CPAP Randomized Controlled Trial

Official title

Treating Sleep Apnea to Improve Cognitive Function, Alzheimer's Disease Pathology, and Astrocyte Activation in Older Adults With Cognitive Impairment: A Multi-Centre Randomized Controlled Trial

Overview

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.

Interventions

• Combination product CPAP Therapy Combined with Web-Based Sleep Education for Cognitive and Sleep Health
  Participants in Group 1 will receive CPAP therapy immediately upon enrollment alongside web-based sleep education through the Brain Health Pro (BHP) platform. The CPAP intervention includes a study-provided auto-titrating device, in-person mask fitting, and ongoing support from a study sleep technologist. Adherence will be monitored via remote data uploads. The BHP platform is a 45-week web-based formal educational program program designed to increase dementia literacy, foster engagement, and co
• Combination product Delayed CPAP Therapy Combined with Web-Based Sleep Education for Cognitive and Sleep Health
  Participants in Group 2 will begin with 4 months of BHP web-based sleep education before adding CPAP therapy for the remaining 4 months. CPAP setup and support are identical to the Early CPAP group. Participants in Group 2 will experience procedure similar to current clinical practices.

Primary outcome measures

• Change in Symbol Digit Modalities Test (SDMT) [Time frame: From Week 0 to Week 32]

Secondary outcome measures (2)

• Vascular Risk Factors and AD-biomarkers [Time frame: From Week 0 to Week 32]
• MRI [Time frame: From Week 0 to Week 16]

Eligibility criteria

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

Criteria are shown verbatim from the registry (in English). Final eligibility is always assessed by the study center.

Healthy volunteers: No

Study design

Allocation

Randomized

Model

Parallel assignment

Masking

Single blind

Primary purpose

Treatment

Study locations

Canada · 1 center

• Sunnybrook Health Sciences Centre — Toronto

Publications

• Hedner J, White DP, Malhotra A, Herscovici S, Pittman SD, Zou D, Grote L, Pillar G. Sleep staging based on autonomic signals: a multi-center validation study. J Clin Sleep Med. 2011 Jun 15;7(3):301-6. doi: 10.5664/JCSM.1078. PMID 21677901
• Onder NS, Akpinar ME, Yigit O, Gor AP. Watch peripheral arterial tonometry in the diagnosis of obstructive sleep apnea: influence of aging. Laryngoscope. 2012 Jun;122(6):1409-14. doi: 10.1002/lary.23233. Epub 2012 Apr 20. PMID 22522750
• Crowley KE, Rajaratnam SM, Shea SA, Epstein LJ, Czeisler CA, Lockley SW; Harvard Work Hours, Health and Safety Group. Evaluation of a single-channel nasal pressure device to assess obstructive sleep apnea risk in laboratory and home environments. J Clin Sleep Med. 2013 Feb 1;9(2):109-16. doi: 10.5664/jcsm.2400. PMID 23372462
• Lawton MP, Brody EM. Assessment of older people: self-maintaining and instrumental activities of daily living. Gerontologist. 1969 Autumn;9(3):179-86. No abstract available. PMID 5349366
• Benedict RHB, Schretlen D, Groninger L, &amp; Brandt J (1998). Hopkins Verbal Learning Test - Revised: Normative Data and Analysis of Inter-Form and Test-Retest Reliability. The Clincal Neuropsychologist, 12(1), 43-55.
• Wechsler D. The Psychological Corporation; 1997. WMS-III Administration and Scoring Manual.
• Esther Strauss, O. S. (1998). Trail Making Tests. New York, Oxford University Press.
• Yesavage JA, Brink TL, Rose TL, Lum O, Huang V, Adey M, Leirer VO. Development and validation of a geriatric depression screening scale: a preliminary report. J Psychiatr Res. 1982-1983;17(1):37-49. doi: 10.1016/0022-3956(82)90033-4. PMID 7183759

Identifiers

NCT: NCT06773416 · CTO 5040 · BH-10967

Primary sources (government registries)

• ClinicalTrials.gov (US NIH)

View this study on ClinicalTrials.gov ↗