The Brain Changes in Sleep Apnea Study

NCT03410095 | Unknown

• 1 other identifier: SleepApneaStudy
• Study Type: observational
• Target: 80
• Locations: 1 country
• Sites: 1

Brief Summary

Sleep is critical to human health, but insufficient and disrupted sleep caused by sleep apnea are common and have a major impact on brain health. However, there is still much that is not known about how sleep apnea damages the brain and what can be done to fix this. The Brain Changes in Sleep Apnea Study will look at the brain health of people with severe sleep apnea both before and after 4 months of treatment with a CPAP machine. Pre- and post-CPAP treatment, 80 participants with severe sleep apnea will undergo cognitive testing, blood and urine tests, a pulse wave velocity test, and an MRI. Also pre- and post-CPAP treatment, participants will wear a blood pressure monitor for 24 hours, wear an accelerometer watch for 8 nights to track the duration and quality of their sleep, and wear a device for 1 night of sleep to assess their breathing and blood oxygen levels. It is expected that there will be improvements in participants' brain health after 4 months of CPAP treatment.

Conditions

Sleep; Sleep Apnea; Sleep Apnea Syndromes

Outcome Measures

Primary Outcomes (5)

• Change from baseline in perivascular space volume

  We will use repeated measures linear mixed effect models to estimate the main effect of CPAP (i.e. compare pre- and post-CPAP measurements) on perivascular space volume.

  Baseline and 4 months

• Change from baseline in DTI fractional anisotropy on voxel-wise basis

  We will use repeated measures linear mixed effect models to estimate the main effect of CPAP (i.e. compare pre- and post-CPAP measurements) on DTI fractional anisotropy on voxel-wise basis.

  Baseline and 4 months

• Change from baseline in a summary measure of arterial pulsatility

  We will use repeated measures linear mixed effect models to estimate the main effect of CPAP (i.e. compare pre- and post-CPAP measurements) on arterial pulsatility (as measured by the pulse wave velocity test).

  Baseline and 4 months

• Change from baseline in perivascular lactate measured by MR spectroscopy

  We will use repeated measures linear mixed effect models to estimate the main effect of CPAP (i.e. compare pre- and post-CPAP measurements) on perivascular lactate (as measured by MR spectroscopy).

  Baseline and 4 months

• Change from baseline in cerebrovascular reactivity on a voxel-wise basis

  We will use repeated measures linear mixed effect models to estimate the main effect of CPAP (i.e. compare pre- and post-CPAP measurements) on cerebrovascular reactivity on a voxel-wise basis.

  Baseline and 4 months

Secondary Outcomes (6)

• Change from baseline in 24-hour blood pressure

  Baseline and 4 months

• Change from baseline in sleep duration and fragmentation

  Baseline and 4 months

• Change from baseline in severity of sleep apnea, % deep NREM sleep, and hypoxemia

  Baseline and 4 months

• Change from baseline in serum markers of metabolic, inflammatory, cardiovascular, and endothelial function

  Baseline and 4 months

• Change from baseline in urinary measures of sympathetic nervous system

  Baseline and 4 months

Study Arms (1)

Sleep apnea patients

80 patients recently diagnosed with severe sleep apnea will participate in the Brain Changes in Sleep Apnea Study.

Diagnostic Test: Brain MRI, cognitive testing, bloodwork

Interventions

Brain MRI, cognitive testing, bloodwork DIAGNOSTIC_TEST

Participants will undergo 3-Tesla MRI. Scan time will be about 1 hour and 15 minutes per subject per session at the Sunnybrook site. The protocol is designed to image SVD burden by quantifying PVS and WMH volumes, and image various physiological estimates on the brain. Participants will undergo the following cognitive tests: Behavioural Neurology Assessment-R (BNA-R), Montreal Cognitive Assessment (MOCA), Center for Epidemiologic Studies Depression Scale (CES-D), and BrainScreen. Blood samples will be assayed for inflammatory and endothelial function. Classical vascular risk factors will also be assessed. Once data collection is complete, DNA will be extracted from the frozen PBMC fraction and will be genotyped for APOE genotype and a panel of other single nucleotide polymorphisms known to be associated with cognition and cerebrovascular disease.

Sleep apnea patients

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)
• Sampling Method: Non-Probability Sample

Study Population

80 adults with newly diagnosed severe sleep apnea will be recruited from the sleep clinics at Sunnybrook Health Sciences Centre (n=40) or the University of Edinburgh (n=40).

You may qualify if:

• Newly diagnosed sleep apnea not on CPAP or any other treatment for sleep apnea;
• Apnea hypopnea index \>=15 on diagnostic polysomnogram;
• Oxygen desaturation index \>=10 or O2 saturation in sleep \<90% for \>15 minutes on diagnostic polysomnogram;
• Subjectively sleepy;
• Planning on starting CPAP for sleep apnea.

You may not qualify if:

• Known history of stroke, transient ischemic attack, or other CNS disease;
• Unable to safely undergo MRI;
• Use of alpha-blocking agents;
• Persistent non-sinus arrhythmia;
• Severe pulmonary or cardiac diseases including COPD and CHF;
• Waking spO2\<90%;
• History of panic disorder.

Sponsors & Collaborators

• Dr. Andrew Lim: lead
• University of Edinburgh: collaborator

Study Sites (1)

Sunnybrook Health Sciences Centre

Toronto, Ontario, M4N3M5, Canada

RECRUITING

Related Publications (34)

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  BACKGROUND

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  PMID: 41021868 DERIVED

Biospecimen

Retention: SAMPLES WITH DNA

Phlebotomy will be performed following an overnight fast, and samples will be banked for assessment of cytokines and endothelial biomarkers. Blood samples (45-50 ml) will be collected in plasma vacutainer tubes. Plasma will be separated and preserved in a freezer. The peripheral blood mononuclear cell (PBMC) fraction will also be kept in a freezer for genetic evaluation. All samples will be de-identified and preserved at -80oC and assayed together in a batch after the collection of the last sample (in 2020). Samples will be assayed for inflammatory and endothelial function by ELISA. Classical vascular risk factors will also be assessed.

MeSH Terms

Conditions

Sleep Apnea Syndromes

Condition Hierarchy (Ancestors)

Apnea; Respiration Disorders; Respiratory Tract Diseases; Sleep Disorders, Intrinsic; Dyssomnias; Sleep Wake Disorders; Nervous System Diseases

Study Officials

• Andrew Lim, MD, FRCPC

  Sunnybrook Health Sciences Centre

  PRINCIPAL INVESTIGATOR

Central Study Contacts

Andrew Centen, MSc

CONTACT

416-480-5143; sleepapneabrain@sunnybrook.ca

Study Design

• Study Type: observational
• Observational Model: COHORT
• Time Perspective: PROSPECTIVE
• Target Duration: 4 Months
• Sponsor Type: OTHER
• Responsible Party: SPONSOR INVESTIGATOR
• PI Title: Scientist, staff neurologist

Study Record Dates

• First Submitted: December 19, 2017
• First Posted: January 25, 2018
• Study Start: December 12, 2018
• Primary Completion: February 15, 2022
• Study Completion: June 15, 2022
• Last Updated: March 22, 2021

Record last verified: 2021-03

Data Sharing

• IPD Sharing: Will not share

Locations

CA (1)