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| ID | Type | Description | Link |
|---|---|---|---|
| 1R01HL137234-01 | U.S. NIH Grant/Contract | View source |
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Enrollment challenges
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| Name | Class |
|---|---|
| National Heart, Lung, and Blood Institute (NHLBI) | NIH |
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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).
This study is comprised of 3 aims:
Aim 1: Determine whether the greater OSA severity is associated with higher levels of serum biomarkers of AEC and endothelial injury and ECM remodeling in community-dwelling adults. This is a retrospective study that will analyze biospecimens from those who participated in the MESA sleep study [Chen et al].
Aim 2: Determine whether CPAP use is associated with reductions in alveolar epithelial cell (AEC) injury and endothelial injury, and extracellular matrix (ECM) remodeling biomarkers in adults with moderate-to-severe OSA. This is a retrospective study that will analyze biospecimens from those who participated in either the HeartBEAT [Gottlieb et al] and BestAIR [Bakker et al] studies.
Revised Aim 3: a) Determine whether untreated OSA promotes AEC and endothelial injury and ECM remodeling biomarkers in adults with ILD and OSA compared with those without OSA; b) Determine prospectively whether clinically-initiated 4-week PAP therapy increases markers of alveolar endothelial lung injury in OSA. Participants will be recruited at Columbia University and be assigned CPAP therapy as an intervention.
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| Label | Type | Description | Intervention Names |
|---|---|---|---|
| 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. |
|
| 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. |
| Name | Type | Description | Arm Group Labels | Other Names |
|---|---|---|---|---|
| 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. |
| Measure | Description | Time Frame |
|---|---|---|
| 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 |
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| Measure | Description | Time Frame |
|---|---|---|
| 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 |
Inclusion Criteria for Patients with ILD:
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:
Exclusion criteria for Patients with ILD:
Inclusion criteria for OSA patients:
Exclusion criteria for OSA patients:
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| Facility | Status | City | State | ZIP | Country | Contacts |
|---|---|---|---|---|---|---|
| Brigham & Women's Hospital | Boston | Massachusetts | 02115 | United States | ||
| Columbia University Medical Center |
| PubMed Identifier | Type | Citation | Retractions |
|---|---|---|---|
| 25409106 | Background | 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. | |
| 24918372 | 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. |
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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.
Data will be available no later than 3 years after last research subject is enrolled in the study.
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.
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Recruitment for Aim 3b of the study was terminated before any prospective participants could be enrolled.
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| ID | Title | Description |
|---|---|---|
| FG000 | Community Based Multi-Ethnic Study of Atherosclerosis (MESA) | 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. |
| FG001 | HeartBEAT and BestAir | This 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. |
| FG002 | CPAP Treatment of OSA | Participants with obstructive sleep apnea (OSA) will be treated with continuous positive airway pressure therapy (CPAP). |
| FG003 | ILD Screening for OSA | Participants with interstitial lung disease (ILD) will be screened for OSA by polysomnography. |
| Title | Milestones | Reasons Not Completed | ||||||||||||
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Aim 1 |
| |||||||||||||
| Aim 2 |
| |||||||||||||
| Aim 3a |
| |||||||||||||
| Aim 3b |
|
No participants were enrolled for Aim 3b.
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| ID | Title | Description |
|---|---|---|
| BG000 | Aim 1 Cohort: MESA | 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. |
| BG001 | Aim 2 Cohort: HeartBEAT and BestAir |
| Units | Counts |
|---|---|
| Participants |
|
| Title | Description | Population Description | Parameter Type | Dispersion Type | Unit of Measure | Calculate Percentage | Denominator Units Selected | Denominators | Classes |
|---|---|---|---|---|---|---|---|---|---|
| Age, Continuous | Mean |
| Type | Title | Description | Population Description | Reporting Status | Anticipated Posting Date | Parameter Type | Dispersion Type | Unit of Measure | Calculate Percentage | Time Frame | Units Analyzed | Denominator Units Selected | Arm/Group Information | Denominators | Classes | Analyses | ||||||||
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Primary | 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. | Posted | Mean | Standard Deviation | pg/mL | 1 day |
|
|
Up to 24 weeks
Adverse events were not collected from the Aim 3b cohort due to early study termination.
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| ID | Title | Description | Deaths (Affected) | Deaths (At Risk) | Serious Events (Affected) | Serious Events (At Risk) | Other Events (Affected) | Other Events (At Risk) |
|---|---|---|---|---|---|---|---|---|
| EG000 | Aim 1 Cohort: MESA | 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. |
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| Title | Organization | Phone | Extension | |
|---|---|---|---|---|
| Sanja Jelic, MD | Columbia University | 212-543-8875 | sj366@cumc.columbia.edu |
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| Type | Includes Protocol | Includes SAP | Includes ICF | Document Label | Document Date | Document Uploaded Date | Document File Name |
|---|---|---|---|---|---|---|---|
| Prot_SAP | Yes | Yes | No | Study Protocol and Statistical Analysis Plan | Jun 3, 2024 | Nov 14, 2024 | Prot_SAP_000.pdf |
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| ID | Term |
|---|---|
| D017563 | Lung Diseases, Interstitial |
| D020181 | Sleep Apnea, Obstructive |
| ID | Term |
|---|---|
| D008171 | Lung Diseases |
| D012140 | Respiratory Tract Diseases |
| D012891 | Sleep Apnea Syndromes |
| D001049 | Apnea |
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Not provided
| ID | Term |
|---|---|
| D045422 | Continuous Positive Airway Pressure |
| D013812 | Therapeutics |
| ID | Term |
|---|---|
| D011175 | Positive-Pressure Respiration |
| D012121 | Respiration, Artificial |
| D058109 | Airway Management |
| D012138 | Respiratory Therapy |
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Not provided
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None (Open Label)
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|
| Nox A1 Recorder | Device | Non-invasive, body-worn, sleep recording device for nocturnal polysomnography. |
|
| 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 |
| New York |
| New York |
| 10032 |
| United States |
| 27018174 | 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. |
| COMPLETED |
|
| NOT COMPLETED |
|
| COMPLETED |
|
| NOT COMPLETED |
|
| COMPLETED |
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| NOT COMPLETED |
|
This 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. |
| BG002 | Aim 3a Cohort: CPAP Treatment of OSA | Participants with OSA will be treated with CPAP. |
| BG003 | Aim 3b Cohort: ILD Screening for OSA | Participants with ILD will be screened for OSA by polysomnography. |
| BG004 | Total | Total of all reporting groups |
| years |
|
| Sex: Female, Male | Count of Participants | Participants |
|
| Race and Ethnicity Not Collected | Race and Ethnicity were not collected from any participant. | Count of Participants | Participants |
|
| Region of Enrollment | Count of Participants | Participants |
|
|
| Primary | 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. | Posted | Mean | Standard Deviation | pg/mL | 1 day |
|
|
|
| Primary | 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. | Posted | Mean | Standard Deviation | pg/mL | 1 day |
|
|
|
| Primary | 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. | Posted | Mean | Standard Deviation | pg/mL | 1 day |
|
|
|
| Primary | 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. | Posted | Mean | Standard Deviation | pg/mL | 1 day |
|
|
|
| Primary | 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. | Posted | Mean | 95% Confidence Interval | ng/mL | Baseline and post-CPAP follow-up, up to 24 Weeks |
|
|
|
| Primary | 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. | Posted | Mean | 95% Confidence Interval | ng/mL | Baseline and post-CPAP follow-up, up to 24 Weeks |
|
|
|
| Primary | 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. | Posted | Mean | 95% Confidence Interval | ng/mL | Baseline and post-CPAP follow-up, up to 24 Weeks |
|
|
|
| Primary | 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. | Posted | Mean | 95% Confidence Interval | ng/mL | Baseline and post-CPAP follow-up, up to 24 Weeks |
|
|
|
| Primary | 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. | Posted | Mean | Standard Deviation | pg/mL | Baseline and 4 weeks |
|
|
|
| Other Pre-specified | Serum Surfactant Protein-A (SP-A, ng/mL) | The between-arm difference in the longitudinal changes of SP-A will be measured. | Data was not collected thus cannot be analyzed. | Posted | Up to 24 weeks |
|
|
| 0 |
| 1,852 |
| 0 |
| 1,852 |
| 0 |
| 1,852 |
| EG001 | Aim 2 Cohort: HeartBEAT and BestAir | This 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. | 0 | 82 | 0 | 82 | 0 | 82 |
| EG002 | Aim 3a Cohort: CPAP Treatment of OSA | Participants with OSA will be treated with CPAP. | 0 | 87 | 0 | 87 | 0 | 87 |
| EG003 | Aim 3b Cohort: ILD Screening for OSA | Participants with ILD will be screened for OSA by polysomnography. | 0 | 0 | 0 | 0 | 0 | 0 |
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| D012120 |
| Respiration Disorders |
| D020919 | Sleep Disorders, Intrinsic |
| D020920 | Dyssomnias |
| D012893 | Sleep Wake Disorders |
| D009422 | Nervous System Diseases |
| Male |
|