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Phenotyping Mechanistic Pathways for Adverse Health Outcomes in Sleep Apnea

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ClinicalTrials.gov Identifier: NCT04575740
Recruitment Status : Recruiting
First Posted : October 5, 2020
Last Update Posted : October 14, 2020
Sponsor:
Collaborator:
National Heart, Lung, and Blood Institute (NHLBI)
Information provided by (Responsible Party):
Ali Azarbarzin, Brigham and Women's Hospital

Brief Summary:

Obstructive sleep apnea (OSA) is a highly prevalent disorder with adverse neurocognitive and cardio-metabolic outcomes. Continuous positive airway pressure (CPAP) is the gold standard therapeutic option to treat airway obstructions during sleep and thus, prevent its adverse cardiovascular and neurocognitive outcomes. Previous clinical trials, however, have largely failed to show a consistent impact of CPAP on these health outcomes.

One of the main limitations of these trials may be the inadequate characterization of OSA and its acute physiological consequences. By characterizing OSA based on the "apnea-hypopnea index (AHI)", there is a potential risk of negative results.

In this trial, the investigators intend to tackle this issue, by better characterization of OSA-related physiological consequences during sleep using physiologically driven metrics to capture the burden of OSA-related hypoxemia ("hypoxic burden"), autonomic response ("heart rate burden"), and sleep fragmentation ("arousal burden").


Condition or disease Intervention/treatment Phase
Sleep Apnea Device: PAP Not Applicable

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Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 158 participants
Allocation: N/A
Intervention Model: Single Group Assignment
Masking: None (Open Label)
Primary Purpose: Diagnostic
Official Title: Phenotyping Mechanistic Pathways for Adverse Health Outcomes in Sleep Apnea
Actual Study Start Date : September 10, 2020
Estimated Primary Completion Date : June 30, 2024
Estimated Study Completion Date : June 30, 2024

Resource links provided by the National Library of Medicine

MedlinePlus related topics: Sleep Apnea

Arm Intervention/treatment
Experimental: Positive Airway Pressure Device
All participants will receive PAP therapy
Device: PAP
Positive airway pressure to treat sleep apnea




Primary Outcome Measures :
  1. Change from baseline flow-mediated vasodilation at 12 weeks [ Time Frame: 12 weeks ]
    Flow mediated vasodilation is studied using high resolution ultrasound of the artery.

  2. Change from baseline 24-hour mean systolic blood pressure at 12 weeks [ Time Frame: 12 weeks ]
    Mean systolic blood pressure over a 24-hour period is measured using an ambulatory blood pressure monitor.

  3. Change from baseline Epworth Sleepiness Scale (ESS) at 12 weeks [ Time Frame: 12 weeks ]
    Self-reported sleepiness measured using the Epworth Sleepiness Scale (units on a scale). Values range from 0-24; higher values indicate greater sleepiness.


Secondary Outcome Measures :
  1. Change from baseline F2-Isoprostane/Creatinine Ratio at 12 weeks [ Time Frame: 12 weeks ]
    F2-Isoprostane/Creatinine Ratio, a measure of oxidative stress, is calculated from urine sample.

  2. Change from baseline Albumin/Creatinine Ratio at 12 weeks [ Time Frame: 12 weeks ]
    Urinary Albumin/Creatinine Ratio is calculated from urine samples.

  3. Change from baseline Albumin without Creatinine at 12 weeks [ Time Frame: 12 weeks ]
    Urinary Albumin is calculated from urine samples.

  4. Change from baseline Oxidized low-density lipoprotein (LDL) at 12 weeks [ Time Frame: 12 weeks ]
    Oxidized low-density lipoprotein measurements are calculated through fasting phlebotomy.

  5. Change from baseline N-terminal pro b-type natriuretic peptide (NT-proBNP) at 12 weeks [ Time Frame: 12 weeks ]
    N-terminal pro b-type natriuretic peptide (NT-proBNP) measurements are calculated through fasting phlebotomy.

  6. Change from baseline Hemoglobin A1c (HbA1c) at 12 weeks [ Time Frame: 12 weeks ]
    Hemoglobin A1c (HbA1c) measurements are calculated through fasting phlebotomy.

  7. Change from baseline Plasminogen Activator Inhibitor-1 at 12 weeks [ Time Frame: 12 weeks ]
    Plasminogen activator inhibitor type 1 (PAI-1) measurements are calculated through fasting phlebotomy.

  8. Change from baseline Fibrinogen Antigen at 12 weeks [ Time Frame: 12 weeks ]
    Fibrinogen Antigen measurements are calculated through fasting phlebotomy. High values indicate inflammation and increased risk of atherosclerosis.

  9. Change from baseline Glucose at 12 weeks [ Time Frame: 12 weeks ]
    Blood glucose measurements are calculated through fasting phlebotomy

  10. Change from baseline high sensitivity C-Reactive Protein (hs-CRP) at 12 weeks [ Time Frame: 12 weeks ]
    C-reactive protein measurements are calculated from blood samples collected through fasting phlebotomy.

  11. Change from baseline Interleukin-6 (IL-6) at 12 weeks [ Time Frame: 12 weeks ]
    IL-6 is calculated from blood samples collected through fasting phlebotomy

  12. Change from baseline Creatinine at 12 weeks [ Time Frame: 12 weeks ]
    Creatinine is calculated from blood samples collected through fasting phlebotomy

  13. Change from baseline Cystanin C with eGFR at 12 weeks [ Time Frame: 12 weeks ]
    Cystanin C with eGFR is calculated from blood samples collected through fasting phlebotomy

  14. Change from baseline lipid panel at 12 weeks [ Time Frame: 12 weeks ]
    Lipid panel measurements are calculated from blood samples collected through fasting phlebotomy.

  15. Change from baseline 24-hour mean diastolic blood pressure at 12 weeks [ Time Frame: 12 weeks ]
    Mean diastolic blood pressure over a 24-hour period is measured using an ambulatory blood pressure monitor.

  16. Change from baseline 24-hour mean blood pressure at 12 weeks [ Time Frame: 12 weeks ]
    Mean arterial blood pressure over a 24-hour period is measured using an ambulatory blood pressure monitor.

  17. Change from baseline nocturnal mean systolic blood pressure at 12 weeks [ Time Frame: 12 weeks ]
    Mean systolic blood pressure during sleep is measured using an ambulatory blood pressure monitor.

  18. Change from baseline nocturnal mean diastolic blood pressure at 12 weeks [ Time Frame: 12 weeks ]
    Mean diastolic blood pressure during sleep is measured using an ambulatory blood pressure monitor.

  19. Change from baseline nocturnal mean blood pressure at 12 weeks [ Time Frame: 12 weeks ]
    Mean arterial blood pressure during sleep is measured using an ambulatory blood pressure monitor.

  20. Change from baseline Psychomotor Vigilance Task reaction time at 12 weeks [ Time Frame: 12 weeks ]
    3-minute Psychomotor Vigilance Tasks will be done to quantify the speed with which subjects respond to a visual stimulus.

  21. Change from baseline Psychomotor Vigilance Task lapses per test at 12 weeks [ Time Frame: 12 weeks ]
    3-minute Psychomotor Vigilance Tasks will be done to quantify the speed with which subjects respond to a visual stimulus.

  22. Change from baseline Functional Outcome of Sleep Questionnaire (FOSQ) at 12 weeks [ Time Frame: 12 weeks ]
    This test will be used to assess the impact of excessive sleepiness on functional outcomes relevant to daily behaviors and sleep-related quality of life.



Information from the National Library of Medicine

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Ages Eligible for Study:   21 Years to 70 Years   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
Criteria

Inclusion criteria:

  • Adults aged 21-70 years.
  • Participants with a previous diagnosis of moderate to severe obstructive sleep will be eligible to enroll and attend the baseline study. Patients with a total apnea-hypopnea index greater than 15 events/hr on the baseline study will be eligible for further participation.

Exclusion criteria:

  • Current treatment for obstructive sleep apnea (including CPAP, oral appliances, supplemental oxygen). Patients must be untreated prior to the baseline visit.
  • Use of medications that might depress respiration (including opioids, barbiturates, benzodiazepines, and Z drugs, including zolpidem, zopiclone, eszopiclone, and zaleplon).
  • Active use of non-prescription opioids (e.g., cocaine, methamphetamine)
  • Uncontrolled medical problem or major organ system disease, which, in the opinion of the investigators (PI and Co-Is), would interfere with the evaluation of the subject (e.g., uncontrolled hypertension, unstable coronary heart disease, etc.).
  • History of congestive heart failure, renal insufficiency, systemic neurological condition that could affect respiration.
  • Sleep disordered breathing or respiratory disorders other than obstructive sleep apnea:

    • central sleep apnea (>50% of respiratory events scored as central),
    • chronic hypoventilation/hypoxemia (awake SaO2 < 92% by oximetry) due to chronic obstructive pulmonary disease or other respiratory conditions.
  • Other sleep disorders: periodic limb movements (periodic limb movement arousal index > 10/hr), narcolepsy, or parasomnias.
  • Patients unable or unwilling to use CPAP.
  • Insomnia or insufficient sleep (self-reported inability to sleep >6 hrs night).
  • Pregnancy (women)

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): NCT04575740


Contacts
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Contact: Lauren Hess 617-732-8976 lhess1@bwh.harvard.edu
Contact: Kiley E Blodgett 617-732-8976 keblodgett@bwh.harvard.edu

Locations
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United States, Massachusetts
Brigham and Women's Hospital Recruiting
Boston, Massachusetts, United States, 02115
Contact: Lauren Hess    617-732-8976    lhess1@bwh.harvard.edu   
Contact: Kiley Blodgett       keblodgett@bwh.harvard.edu   
Sponsors and Collaborators
Brigham and Women's Hospital
National Heart, Lung, and Blood Institute (NHLBI)
Investigators
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Principal Investigator: Ali Azarbarzin, PhD Brigham and Women's Hospital
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Responsible Party: Ali Azarbarzin, Associate Scientist, Brigham and Women's Hospital
ClinicalTrials.gov Identifier: NCT04575740    
Other Study ID Numbers: PhenOSA
1R01HL153874 ( U.S. NIH Grant/Contract )
First Posted: October 5, 2020    Key Record Dates
Last Update Posted: October 14, 2020
Last Verified: October 2020
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: Yes
Supporting Materials: Study Protocol

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Studies a U.S. FDA-regulated Drug Product: No
Studies a U.S. FDA-regulated Device Product: Yes
Keywords provided by Ali Azarbarzin, Brigham and Women's Hospital:
Sleep apnea
Hypoxic burden
Arousal intensity
Post-event tachycardia
Positive airway pressure
Apnea hypopnea index
Additional relevant MeSH terms:
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Apnea
Sleep Apnea Syndromes
Respiration Disorders
Respiratory Tract Diseases
Signs and Symptoms, Respiratory
Sleep Disorders, Intrinsic
Dyssomnias
Sleep Wake Disorders
Nervous System Diseases