Assessment of Continuous Positive Airway Pressure Therapy in OSA and ILD
试验速览
- 阶段
- 不适用
- 状态
- 终止
- 入组人数
- 2,021
- 试验地点
- 2
- 主要终点
- Angiopoietin-2 [Aim 1]
研究概览
简要总结
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).
详细描述
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.
研究设计
- 研究类型
- Interventional
- 分配方式
- Non Randomized
- 干预模型
- Sequential
- 主要目的
- Treatment
- 盲法
- None
盲法说明
None (Open Label)
入排标准
- 年龄范围
- 18 Years 至 —（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •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:
- •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
排除标准
- •for Patients with ILD:
- •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
- •Inclusion criteria for OSA patients:
- •Age 18 years or greater
- •Clinical diagnosis of untreated OSA documented by nocturnal polysomnography
- •Exclusion criteria for OSA patients:
- •Current treatment with CPAP or oral appliance
- •Identical exclusion criteria as for ILD patients
研究组 & 干预措施
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.
All participants in this cohort will be analyzed for only the Aim 1 outcome measures.
HeartBEAT and BestAir
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
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.
干预措施: Continuous positive airway pressure (CPAP) therapy (Device)
ILD screening for OSA
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.
干预措施: Nox A1 Recorder (Device)
结局指标
主要结局
Angiopoietin-2 [Aim 1]
时间窗: 1 day
This Outcome is specific to Aim 1 and will only be measured on participants in the Aim 1 phase of the study.
Serum Angiopoietin-2 (Ang-2, ng/mL) [Aim 3a]
时间窗: Baseline and 4 weeks
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.
Surfactant Protein D (SP-D) [Aim 1]
时间窗: 1 day
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.
E-selectin [Aim 1]
时间窗: 1 day
This Outcome is specific to Aim 1 and will only be measured on participants in the Aim 1 phase of the study.
Vascular Endothelial Growth Factor-A (VEGF-A) [Aim 1]
时间窗: 1 day
This Outcome is specific to Aim 1 and will only be measured on participants in the Aim 1 phase of the study.
Angiopoietin-interacting Soluble Tie-2 (sTie2) [Aim 1]
时间窗: 1 day
This Outcome is specific to Aim 1 and will only be measured on participants in the Aim 1 phase of the study.
Change in Serum Matrix Metalloproteinase-7 (MMP-7) Following CPAP [Aim 2]
时间窗: Baseline and post-CPAP follow-up, up to 24 Weeks
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.
Change in Serum Surfactant Protein-D (SP-D) Following CPAP [Aim 2]
时间窗: Baseline and post-CPAP follow-up, up to 24 Weeks
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.
Change in Serum Angiopoietin-2 (Ang-2) Following CPAP [Aim 2]
时间窗: Baseline and post-CPAP follow-up, up to 24 Weeks
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.
Change in Serum Osteopontin Following CPAP [Aim 2]
时间窗: Baseline and post-CPAP follow-up, up to 24 Weeks
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.
次要结局
未报告次要终点
研究者
Sanja Jelic
Associate Professor of Medicine
Columbia University