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OpenTrials
Completed

NCT Number: NCT04575740

Phenotyping Mechanistic Pathways for Adverse Health Outcomes in Sleep Apnea

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").

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Key information

Conditions

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

Age range

21 year–80 year

Sex eligibility

All sexes

Study type

Interventional

Phase

Not applicable

Primary location

Brigham and Women's Hospital

Boston, Massachusetts, 02115, United States

Who can participate

Healthy volunteers accepted: No

Only the study team can determine whether someone qualifies for participation.

Inclusion criteria

  • Adults aged 21-80 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)

Treatment and study plan

PAP

Device

Positive airway pressure to treat sleep apnea

Primary outcomes

  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 outcomes

  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.

Sponsors and collaborators

Lead sponsor

Brigham and Women's Hospital

Other

Collaborators

  • National Heart, Lung, and Blood Institute (NHLBI)

Registry information

Important dates

Study start
2020
Primary completion
2025
Study completion
2025
First posted
Oct 5, 2020
Registry last updated
Dec 16, 2025

OpenTrials presents study information sourced from ClinicalTrials.gov. The official registry record should be consulted for the latest information.

View the official ClinicalTrials.gov record (opens in a new tab)

This listing is for discovery and informational purposes only. It is not medical advice, does not guarantee that a study is recruiting, and does not determine eligibility. Contact the study team and a qualified healthcare professional when considering participation.

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