Assessment of Continuous Positive Airway Pressure Therapy in IPF (ACT-IPF)

The purpose of this study is to evaluate whether biomarkers of lung injury and remodeling are responsive to effective continuous positive airway pressure (CPAP) treatment in adults with idiopathic pulmonary fibrosis (IPF) and moderate-to-severe obstructive sleep apnea (OSA).

Study Overview

• Status: Recruiting
• Conditions: Obstructive Sleep Apnea; Interstitial Lung Disease
• Intervention / Treatment: Device: Auto-CPAP; Other: Withdrawal of Auto-CPAP

Detailed Description

Idiopathic pulmonary fibrosis (IPF) is a progressive fibrotic disease of the peripheral lung parenchyma that affects 0.5% of older adults in the U.S. and confers a very poor median survival. Repetitive injury to the lung with abnormal healing likely results in fibrosis as treatment of those risk factors that cause these injuries may improve outcomes. Obstructive sleep apnea (OSA), a form of sleep disordered breathing, is highly prevalent in adults with IPF and may be a risk factor in IPF by exerting peripheral tractional stress on the lung and promoting oxidative injury by intermittent hypoxia. Effective treatment of OSA with continuous positive airway pressure (CPAP) reduces the number of obstructive events in OSA and therefore may reduce repetitive injury to the lung in adults with IPF.

Participants in this study will undergo polysomnography to determine whether they have OSA, and if so, its severity based on the apnea-hypopnea index (AHI, events/ hour). Those participants with moderate-to-severe OSA will undergo CPAP treatment for up to 48 weeks with an interim period of withdrawal of CPAP. The primary aim of this study will examine the effect of CPAP treatment and its withdrawal and re-initiation on biomarkers of lung injury and remodeling in adults with IPF and moderate-to-severe OSA who are adherent to CPAP (expected sample size for this group is 30). The study will stop enrollment after 30 participants in this group are enrolled.

• Study Type: Interventional
• Enrollment (Estimated): 165
• Phase: Not Applicable

Contacts and Locations

• Study Contact: Name: Alondra Jimenez Holguin; Phone Number: 212-342-0256; Email: aj2886@cumc.columbia.edu
• Study Contact Backup: Name: Sanja Jelic, MD; Email: sj366@cumc.columbia.edu

Study Locations

• United States
  • New York
    • New York, New York, United States, 10032
      • Recruiting
      • Columbia University Medical Center
      • Contact: Alondra Jimenez Holguin; Phone Number: 212-342-0256; Email: aj2886@cumc.columbia.edu
      • Principal Investigator: Sanja Jelic, MD
      • Sub-Investigator: John S Kim, MD

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 50 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No

Description

Inclusion Criteria:

1. Informed consent
2. Age equal to or greater than 50 years
3. Diagnosis of IPF as defined by the 2018 ATS/ERS/JRS/ALAT guidelines

Exclusion Criteria:

1. Clinically significant lung disease other than IPF
2. Planned change to the IPF treatment during the study period
3. Known contraindication to CPAP
4. Current use of CPAP, an oral appliance, or hypoglossal nerve stimulation for treatment of OSA
5. Current cigarette smoking (past 4 weeks)
6. Lower respiratory tract infection in the past 60 days. (Upper respiratory tract infection is not a contraindication)
7. History of life-threatening cardiac arrhythmias
8. Known chronic heart failure (Left ventricle ejection fraction < 45% or echo evidence of right ventricle dysfunction or pulmonary hypertension)
9. Chronic opiate analgesic use
10. History of stroke or spinal cord injury
11. History of sleepiness-related automobile accident within past year of enrollment
12. Expected survival time in the opinion of the investigator of less than 6 months
13. Commercial driver's license or occupation

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Non-Randomized
• Interventional Model: Sequential Assignment
• Masking: None (Open Label)

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Other: Moderate to Severe OSA - treated; Moderate-to-severe OSA Treated with and adherent to Auto-CPAP	Device: Auto-CPAP; Use of Auto-CPAP
Experimental: Moderate to Severe OSA - withdrawal; Moderate-to-severe OSA Withdrawal of Auto-CPAP	Other: Withdrawal of Auto-CPAP; Withdrawal of Auto-CPAP

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Serum matrix metalloproteinase-7 (MMP-7, ng/mL)	The differences between-arm difference in the longitudinal changes of MMP-7 will be measured.	Up to 24 Weeks
Serum surfactant protein-D (SP-D, ng/mL)	The between-arm difference in the longitudinal changes of SP-D will be measured.	Up to 24 Weeks
Serum Angiopoietin-2 (Ang-2, ng/mL)	The between-arm difference in the longitudinal changes of Ang-2 will be measured.	Up to 48 Weeks
Serum surfactant protein-A (SP-A, ng/mL)	The between-arm difference in the longitudinal changes of SP-A will be measured.	Up to 24 weeks

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Forced vital capacity (FVC)	Forced vital capacity, or FVC, is defined as the amount of air which can be forcibly exhaled from the lungs after taking the deepest breath possible.	24 and 48 weeks
Diffusing capacity of the lung for carbon monoxide (DLCO)	Diffusing capacity of the lungs for carbon monoxide (DLCO) is a medical test that determines how much oxygen travels from the alveoli of the lungs to the blood stream.	24 and 48 weeks
Score on St. George's Respiratory Questionnaire (SGRQ)	The SGRQ is a 50-item questionnaire developed to measure health status (quality of life) in patients with diseases of airways obstruction. Scores range from 0 to 100, with higher scores indicating more limitations.	24 and 48 weeks
Score on University of California San Diego (USCD) Shortness of Breath Questionnaire (SOBQ)	The SOBQ is a a 24-item questionnaire that assesses self-reported shortness of breath while performing a variety of activities of daily living. Items are assessed on a 6-point scale (0 = "not at all" to 5 = "maximal or unable to do because of breathlessness") for a total score ranging from 0 to 120.	24 and 48 weeks
Score on Epworth Sleepiness Scale (ESS)	The ESS is a self-administered questionnaire with 8 questions. Respondents are asked to rate, on a 4-point scale (0-3), their usual chances of dozing off or falling asleep while engaged in eight different activities. The ESS score (the sum of 8 item scores, 0-3) can range from 0 to 24. The higher the ESS score, the higher that person's average sleep propensity in daily life (ASP), or their 'daytime sleepiness'.	24 and 48 weeks
Sleep Apnea Quality of Life Index (SAQLI)	The SAQLI is a 35-item questionnaire is used to assess obstructive sleep apnea-related quality of life (QOL). Items are assessed on a 7-point scale with 0 indicating "all the time" to 7 indicating "not at all".	24 and 48 weeks
Assess Quality of life in Idiopathic Pulmonary Fibrosis (ATAQ-IPF)	ATAQ-IPF is a 74-item questionnaire used to assess quality of life among adults with idiopathic pulmonary fibrosis.	24 and 48 weeks
Gastroesophageal Reflux Disease Questionnaire (GERD-Q)	GerdQ is a 6-item questionnaire to assess gastroesophageal reflux symptoms.	24 and 48 weeks
Cough Visual Analog Scale	Cough visual analog scale, a standardized scale ranging from 0 (no cough) to 100 (severe cough) on a continuous scale.	24 and 48 weeks

Other Outcome Measures

Outcome Measure	Measure Description	Time Frame
Concentration of CA125 (U/mL)	continuous measure in blood	Up to 48 Weeks
Concentration of CA19-9 (U/mL)	continuous measure in blood	Up to 48 Weeks
Concentration of Osteopontin (ng/mL)	continuous measure in blood	Up to 48 Weeks
Moderate to Severe OSA Non-Adherent to CPAP	We will examine primary and secondary outcomes in participants with 1. Moderate-to-severe OSA who are not adherent to CPAP 2. No or Mild OSA	Up to 10 years

Collaborators and Investigators

• Sponsor: Columbia University
• Collaborators: National Heart, Lung, and Blood Institute (NHLBI)
• Investigators: Principal Investigator: Sanja Jelic, MD, Columbia University; Study Chair: Daniel J Gottlieb, MD, Brigham and Women's Hospital

Study record dates

Study Major Dates

• Study Start (Actual): January 1, 2023
• Primary Completion (Estimated): December 31, 2024
• Study Completion (Estimated): December 31, 2025

Study Registration Dates

• First Submitted: April 2, 2019
• First Submitted That Met QC Criteria: April 2, 2019
• First Posted (Actual): April 3, 2019

Study Record Updates

• Last Update Posted (Actual): October 18, 2023
• Last Update Submitted That Met QC Criteria: October 17, 2023
• Last Verified: October 1, 2023

More Information

Terms related to this study

• Keywords: CPAP; Obstructive Sleep Apnea (OSA); Idiopathic Pulmonary Fibrosis (IPF); Interstitial Lung Disease (ILD)
• Additional Relevant MeSH Terms: Nervous System Diseases; Respiratory Tract Diseases; Apnea; Respiration Disorders; Sleep Disorders, Intrinsic; Dyssomnias; Sleep Wake Disorders; Sleep Apnea Syndromes; Sleep Apnea, Obstructive; Lung Diseases; Lung Diseases, Interstitial
• Other Study ID Numbers: AAAR6902; 1R01HL137234-01 (U.S. NIH Grant/Contract)

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: YES
• IPD Plan Description: Researchers will be required to submit a written request to the Study Principal Investigator (PI) describing the use of the specimens. The researcher must also document institutional review board (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 anonymized samples and non-identifiable clinical/demographic information. For genomic data generated from whole-exome sequencing, the genotype and relevant phenotype data for participants who consented to share data will be registered and shared through the database of Genotypes and Phenotypes (dbGaP), a controlled access database, once the sequencing data have been cleaned and quality control procedures are completed.
• IPD Sharing Time Frame: Data will be available no later than 3 years after last research subject is enrolled in the study.
• IPD Sharing 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.
• IPD Sharing Supporting Information Type: STUDY_PROTOCOL

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: Yes
• product manufactured in and exported from the U.S.: No