Assessment of Continuous Positive Airway Pressure Therapy in OSA and ILD

NCT03901534 | Terminated Results DMC FDA Device

• 2 other identifiers: AAAR69021R01HL137234-01
• Study Type: interventional
• Target: 2,021
• Locations: 1 country
• Sites: 2

Brief Summary

The purpose of this study is to evaluate whether biomarkers of lung epithelial and endothelial injury are associated with obstructive sleep apnea (OSA) and interstitial lung disease (ILD).

Conditions

Interstitial Lung Disease; Obstructive Sleep Apnea

Keywords

Interstitial Lung Disease (ILD); Obstructive Sleep Apnea (OSA); CPAP

Outcome Measures

Primary Outcomes (10)

• Surfactant Protein D (SP-D) [Aim 1]

  SP-D is a marker of alveolar epithelial cell injury. This Outcome is specific to Aim 1 and will only be measured on participants in the Aim 1 phase of the study.

  1 day

• E-selectin [Aim 1]

  This Outcome is specific to Aim 1 and will only be measured on participants in the Aim 1 phase of the study.

  1 day

• Angiopoietin-2 [Aim 1]

  This Outcome is specific to Aim 1 and will only be measured on participants in the Aim 1 phase of the study.

  1 day

• Vascular Endothelial Growth Factor-A (VEGF-A) [Aim 1]

  This Outcome is specific to Aim 1 and will only be measured on participants in the Aim 1 phase of the study.

  1 day

• Angiopoietin-interacting Soluble Tie-2 (sTie2) [Aim 1]

  This Outcome is specific to Aim 1 and will only be measured on participants in the Aim 1 phase of the study.

  1 day

• Change in Serum Matrix Metalloproteinase-7 (MMP-7) Following CPAP [Aim 2]

  The differences between-arms in the longitudinal changes of MMP-7 will be measured. For the purpose of this analysis, all individuals receiving active CPAP in the experimental arm will be compared to all individuals receiving sham CPAP device in the control arm. This Outcome is specific to Aim 2 and will only be measured on participants in the Aim 2 phase of the study.

  Baseline and post-CPAP follow-up, up to 24 Weeks

• Change in Serum Surfactant Protein-D (SP-D) Following CPAP [Aim 2]

  The between-arm difference in the longitudinal changes of SP-D will be measured. For the purpose of this analysis, all individuals receiving active CPAP in the experimental arm will be compared to all individuals receiving sham CPAP device in the control arm. This Outcome is specific to Aim 2 and will only be measured on participants in the Aim 2 phase of the study.

  Baseline and post-CPAP follow-up, up to 24 Weeks

• Change in Serum Angiopoietin-2 (Ang-2) Following CPAP [Aim 2]

  The between-arm difference in the longitudinal changes of Ang-2 will be measured. For the purpose of this analysis, all individuals receiving active CPAP in the experimental arm will be compared to all individuals receiving sham CPAP device in the control arm. This Outcome is specific to Aim 2 and will only be measured on participants in the Aim 2 phase of the study.

  Baseline and post-CPAP follow-up, up to 24 Weeks

• Change in Serum Osteopontin Following CPAP [Aim 2]

  The differences between-arms in the longitudinal changes of Osteopontin will be measured. For the purpose of this analysis, all individuals receiving active CPAP in the experimental arm will be compared to all individuals receiving sham CPAP device in the control arm. This Outcome is specific to Aim 2 and will only be measured on participants in the Aim 2 phase of the study.

  Baseline and post-CPAP follow-up, up to 24 Weeks

• Serum Angiopoietin-2 (Ang-2, ng/mL) [Aim 3a]

  Participants will be treated with CPAP for 4 weeks. Serum Ang-2 levels will be measured at baseline and after CPAP therapy. This Outcome is specific to Aim 3a and will only be measured on participants in the Aim 3a phase of the study.

  Baseline and 4 weeks

Other Outcomes (1)

• Serum Surfactant Protein-A (SP-A, ng/mL)

  Up to 24 weeks

Study Arms (4)

Community based Multi-Ethnic Study of Atherosclerosis (MESA)

NO INTERVENTION

This cohort includes biospecimens collected from 1852 participants in the MESA sleep study \[Chen et al\]. Serum biomarkers were measured by immunoassay in the Laboratory for Clinical Biochemistry Research at the University of Vermont. All participants in this cohort will be analyzed for only the Aim 1 outcome measures.

HeartBEAT and BestAir

NO INTERVENTION

The cohort includes 62 men and 20 women with newly diagnosed moderate-to-severe OSA and without known severe lung disease, who had participated in either of two randomized trials of PAP therapy, the HeartBEAT \[Gottlieb et al\] and BestAIR \[Bakker et al\] studies. Participants were selected for this analysis based on mean PAP adherence of ≥4 hours daily over a follow-up period of 3 months in the HeartBEAT study and 6 months in the BestAIR study. Morning serum samples drawn at baseline and at the end of the PAP treatment period were assayed using commercially available ELISA for each biomarker in the Laboratory for Clinical Biochemistry Research at the University of Vermont Larner College of Medicine. All participants in this cohort will be analyzed for only the Aim 2 outcome measures.

CPAP treatment of OSA

EXPERIMENTAL

Participants with obstructive sleep apnea (OSA) will be treated with continuous positive airway pressure therapy (CPAP). All participants in this cohort will be analyzed for only the Aim 3a outcome measures.

Device: Continuous positive airway pressure (CPAP) therapy

ILD screening for OSA

EXPERIMENTAL

Participants with interstitial lung disease (ILD) will be screened for OSA by polysomnography. All participants in this cohort will be analyzed for only the Aim 3b outcome measures.

Device: Nox A1 Recorder

Interventions

Continuous positive airway pressure (CPAP) therapy DEVICE

Standard, clinically used CPAP therapy. CPAP will be prescribed by the participants' clinician provider and not by the study investigators.

CPAP treatment of OSA

Nox A1 Recorder DEVICE

Non-invasive, body-worn, sleep recording device for nocturnal polysomnography.

ILD screening for OSA

Eligibility Criteria

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

You may qualify if:

• Ability to provide informed consent.
• Age 18 years or greater
• Diagnosis of any of the following fibrotic interstitial lung diseases as defined by ATS/ERS/JRS/ALAT guidelines and research statements and Delphi surveys:
• Idiopathic pulmonary fibrosis
• Idiopathic non-specific interstitial pneumonia (NSIP) with fibrosis
• Chronic hypersensitivity pneumonitis with fibrosis
• Connective tissue disease related interstitial lung disease (CTD-ILD)
• Unclassifiable idiopathic interstitial pneumonia with fibrosis

You may not qualify if:

• Clinically significant lung disease other than fibrotic interstitial lung disease
• Planned change to the IPF treatment during the study period
• Current cigarette smoking (past 4 weeks)
• Lower respiratory tract infection in past 60 days. (Upper respiratory tract infection is not a contraindication)
• History of life-threatening cardiac arrhythmias
• Known chronic heart failure (LVEF \< 45% or echo evidence of RV dysfunction or PH)
• Chronic opiate analgesic use
• History of sleepiness-related automobile accident within past year of enrollment
• Expected survival time in the opinion of the investigator of less than 6 months
• History of stroke or spinal cord injury
• Age 18 years or greater
• Clinical diagnosis of untreated OSA documented by nocturnal polysomnography
• Current treatment with CPAP or oral appliance

Sponsors & Collaborators

• Columbia University: lead
• National Heart, Lung, and Blood Institute (NHLBI): collaborator

Study Sites (2)

Brigham & Women's Hospital

Boston, Massachusetts, 02115, United States

Location

Columbia University Medical Center

New York, New York, 10032, United States

Location

Related Publications (3)

• Chen X, Wang R, Zee P, Lutsey PL, Javaheri S, Alcantara C, Jackson CL, Williams MA, Redline S. Racial/Ethnic Differences in Sleep Disturbances: The Multi-Ethnic Study of Atherosclerosis (MESA). Sleep. 2015 Jun 1;38(6):877-88. doi: 10.5665/sleep.4732.

  PMID: 25409106 BACKGROUND

• Gottlieb DJ, Punjabi NM, Mehra R, Patel SR, Quan SF, Babineau DC, Tracy RP, Rueschman M, Blumenthal RS, Lewis EF, Bhatt DL, Redline S. CPAP versus oxygen in obstructive sleep apnea. N Engl J Med. 2014 Jun 12;370(24):2276-85. doi: 10.1056/NEJMoa1306766.

  PMID: 24918372 BACKGROUND

• Bakker JP, Wang R, Weng J, Aloia MS, Toth C, Morrical MG, Gleason KJ, Rueschman M, Dorsey C, Patel SR, Ware JH, Mittleman MA, Redline S. Motivational Enhancement for Increasing Adherence to CPAP: A Randomized Controlled Trial. Chest. 2016 Aug;150(2):337-45. doi: 10.1016/j.chest.2016.03.019. Epub 2016 Mar 24.

  PMID: 27018174 BACKGROUND

MeSH Terms

Conditions

Lung Diseases, Interstitial; Sleep Apnea, Obstructive

Interventions

Continuous Positive Airway Pressure; Therapeutics

Condition Hierarchy (Ancestors)

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

Intervention Hierarchy (Ancestors)

Positive-Pressure Respiration; Respiration, Artificial; Airway Management; Respiratory Therapy

Results Point of Contact

• Title: Sanja Jelic, MD
• Organization: Columbia University

sj366@cumc.columbia.edu

212-543-8875

Publication Agreements

• PI is Sponsor Employee: No
• Restrictive Agreement: No

Study Design

• Study Type: interventional
• Phase: not applicable
• Allocation: NON RANDOMIZED
• Masking: NONE
• Masking Details: None (Open Label)
• Purpose: TREATMENT
• Intervention Model: SEQUENTIAL
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Associate Professor of Medicine

Study Record Dates

• First Submitted: April 2, 2019
• First Posted: April 3, 2019
• Study Start: January 1, 2023
• Primary Completion: October 16, 2023
• Study Completion: October 16, 2023
• Last Updated: December 20, 2024
• Results First Posted: December 20, 2024

Record last verified: 2024-12

Data Sharing

• IPD Sharing: Will share
• Shared Documents: STUDY PROTOCOL
• Time Frame: Data will be available no later than 3 years after last research subject is enrolled in the study.
• Access Criteria: Researchers will be required to submit a written request to the Study PI describing the use of the specimens. The researcher must also document IRB approval and sign a material transfer agreement. The Study PI will make all decisions about use of the specimens. No identifiable information will be released, only coded samples and non-identifiable clinical/demographic information.

Locations

US (2)