MCI:OSA: MCI: CPAP Treatment of OSA (Memories2)

Sponsor
University of Pennsylvania (Other)
Overall Status
Recruiting
CT.gov ID
NCT03113461
Collaborator
National Institute on Aging (NIA) (NIH)
460
4
3
92.5
115
1.2

Study Details

Study Description

Brief Summary

The purpose of this project is to determine whether obstructive sleep apnea (OSA) treatment with positive airway pressure therapy (CPAP) can delay the progression of cognitive impairment in patients with amnestic Mild Cognitive Impairment (MCI) as measured by cognitive testing, and brain magnetic resonance imaging (MRI) scans. Study participants will be assessed at baseline, six-month (cognitive tests only) and one-year follow-up.

Condition or Disease Intervention/Treatment Phase
  • Device: CPAP
N/A

Detailed Description

A growing number of research studies suggest that obstructive sleep apnea (OSA), characterized by episodic nocturnal collapse of the upper airway and reduction/cessation of breathing leading to significant nocturnal hypoxia, is associated with an increased risk of cognitive impairment. OSA is effectively treated with continuous positive airway pressure (CPAP), a pressurized nasal/face mask worn during sleep, but health care providers do not often prescribe it for Mild Cognitive Impairment (MCI) because there are no large, prospective research studies in this population confirming efficacy.

This multi-site study will have a sample size of n=460 divided into three groups followed for one year: 1) a CPAP adherent group (approximately n=200); 2) two control groups consisting of 2a) a CPAP non-adherent control group (approximately n=160) and 2b) a no apnea control group (n=100). This will allow us to confirm whether CPAP treatment, controlling for risk factors such as neuroimaging findings and OSA severity at baseline, predicts the primary outcome of cognitive function at 1-year follow-up. Study participants will also undergo an Amyloid PET scan, use wearable activity monitors and functional/structural MRI brain scans.

This research study will thus examine the one year effects of CPAP on cognitive function and elucidate physiological mechanisms for cognitive decline in aMCI and OSA.

Study Design

Study Type:
Interventional
Anticipated Enrollment :
460 participants
Allocation:
Non-Randomized
Intervention Model:
Parallel Assignment
Intervention Model Description:
CPAP interventionCPAP intervention
Masking:
Single (Outcomes Assessor)
Primary Purpose:
Treatment
Official Title:
Changing the Trajectory of Mild Cognitive Impairment With CPAP Treatment of Obstructive Sleep Apnea
Actual Study Start Date :
Oct 15, 2017
Anticipated Primary Completion Date :
Dec 31, 2022
Anticipated Study Completion Date :
Jul 1, 2025

Arms and Interventions

Arm Intervention/Treatment
Experimental: CPAP adherent

Study participants in this arm are using the CPAP intervention consistently

Device: CPAP
non-invasive positive airway pressure applied using an oronasal mask
Other Names:
  • continuous positive airway pressure therapy
  • Active Comparator: CPAP non-adherent

    Study participants in this arm are not using the CPAP intervention consistently

    Device: CPAP
    non-invasive positive airway pressure applied using an oronasal mask
    Other Names:
  • continuous positive airway pressure therapy
  • No Intervention: No OSA

    Study participants who do not have OSA

    Outcome Measures

    Primary Outcome Measures

    1. Digit Symbol-Coding test [one-year follow-up]

      incorporates both elements of memory and processing speed and correlates with executive functioning

    Secondary Outcome Measures

    1. Clinical Dementia Rating Scale [one-year follow-up]

      Assessment of global cognition

    Eligibility Criteria

    Criteria

    Ages Eligible for Study:
    55 Years to 85 Years
    Sexes Eligible for Study:
    All
    Accepts Healthy Volunteers:
    No
    Inclusion Criteria:
    1. age 55-85 years;

    2. moderate to severe OSA as defined by an AHI ≥ 15 events/hr, or no apnea defined by an AHI<5 events/hr using American Academy of Sleep Medicine (AASM) diagnostic methodology as determined on a diagnostic polysomnography;

    3. Scoring education adjusted scores 28-35 (inclusive) on optional Telephone Interview for Cognitive Status Modified (pre-screen);

    4. Scoring 0-0.5 on the Clinical Dementia Rating Scale (CDR);

    5. Scoring 23-30 on the Mini Mental State Examination (MMSE) (exceptions may be made for participants with <8 years of education as determined by the clinical research team);

    6. Memory impairment approximately 1.0-1.5 standard deviations below normal (adjusted for age and education) determined by scores on the Logical Memory II a test from the Wechsler memory scale;

    7. permitted medications (antidepressants, etc.) stable for at least 4 weeks (12 weeks for cholinesterase inhibitors/memantine) as per ADNI3 criteria;

    8. Non-depressed: Scoring < 6 on the Geriatric Depression Scale;

    9. study partner, defined as an informant/caregiver who will be able to answer questions about the study participant, and meets one of the following criteria: (a) lives with the participant; (b) spends at least 3 times per week in-person contact with the participant; (c) spends at least 3 times per week in phone contact with the participant; or (d) spends at least 10 hours per week in any combination of phone or in person contact;

    10. adequate visual and auditory acuity to allow testing;

    11. Post-menopause or surgically sterile;

    12. testability - willing and able to complete baseline, 6-month, and 1-year outcome measures, and willing to send in the CPAP Smartcard for adherence;

    13. completed at least 6 grades of education; and

    14. fluent in English or Spanish.

    Exclusion Criteria:
    1. any significant neurologic disease other than aMCI, such as Parkinson's Disease, Huntington's disease, normal pressure hydrocephalus, progressive supranuclear palsy, multiple sclerosis, head trauma followed by permanent neurologic deficits or known congenital brain structure abnormalities; within the past 6 months brain tumor, or seizure disorder, or subdural hematoma, or post-stroke (based on Modified Hachinski Ischemic Score);

    2. Optional: MRI exclusions - presence of pacemakers, aneurysm clips, artificial heart valves, ear implants, metal fragments or foreign objects in the eyes, skin, or body; however, the participant has the option of participating in the study without having an MRI;

    3. psychiatric disorders, including uncontrolled major depression, newly diagnosed or exacerbation in past 6 months of bipolar disorder as described in the DSM-IV, psychotic features, agitation or behavioral problems within the past 6 months that could lead to difficulty complying with the protocol, or history of schizophrenia (DSM-IV criteria);

    4. history of alcohol abuse or dependence within the past 6 months (DSM-IV criteria);

    5. any current significant systemic illness or unstable medical condition that could lead to difficulty in complying with the protocol (such as unstable cardiovascular disease); current use of supplemental oxygen or hypoxemia indicated by documented daytime oxyhemoglobin saturation <90% on room air, uncontrolled thyroid disease (to be included must be on stable dose of thyroid medication for >6 months), uncontrolled cirrhosis, cancer diagnosis within the past 6 months (exceptions may be made at the PI's discretion depending on cancer severity and the treatment required), clinically significant laboratory abnormalities such as reported untreated folate, B12, or TSH disease, or resident of a skilled nursing facility;

    6. participation in clinical studies involving neuropsychological measures being conducted more than twice a year;

    7. received and was adherent to CPAP or bi-level pressure for OSA within the past 6 months;

    Contacts and Locations

    Locations

    Site City State Country Postal Code
    1 Washington University in St. Louis Saint Louis Missouri United States 63130-4862
    2 University of Pennsylvania Philadelphia Pennsylvania United States 19104
    3 University of Texas at Austin Austin Texas United States 78701
    4 University of Virginia Charlottesville Virginia United States 22903

    Sponsors and Collaborators

    • University of Pennsylvania
    • National Institute on Aging (NIA)

    Investigators

    • Principal Investigator: Nalaka Gooneratne, MD, MSc, Associate Professor
    • Principal Investigator: Kathy Richards, PhD, Professor
    • Principal Investigator: David Wolk, MD, Associate Professor

    Study Documents (Full-Text)

    None provided.

    More Information

    Publications

    None provided.
    Responsible Party:
    University of Pennsylvania
    ClinicalTrials.gov Identifier:
    NCT03113461
    Other Study ID Numbers:
    • PD10057866
    • R01AG054435
    First Posted:
    Apr 13, 2017
    Last Update Posted:
    May 6, 2021
    Last Verified:
    May 1, 2021
    Individual Participant Data (IPD) Sharing Statement:
    Undecided
    Plan to Share IPD:
    Undecided
    Studies a U.S. FDA-regulated Drug Product:
    No
    Studies a U.S. FDA-regulated Device Product:
    Yes
    Product Manufactured in and Exported from the U.S.:
    Yes
    Keywords provided by University of Pennsylvania
    Additional relevant MeSH terms:

    Study Results

    No Results Posted as of May 6, 2021