatment?
When effective treatment exists, participants typically receive either the standard treatment plus the study intervention, or the standard treatment plus placebo. You would not be denied effective care. Placebos are primarily used when no proven treatment is available, or in addition to standard care. Your trial consent form will clearly explain what treatments you may receive.
Can I leave a trial if I change my mind?
Absolutely. Participation in clinical trials is completely voluntary. You have the right to withdraw from the study at any time, for any reason, without penalty or loss of benefits to which you are otherwise entitled.
How long does a clinical trial last?
Trial duration varies widely depending on the study design and purpose. Some trials last just a few weeks, while others may continue for months or years. The study coordinator will provide specific timeline information during your screening call.
Data: ClinicalTrials.gov · synced Nov 10, 2025 · Source of record for eligibility and locations