Identification of Biomarkers to Understand the Pathogenesis of Obstructive Sleep Apnea.
试验速览
- 阶段
- 不适用
- 状态
- 招募中
- 发起方
- 入组人数
- 120
- 试验地点
- 1
- 主要终点
- Difference in blood biomarker concentrations between participants with obstructive sleep apnea (OSA) and non-OSA controls at baseline
研究概览
简要总结
Obstructive sleep apnea (OSA) is a common sleep disorder associated with intermittent hypoxia, systemic inflammation, oxidative stress, and an increased risk of cardiovascular and metabolic diseases. Current diagnostic methods are effective but have limited availability and do not adequately predict disease burden or treatment response.
The purpose of this study is to identify and validate blood biomarkers that may improve the screening, diagnosis, risk stratification, and monitoring of adults with OSA. A total of 120 participants will undergo clinical evaluation and overnight polysomnography. Participants with moderate-to-severe OSA will be randomly assigned to either immediate or delayed positive airway pressure (PAP) therapy, while participants without OSA will serve as controls. Blood samples will be collected at predefined time points and analyzed for inflammatory, metabolic, oxidative stress, and other candidate biomarkers.
The study aims to determine which biomarkers are associated with OSA severity and how they change in response to PAP therapy. The results may contribute to the development of more accessible and personalized diagnostic and monitoring strategies for patients with OSA.
详细描述
Obstructive sleep apnea (OSA) is a highly prevalent disorder characterized by recurrent upper airway obstruction during sleep, resulting in intermittent hypoxia, sleep fragmentation, oxidative stress, systemic inflammation, endothelial dysfunction, and metabolic disturbances. Untreated OSA is associated with an increased risk of cardiovascular disease, diabetes mellitus, stroke, impaired quality of life, and all-cause mortality. Despite the availability of polysomnography as the reference diagnostic method, current diagnostic approaches have limited accessibility and do not adequately reflect disease burden or predict treatment response.
The primary objective of this study is to identify and validate blood biomarkers associated with the presence, severity, and treatment response of OSA. The investigators hypothesize that selected circulating proteins, inflammatory mediators, oxidative stress markers, and metabolic profiles can improve the screening, diagnosis, risk stratification, and monitoring of patients with OSA.
A total of 120 adults will undergo standardized clinical evaluation and overnight polysomnography. Participants diagnosed with moderate-to-severe OSA will be randomly assigned to either immediate or delayed initiation of positive airway pressure (PAP) therapy, whereas participants without OSA will serve as the control group. Blood samples will be collected at predefined study visits to evaluate changes in candidate biomarkers before and during treatment.
The study will investigate a broad panel of biomarkers representing inflammatory pathways, endothelial dysfunction, oxidative stress, and metabolomic alterations using validated laboratory techniques, including multiplex immunoassays, enzyme-linked immunosorbent assays (ELISA), and metabolomic analyses. Changes in biomarker profiles will be evaluated in relation to OSA severity and response to PAP therapy.
The results of this study are expected to improve the understanding of the biological mechanisms underlying OSA and facilitate the development of novel biomarker-based approaches for screening, diagnosis, disease monitoring, and personalized management of patients with obstructive sleep apnea.
研究设计
- 研究类型
- Interventional
- 分配方式
- Randomized
- 干预模型
- Parallel
- 主要目的
- Diagnostic
- 盲法
- None
入排标准
- 年龄范围
- 18 Years 至 65 Years（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 是
入选标准
- •Participants with obstructive sleep apnea (OSA):
- •Age 18 to 65 years.
- •Moderate or severe obstructive sleep apnea confirmed by overnight polysomnography (apnea-hypopnea index [AHI] ≥15 events/hour).
- •Willing and able to provide written informed consent.
- •Willing to undergo repeated blood sampling and study assessments.
- •Willing to use positive airway pressure (PAP) therapy and accept random assignment to immediate or delayed treatment.
- •Control participants:
- •Age 18 to 65 years.
- •No obstructive sleep apnea (AHI <5 events/hour on overnight polysomnography).
- •Willing and able to provide written informed consent.
- •Willing to undergo study assessments and blood sampling.
排除标准
- •Mild obstructive sleep apnea (AHI 5 to <15 events/hour).
- •Central sleep apnea.
- •Previous treatment for obstructive sleep apnea within the previous 3 months.
- •Body mass index (BMI) ≥40 kg/m².
- •Severe cardiovascular disease.
- •Severe kidney disease or impaired renal function.
- •Significant liver disease.
- •Chronic inflammatory, autoimmune, or rheumatic disease.
- •Active cancer or other condition associated with systemic inflammation.
- •Chronic respiratory diseases, including asthma or chronic obstructive pulmonary disease.
- •Respiratory infection within 4 weeks before enrollment.
- •Major surgery or significant injury within the previous 3 months.
- •Chronic rhinosinusitis.
- •Current treatment with systemic corticosteroids, immunosuppressive drugs, cytotoxic drugs, chronic anti-inflammatory medications, or other medications that may influence inflammatory biomarkers.
- •Pregnancy or any condition that, in the opinion of the investigators, would make participation unsafe or interfere with interpretation of the study results.
研究组 & 干预措施
Early Positive Airway Pressure (PAP) Therapy
Participants with moderate-to-severe obstructive sleep apnea receive positive airway pressure (PAP) therapy immediately after randomization and continue treatment for 6 months. Clinical assessments and blood samples are obtained at baseline, 3 months, and 6 months.
干预措施: Positive Airway Pressure (PAP) Therapy (Device)
Delayed Positive Airway Pressure (PAP) Therapy
Participants with moderate-to-severe obstructive sleep apnea do not receive PAP therapy during the first 3 months after randomization. PAP therapy is initiated after the 3-month evaluation and continued for the following 3 months. Clinical assessments and blood samples are obtained at baseline, 3 months, and 6 months.
干预措施: Positive Airway Pressure (PAP) Therapy (Device)
Control Group
Participants without obstructive sleep apnea undergo baseline clinical evaluation, overnight polysomnography, and blood sampling. No PAP therapy or study intervention is administered.
结局指标
主要结局
Difference in blood biomarker concentrations between participants with obstructive sleep apnea (OSA) and non-OSA controls at baseline
时间窗: At enrollment, prior to initiation of PAP therapy (baseline, Month 0).
Comparison of baseline serum and plasma concentrations of a predefined panel of circulating protein biomarkers (osteoprotegerin, cardiotrophin-1, chitinase-3-like protein 1/YKL-40, CRP, HbA1c, erythropoietin, thioredoxin, PD-L1) and a predefined multiplex panel of 48 cytokines, chemokines and growth factors, measured by ELISA and multiplex ELISA (Luminex), between adults with moderate-to-severe OSA (AHI \>=15) and non-OSA controls (AHI \<5) defined by polysomnography. Results will be reported in assay-appropriate units, including pg/mL, ng/mL, mg/L, or percentage, as applicable.
Change in blood biomarker concentrations in OSA participants after positive airway pressure (PAP) therapy.
时间窗: Baseline, 3 months and 6 months.
Change from baseline in serum and plasma concentrations of the predefined biomarker panel after positive airway pressure (PAP) therapy. In the Early Treatment Group change is assessed after 3 and 6 months of continuous PAP; in the Delay-TG after 3 months of PAP delivered between months 3 and 6. Aim: determine whether and to what degree biomarker values change in response to standard OSA treatment.
次要结局
- Correlation between baseline blood biomarker concentrations and OSA severity (AHI)(At enrollment, prior to initiation of PAP therapy (baseline, Month 0).)
- Normalization of blood biomarker concentrations toward control values after PAP therapy in OSA participants.(Control: baseline; Early-TG: Month 3 and Month 6; Delay-TG: Month 6.)
- Effect of PAP treatment duration (3 vs 6 months) on blood biomarker concentrations(3 months and 6 months)
- Stability of blood biomarker concentrations in untreated OSA (3-month observation period).(Baseline and 3 months (Delay-TG))
- Differences in serum and plasma metabolomic profiles between OSA and controls and in response to PAP therapy.(Baseline, 3 months and 6 months)