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

• ClinicalTrials.gov Identifier: NCT03113461
• Recruitment Status: Active, not recruiting
• First Posted: April 13, 2017
• Last Update Posted: April 12, 2023
• Sponsor: University of Pennsylvania
• Collaborator: National Institute on Aging (NIA)
• Information provided by (Responsible Party): University of Pennsylvania

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
Mild Cognitive Impairment; Sleep Apnea, Obstructive	Device: CPAP	Not Applicable

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 (Clinical Trial)
• Actual Enrollment: 327 participants
• Allocation: Non-Randomized
• Intervention Model: Parallel Assignment
• Intervention Model Description: CPAP 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: January 19, 2018
• Actual Primary Completion Date: January 31, 2023
• Estimated Study Completion Date: July 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 Name: 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 Name: 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 [ Time Frame: 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 [ Time Frame: one-year follow-up ]
   Assessment of global cognition

Eligibility Criteria

• Ages Eligible for Study: 55 Years to 85 Years (Adult, Older Adult)
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: No

Criteria

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

United States, Missouri

Washington University in St. Louis

Saint Louis, Missouri, United States, 63130-4862

United States, Pennsylvania

University of Pennsylvania

Philadelphia, Pennsylvania, United States, 19104

United States, Texas

University of Texas at Austin

Austin, Texas, United States, 78701

United States, Virginia

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

More Information

• Responsible Party: University of Pennsylvania
• ClinicalTrials.gov Identifier: NCT03113461
• Other Study ID Numbers: PD10057866; R01AG054435 ( U.S. NIH Grant/Contract )
• First Posted: April 13, 2017
• Last Update Posted: April 12, 2023
• Last Verified: April 2023

Individual Participant Data (IPD) Sharing Statement:

• Plan to Share IPD: Undecided
• Plan Description: Pending

• 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:

cognitive impairment; sleep apnea; positive airway pressure therapy

Additional relevant MeSH terms:

Apnea; Sleep Apnea Syndromes; Sleep Apnea, Obstructive; Cognitive Dysfunction; Respiration Disorders; Respiratory Tract Diseases; Signs and Symptoms, Respiratory; Sleep Disorders, Intrinsic; Dyssomnias; Sleep Wake Disorders; Nervous System Diseases; Cognition Disorders; Neurocognitive Disorders; Mental Disorders