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The Brain Changes in Sleep Apnea Study

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ClinicalTrials.gov Identifier: NCT03410095
Recruitment Status : Not yet recruiting
First Posted : January 25, 2018
Last Update Posted : February 21, 2018
Sponsor:
Collaborator:
University of Edinburgh
Information provided by (Responsible Party):
Dr. Andrew Lim, Sunnybrook Health Sciences Centre

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 7 days 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.

Condition or disease Intervention/treatment
Sleep Sleep Apnea Sleep Apnea Syndromes Diagnostic Test: Brain MRI, cognitive testing, bloodwork

Detailed Description:
Between January 2018 and February 2020, the Brain Changes in Sleep Apnea Study will recruit 80 adults with newly diagnosed severe sleep apnea attending the sleep clinics at Sunnybrook Health Sciences Centre (n=40) or the University of Edinburgh (n=40). Participants will undergo home-based assessment with 3 wearable devices (24 hours of ambulatory blood pressure monitoring, 7 days of actigraphy to assess sleep duration and fragmentation, and 1 night of finger-probe peripheral arterial tonometry and oximetry to assess cardiorespiratory physiology including sleep apnea), completion of a sleep and health questionnaire, 24-hour collection of urine for assessing sympathetic nervous system activity, blood banking for endothelial biomarkers, cognitive evaluation, pulse wave velocity test, and an MRI of the brain, at 2 time points: 1) after initial polysomnographic diagnosis of sleep apnea but before the initiation of CPAP, and 2) after 4 months of CPAP treatment.

Study Type : Observational [Patient Registry]
Estimated Enrollment : 80 participants
Observational Model: Cohort
Time Perspective: Prospective
Target Follow-Up Duration: 4 Months
Official Title: The Brain Changes in Sleep Apnea Study
Estimated Study Start Date : March 15, 2018
Estimated Primary Completion Date : February 15, 2020
Estimated Study Completion Date : February 15, 2020

Resource links provided by the National Library of Medicine

MedlinePlus related topics: Sleep Apnea

Group/Cohort Intervention/treatment
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

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.





Primary Outcome Measures :
  1. Change from baseline in perivascular space volume [ Time Frame: Baseline and 4 months ]
    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.

  2. Change from baseline in DTI fractional anisotropy on voxel-wise basis [ Time Frame: Baseline and 4 months ]
    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.

  3. Change from baseline in a summary measure of arterial pulsatility [ Time Frame: Baseline and 4 months ]
    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).

  4. Change from baseline in perivascular lactate measured by MR spectroscopy [ Time Frame: Baseline and 4 months ]
    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).

  5. Change from baseline in cerebrovascular reactivity on a voxel-wise basis [ Time Frame: Baseline and 4 months ]
    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.


Secondary Outcome Measures :
  1. Change from baseline in 24-hour blood pressure [ Time Frame: Baseline and 4 months ]
    We will quantify the main effect of CPAP treatment on 24-hour blood pressure (as measured by the ambulatory blood pressure monitor).

  2. Change from baseline in sleep duration and fragmentation [ Time Frame: Baseline and 4 months ]
    We will quantify the main effect of CPAP treatment on sleep duration and fragmentation (as measured by the GENEActiv).

  3. Change from baseline in severity of sleep apnea, % deep NREM sleep, and hypoxemia [ Time Frame: Baseline and 4 months ]
    We will quantify the main effect of CPAP treatment on severity of sleep apnea, % deep NREM sleep, and hypoxemia (as measured by the WatchPAT).

  4. Change from baseline in serum markers of metabolic, inflammatory, cardiovascular, and endothelial function [ Time Frame: Baseline and 4 months ]
    We will quantify the main effect of CPAP treatment on serum markers of metabolic, inflammatory, cardiovascular, and endothelial function (as measured by blood tests).

  5. Change from baseline in urinary measures of sympathetic nervous system [ Time Frame: Baseline and 4 months ]
    We will quantify the main effect of CPAP treatment on urinary measures of sympathetic nervous system (as measured with urine test).

  6. Change from baseline in cognitive performance [ Time Frame: Baseline and 4 months ]
    We will quantify the main effect of CPAP treatment on cognitive performance (as measured by our computerized battery, which includes the MoCA, BNA-R, and BrainScreen).


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 (25-30 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.


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Ages Eligible for Study:   18 Years and older   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
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).
Criteria

Inclusion Criteria:

  • Newly diagnosed sleep apnea not on CPAP or any other treatment for sleep apnea;
  • Apnea hypopnea index >=15 on diagnostic polysomnogram;
  • O2 saturation in sleep <90% for >30 minutes;
  • Subjectively sleepy;
  • Planning on starting CPAP for sleep apnea.

Exclusion Criteria:

  • 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.

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT03410095


Contacts
Contact: Giselle Kraus, MSc 416-480-5143 sleepapneabrain@sunnybrook.ca

Sponsors and Collaborators
Dr. Andrew Lim
University of Edinburgh
Investigators
Principal Investigator: Andrew Lim, MD, FRCPC Sunnybrook Health Sciences Centre

Publications:
Radloff, L.S. (1977). The CED-D scale: A self-report depression scale for research in the general population. Applied Psychological Measurement, 1, 385-401

Responsible Party: Dr. Andrew Lim, Scientist, staff neurologist, Sunnybrook Health Sciences Centre
ClinicalTrials.gov Identifier: NCT03410095     History of Changes
Other Study ID Numbers: SleepApneaStudy
First Posted: January 25, 2018    Key Record Dates
Last Update Posted: February 21, 2018
Last Verified: February 2018
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: No

Studies a U.S. FDA-regulated Drug Product: No
Studies a U.S. FDA-regulated Device Product: No
Product Manufactured in and Exported from the U.S.: No

Additional relevant MeSH terms:
Apnea
Sleep Apnea Syndromes
Respiration Disorders
Respiratory Tract Diseases
Signs and Symptoms, Respiratory
Signs and Symptoms
Sleep Disorders, Intrinsic
Dyssomnias
Sleep Wake Disorders
Nervous System Diseases