Phenotyping Mechanistic Pathways for Adverse Health Outcomes in Sleep Apnea

NCT04575740 | Completed FDA Device

• 2 other identifiers: PhenOSA1R01HL153874
• Study Type: interventional
• Target: 209
• Locations: 1 country
• Sites: 1

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").

Conditions

Sleep Apnea

Keywords

Sleep apnea; Hypoxic burden; Arousal intensity; Post-event tachycardia; Positive airway pressure; Apnea hypopnea index

Outcome Measures

Primary Outcomes (3)

• Change from baseline flow-mediated vasodilation at 12 weeks

  Flow mediated vasodilation is studied using high resolution ultrasound of the artery.

  12 weeks

• Change from baseline 24-hour mean systolic blood pressure at 12 weeks

  Mean systolic blood pressure over a 24-hour period is measured using an ambulatory blood pressure monitor.

  12 weeks

• Change from baseline Epworth Sleepiness Scale (ESS) at 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.

  12 weeks

Secondary Outcomes (22)

• Change from baseline F2-Isoprostane/Creatinine Ratio at 12 weeks

  12 weeks

• Change from baseline Albumin/Creatinine Ratio at 12 weeks

  12 weeks

• Change from baseline Albumin without Creatinine at 12 weeks

  12 weeks

• Change from baseline Oxidized low-density lipoprotein (LDL) at 12 weeks

  12 weeks

• Change from baseline N-terminal pro b-type natriuretic peptide (NT-proBNP) at 12 weeks

  12 weeks

Study Arms (1)

Positive Airway Pressure Device

EXPERIMENTAL

All participants will receive PAP therapy

Device: PAP

Interventions

PAP DEVICE

Positive airway pressure to treat sleep apnea

Positive Airway Pressure Device

Eligibility Criteria

• Age: 21 Years - 80 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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.

You may not qualify if:

• 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)

Sponsors & Collaborators

• Brigham and Women's Hospital: lead
• National Heart, Lung, and Blood Institute (NHLBI): collaborator

Study Sites (1)

Brigham and Women's Hospital

Boston, Massachusetts, 02115, United States

Location

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

• Ali Azarbarzin, PhD

  Brigham and Women's Hospital

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: not applicable
• Allocation: NA
• Masking: NONE
• Purpose: DIAGNOSTIC
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Associate Scientist

Study Record Dates

• First Submitted: September 16, 2020
• First Posted: October 5, 2020
• Study Start: September 10, 2020
• Primary Completion: June 30, 2025
• Study Completion: September 30, 2025
• Last Updated: December 16, 2025

Record last verified: 2024-08

Data Sharing

• IPD Sharing: Will share
• Shared Documents: STUDY PROTOCOL

Locations

US (1)