CPAP Randomized Controlled Trial

Sunnybrook Health Sciences Centre

Status: Not yet enrolling

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

Treatments: Combination Product: CPAP Therapy Combined with Web-Based Sleep Education for Cognitive and Sleep Health; Combination Product: Delayed CPAP Therapy Combined with Web-Based Sleep Education for Cognitive and Sleep Health

Study type: Interventional

Funder types: Other

Identifiers

NCT06773416

BH-10967 (Other Grant/Funding Number)

CTO 5040

Details and patient eligibility

About

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).

Full 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.

Enrollment: 206 estimated patients

Sex: All

Ages: 55+ years old

Volunteers: No Healthy Volunteers

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

Trial design

Primary purpose: Treatment

Allocation: Randomized

Interventional model: Parallel Assignment

Masking: Single Blind

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206 participants in 2 patient groups

Group 1 (Early CPAP group)

Experimental group

Description:

Participant will receive a study-provided CPAP device at their baseline visit, with settings set by one of the study sleep medicine physicians according to current clinical practice parameters. Participant will undergo an in-person mask fitting and then will be supported by a study sleep technologist with extensive clinical experience with CPAP who will contact the participant by telephone or video call at set intervals. Masks, tubing, chin straps, and other equipment necessary to optimize CPAP adherence will be provided by the study. Adherence will be monitored through downloads from the CPAP device. Participant will be asked to use CPAP nightly during their participation in this study. Participant will simultaneously participate in web-based sleep education through the Brain Health Pro (BHP) platform; a formal educational program designed to increase dementia literacy, foster engagement, and convey best available evidence for lifestyle changes that can mitigate dementia risk.

Treatment:

Combination Product: CPAP Therapy Combined with Web-Based Sleep Education for Cognitive and Sleep Health

Group 2 (Later CPAP group)

Active Comparator group

Description:

Participant will receive the web-based sleep educational intervention first for 4 months. Participant will then receive a study-supplied CPAP device with settings set by one of the study sleep medicine physicians according to current clinical practice parameters. Participant will undergo an in-person mask fitting and will be supported by a study sleep technologist with extensive clinical experience with CPAP who will contact the participant by telephone or video call at set intervals. Equipment necessary to optimize CPAP adherence will be provided. Adherence will be monitored through downloads from the CPAP device. Participant will be asked to use CPAP nightly throughout their participation. Participant will simultaneously participate in web-based sleep education through the Brain Health Pro platform; a formal educational program designed to increase dementia literacy, foster engagement and convey best available evidence for lifestyle changes that can mitigate dementia risk.

Treatment:

Combination Product: Delayed CPAP Therapy Combined with Web-Based Sleep Education for Cognitive and Sleep Health