CPAP Randomized Controlled Trial

Not Applicable

Not yet recruiting

• Conditions: Obstructive Sleep Apnea (OSA); Mild Cognitive Impairment (MCI); Cognitive Decline Prevention in Pre-frail Older Adults

• Registration Number: NCT06773416
• Lead Sponsor: Sunnybrook Health Sciences Centre

Brief Summary

The overall goal of this randomized controlled trial is to test the hypothesis that in older adults with mild cognitive impairment (MCI) and previously untreated obstructive sleep apnea (OSA), 4 months of web-based sleep education and continuous positive airway pressure (CPAP) will improve cognitive function more than web-based sleep education alone. Secondarily, this trial will test the hypothesis that 8 months of CPAP will improve cognitive function more than 4 months of CPAP. Moreover, treating OSA with CPAP can improve cognitive function and reduce Alzheimer's disease-related brain changes in older adults with MCI.

This study will compare an Early CPAP Group who will receive CPAP and sleep education simultaneously for 8 months upon enrollment to a Later CPAP Group who will first receive sleep education for 4 months followed by CPAP and sleep education for the next 4 months to test if early treatment is more beneficial.

Participants will:

1. Complete web-based sleep education modules through the Brain Health Pro (BHP) platform

2. Undergo CPAP therapy, including in-person mask fitting and regular monitoring alongside a study sleep technologist

At 0 months, 4 months, and 8 months, participants will participate in cognitive assessments, provide blood samples, use wearable devices to measure sleep patterns and physiology, and complete a 1-hr MRI (0 months and 4 months only).

Detailed Description

This clinical study is a single-blinded, randomized controlled trial of 206 adults designed to evaluate the impact of CPAP therapy on cognitive function and Alzheimer's disease-related pathology in older adults with MCI and untreated OSA. Participants will be randomized into two groups: the first group receiving CPAP treatment alongside sleep education upon enrollment for 8 months (Early CPAP group) and the other beginning CPAP treatment after 4 months of sleep education (Later CPAP group).

1. Early CPAP Group: Participants randomized to this group will start BHP-sleep and CPAP simultaneously and continue both for 8 months. BHP-sleep consists of the sleep modules of the Canadian Consortium on Neurodegeneration in Aging's (CCNA) online Brain Health PRO platform covering sleep physiology, healthy sleep habits, and information about sleep disorders like sleep apnea. Participants will receive a study-provided auto-titrating CPAP device, with settings set by one of the study sleep medicine physicians according to current clinical practice parameters. Participants will undergo an in-person mask fitting, and then will be supported by a sleep technologist with extensive clinical experience with CPAP.

2. Later CPAP Group: Participants randomized to this group will start BHP-sleep without CPAP for first 4 months, followed by BHP-sleep and CPAP simultaneously for remaining 4 months of participation.

Participants in both groups will register at baseline for the web-based sleep education through the Brain Health Pro (BHP) platform; a 45-week, multidomain, web-based formal educational program designed to increase dementia literacy, foster engagement, and convey best available evidence for lifestyle changes that can mitigate dementia risk. This protocol will utilize the sleep modules of the BHP platform covering sleep physiology, healthy sleep habits, and information about sleep disorders like sleep apnea.

This trial will assess cognitive function primarily using the Symbol Digit Modalities Test (SDMT); a test of speeded executive function that is predictive of clinically significant improvement in patients with MCI, alongside additional cognitive measures that supplement the primary outcome of this study will be: attention and executive function (Trail Making Test A \& B), working memory (Digit Span and Letter-Number Sequencing), verbal learning and memory (Hopkins Verbal Learning Test), and severity of cognitive impairment (Alzheimer's Disease Assessment Scale - Cognitive Subscale; ADAS-Cog-13).

This trial will also quantify brain perivascular spaces (PVS) volume and structural changes, plasma glial fibrillary acidic protein (GFAP) and plasma pTau-181.

This trial will also aim to identify features of sleep physiology that mediate the impact of CPAP on cognitive function.

Study Timeline

• Status Verified: 2024-12
• Study First Submitted: 2025-01-08
• Study First Submitted QC: 2025-01-08
• Last Update Submitted: 2025-01-08
• Study First Posted: 2025-01-14
• Last Update Posted: 2025-01-14
• Study Start: 2025-02
• Primary Completion: 2027-09
• Study Completion: 2028-01

Recruitment & Eligibility

• Status: NOT_YET_RECRUITING
• Sex: All
• Target Recruitment: 206

Inclusion Criteria

• Informed consent obtained and signed
• Age >55
• MCI: Participants will undergo a video-based screening, including a clinical interview, Logical Memory II, MoCA, and Lawton-Brody Instrumental Activities of Daily Living Scale Score. A participant will be considered to have MCI if they have: 1) MoCA score of 13-24 and Logical Memory II Score ≤ 8 (&=16 years of education), ≤ 4 (8-15 years of education) or ≤ 2 (0-7 years of education) and Lawton-Brody IADL Score >14/23 and do not meet DSM IV criteria for dementia and have a change in self-perceived cognition from previous
• Moderate-severe OSA: Participants who screen positive for MCI will be mailed an at-home sleep apnea testing device. Participants with ODI≥5 will undergo in-lab polysomnography (PSG) for confirmation and characterization of sleep apnea. A participant will be considered to have moderate-severe OSA if they have on PSG: AHI>15, and ODI>10, and central apneas<10% of all apneas, and periodic limb movement index <15.

Exclusion Criteria

• drowsiness-related driving accidents or near misses in the past 12 months
• drives as their primary occupation
• unable to complete cognitive evaluation in English
• unable to participate in video-based cognitive assessment
• not a resident of Ontario
• contraindications to MRI
• contraindications to CPAP or unwilling to start CPAP
• no available study partner to support CPAP
• previously treated for sleep apnea
• clinically significant insomnia (ISI > 15), restless legs syndrome, or shift work
• taking disease modifying agents for MCI

Study & Design

• Study Type: INTERVENTIONAL
• Study Design: PARALLEL

Primary Outcome Measures

Name	Time	Method
Change in Symbol Digit Modalities Test (SDMT)	From Week 0 to Week 32	The SDMT is a test of speeded executive function that is predictive of clinically significant improvement in patients with MCI with a well-defined minimal clinically significant change and that is responsive to CPAP in observational studies. Additional cognitive measures that supplement the primary outcome of this study will be: attention and executive function (Trail Making Test A \& B), working memory (Digit Span and Letter-Number Sequencing), verbal learning and memory (Hopkins Verbal Learning Test), and severity of cognitive impairment (Alzheimer's Disease Assessment Scale - Cognitive Subscale; ADAS-Cog-13).

Secondary Outcome Measures

Name	Time	Method
Vascular Risk Factors and AD-biomarkers	From Week 0 to Week 32	Quantification of plasma pTau181 (AD pathology) using ptau-181 V2.1 Advantage Assay and GFAP (astrocyte activation) using the GFAP discovery assay.; Blood levels of various fats, sugars and proteins (such as cholesterol or glucose) will be assessed.; Sleep physiology will be assessed using wearable sensors: at-home sleep apnea testing apparatus (for oximetry metrics including AHI, ODI, mean SpO2, hypoxia burden, and time with O2\<92%), EEG headband (sleep staging, including % slow wave sleep, % REM sleep, total EEG sleep time, and NREM slow wave power), and wrist-worn accelerometry (for total sleep time and sleep fragmentation).
MRI	From Week 0 to Week 16	Participants will undergo MRI using the Canadian Dementia Imaging protocol consisting of a 3D T1, interleaved 3mm PD/T2, 3D FLAIR, T2\*, DTI, and resting state BOLD. Perivascular spaces and white matter hyperintensities will be quantified with the SynthSegCSVD algorithm developed and validated in our laboratory, a robust neural network based tool.

Trial Locations

Locations (1)

Sunnybrook Health Sciences Centre; 🇨🇦 Toronto, Ontario, Canada