Identification of Biomarkers of Obstructive Sleep Apnea.
Identification of Biomarkers to Understand the Pathogenesis of Obstructive Sleep Apnea.
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.
調査の概要
状態
詳細な説明
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.
研究の種類
入学 (推定)
段階
- 適用できない
連絡先と場所
研究連絡先
- 名前：Ewa Olszewska, M.D., Prof.
- 電話番号：+48 85 831 82 69
- メール：ewa.olszewska@umb.edu.pl
研究連絡先のバックアップ
- 名前：Agnieszka Polecka, M.D.
- 電話番号：+48 85 831 82 69
- メール：agnieszka.polecka@umb.edu.pl
研究場所
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Podlaskie Voivodeship
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Bialystok、Podlaskie Voivodeship、ポーランド、15-276
- 募集
- Department of Otolaryngology, Medical University of Bialystok
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コンタクト：
- Ewa Olszewska, M.D., Prof.
- 電話番号：+48 85 831 82 69
- メール：ewa.olszewska@umb.edu.pl
-
コンタクト：
- Agnieszka Polecka, M.D.
- 電話番号：+48 85 831 82 69
- メール：agnieszka.polecka@umb.edu.pl
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参加基準
適格基準
就学可能な年齢
- 大人
- 高齢者
健康ボランティアの受け入れ
説明
Inclusion Criteria:
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.
Exclusion Criteria:
- 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.
研究計画
研究はどのように設計されていますか？
デザインの詳細
- 主な目的：診断
- 割り当て：ランダム化
- 介入モデル：並列代入
- マスキング：なし（オープンラベル）
武器と介入
参加者グループ / アーム |
介入・治療 |
|---|---|
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実験的：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.
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Positive airway pressure (PAP) therapy will be administered according to current clinical practice guidelines for the treatment of obstructive sleep apnea.
PAP settings will be individually titrated based on clinical assessment and sleep study findings to ensure effective treatment.
Participants assigned to PAP therapy will use the device during sleep for the duration specified in the study protocol.
Adherence to therapy will be monitored using device-recorded usage data.
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実験的：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.
|
Positive airway pressure (PAP) therapy will be administered according to current clinical practice guidelines for the treatment of obstructive sleep apnea.
PAP settings will be individually titrated based on clinical assessment and sleep study findings to ensure effective treatment.
Participants assigned to PAP therapy will use the device during sleep for the duration specified in the study protocol.
Adherence to therapy will be monitored using device-recorded usage data.
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介入なし：Control Group
Participants without obstructive sleep apnea undergo baseline clinical evaluation, overnight polysomnography, and blood sampling.
No PAP therapy or study intervention is administered.
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この研究は何を測定していますか？
主要な結果の測定
結果測定 |
メジャーの説明 |
時間枠 |
|---|---|---|
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Difference in blood biomarker concentrations between participants with obstructive sleep apnea (OSA) and non-OSA controls at baseline
時間枠：At enrollment, prior to initiation of PAP therapy (baseline, Month 0).
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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.
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At enrollment, prior to initiation of PAP therapy (baseline, Month 0).
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Change in blood biomarker concentrations in OSA participants after positive airway pressure (PAP) therapy.
時間枠：Baseline, 3 months and 6 months.
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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.
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Baseline, 3 months and 6 months.
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二次結果の測定
結果測定 |
メジャーの説明 |
時間枠 |
|---|---|---|
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Correlation between baseline blood biomarker concentrations and OSA severity (AHI)
時間枠：At enrollment, prior to initiation of PAP therapy (baseline, Month 0).
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Correlation between baseline concentrations of the studied blood biomarkers and OSA severity expressed by the apnea-hypopnea index (AHI), as well as mean and lowest nocturnal oxygen saturation, in OSA participants.
Goal: evaluate suitability of biomarkers for grading OSA severity.
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At enrollment, prior to initiation of PAP therapy (baseline, Month 0).
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Normalization of blood biomarker concentrations toward control values after PAP therapy in OSA participants.
時間枠：Control: baseline; Early-TG: Month 3 and Month 6; Delay-TG: Month 6.
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Comparison of post-PAP-treatment biomarker concentrations in OSA participants (Early-TG and Delay-TG) with the enrollment values of the non-OSA control group, to assess whether treatment shifts biomarker values toward those of healthy controls.
Goal: identify biomarkers specific to OSA-related hypoxia that approach the concentrations observed in participants without OSA.
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Control: baseline; Early-TG: Month 3 and Month 6; Delay-TG: Month 6.
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Effect of PAP treatment duration (3 vs 6 months) on blood biomarker concentrations
時間枠：3 months and 6 months
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Assessment of the impact of PAP treatment duration on biomarker values: (a) comparison of post-treatment values between the Early Treatment Group (6 months of PAP) and the Delay Treatment Group (3 months of PAP); (b) within Early-TG, comparison of values after 3 versus 6 months to evaluate whether changes become more robust with continued treatment.
Goal: determine whether longer therapy produces greater biomarker change.
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3 months and 6 months
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Stability of blood biomarker concentrations in untreated OSA (3-month observation period).
時間枠：Baseline and 3 months (Delay-TG)
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Comparison of biomarker concentrations in the Delay-TG between baseline and after the 3-month observation period without any treatment, to verify that biomarker values do not change spontaneously in the absence of PAP therapy.
Serves as the internal untreated reference for the treatment effect.
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Baseline and 3 months (Delay-TG)
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Differences in serum and plasma metabolomic profiles between OSA and controls and in response to PAP therapy.
時間枠：Baseline, 3 months and 6 months
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Targeted and untargeted metabolomic profiling (GC-MS and LC-QTOF-MS; amino acids, carbohydrates, fatty acids, and specific lipids including phosphatidylcholines, ceramides, triglycerides and lysophosphatidylcholines) compared between OSA participants and controls at baseline, and before versus after PAP therapy in OSA participants.
Goal: identify known and novel metabolite biomarkers of OSA.
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Baseline, 3 months and 6 months
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その他の成果指標
結果測定 |
メジャーの説明 |
時間枠 |
|---|---|---|
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Differences in blood biomarker concentrations between moderate and severe OSA subgroups.
時間枠：Baseline, 3 months and 6 months
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Comparison of biomarker concentrations between participants with moderate OSA (15<=AHI<30) and severe OSA (AHI>=30) at baseline and in response to PAP therapy.
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Baseline, 3 months and 6 months
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Differences in blood biomarker concentrations between BMI categories (normal weight, overweight, obese).
時間枠：Baseline, 3 months and 6 months
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Comparison of biomarker concentrations between body-mass-index categories (normal <25, overweight 25-<30, obese >=30) at baseline and in response to PAP therapy, to assess whether biomarker profile and treatment response differ by weight category.
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Baseline, 3 months and 6 months
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Differences in blood biomarker concentrations between female and male participants.
時間枠：Baseline, 3 months and 6 months
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Comparison of biomarker concentrations between female and male participants at baseline and in response to PAP therapy, to assess sex-related differences in biomarker profile and treatment response.
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Baseline, 3 months and 6 months
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Concentrations of oxidative stress biomarkers in OSA participants and controls
時間枠：Baseline, 3 months and 6 months
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Assessment of protein, lipid and DNA oxidation products: advanced oxidation protein products (AOPP, colorimetric method), ischemia-modified albumin, advanced glycation end products, 3-nitrotyrosine, 4-hydroxynonenal, 8-isoprostanes and 8-hydroxy-2-deoxyguanosine (ELISA), compared between OSA and controls at baseline and before versus after PAP therapy.
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Baseline, 3 months and 6 months
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協力者と研究者
出版物と役立つリンク
一般刊行物
- Peppard PE, Young T, Barnet JH, Palta M, Hagen EW, Hla KM. Increased prevalence of sleep-disordered breathing in adults. Am J Epidemiol. 2013 May 1;177(9):1006-14. doi: 10.1093/aje/kws342. Epub 2013 Apr 14.
- Benjafield AV, Ayas NT, Eastwood PR, Heinzer R, Ip MSM, Morrell MJ, Nunez CM, Patel SR, Penzel T, Pepin JL, Peppard PE, Sinha S, Tufik S, Valentine K, Malhotra A. Estimation of the global prevalence and burden of obstructive sleep apnoea: a literature-based analysis. Lancet Respir Med. 2019 Aug;7(8):687-698. doi: 10.1016/S2213-2600(19)30198-5. Epub 2019 Jul 9.
- Olszewska E, Pietrewicz TM, Swiderska M, Jamiolkowski J, Chabowski A. A Case-Control Study on the Changes in High-Sensitivity C-Reactive Protein and Tumor Necrosis Factor-Alpha Levels with Surgical Treatment of OSAS. Int J Mol Sci. 2022 Nov 15;23(22):14116. doi: 10.3390/ijms232214116.
- Mohit, Tomar MS, Araniti F, Pateriya A, Singh Kushwaha RA, Singh BP, Jurel SK, Singh RD, Shrivastava A, Chand P. Identification of metabolic fingerprints in severe obstructive sleep apnea using gas chromatography-Mass spectrometry. Front Mol Biosci. 2022 Nov 21;9:1026848. doi: 10.3389/fmolb.2022.1026848. eCollection 2022.
- Kheirandish-Gozal L, Gozal D. Obstructive Sleep Apnea and Inflammation: Proof of Concept Based on Two Illustrative Cytokines. Int J Mol Sci. 2019 Jan 22;20(3):459. doi: 10.3390/ijms20030459.
- Olszewska E, De Vito A, Heiser C, Vanderveken O, O'Connor-Reina C, Baptista P, Kotecha B, Vicini C. Consensus Statements among European Sleep Surgery Experts on Snoring and Obstructive Sleep Apnea: Part 3 Palatal Surgery, Outcomes and Follow-Up, Complications, and Post-Operative Management. J Clin Med. 2024 Sep 13;13(18):5438. doi: 10.3390/jcm13185438.
- Olszewska E, De Vito A, O'Connor-Reina C, Heiser C, Baptista P, Kotecha B, Vanderveken O, Vicini C. Consensus Statements among European Sleep Surgery Experts on Snoring and Obstructive Sleep Apnea: Part 2 Decision-Making in Surgical Management and Peri-Operative Considerations. J Clin Med. 2024 Apr 3;13(7):2083. doi: 10.3390/jcm13072083.
- Olszewska E, De Vito A, Baptista P, Heiser C, O'Connor-Reina C, Kotecha B, Vanderveken O, Vicini C. Consensus Statements among European Sleep Surgery Experts on Snoring and Obstructive Sleep Apnea: Part 1 Definitions and Diagnosis. J Clin Med. 2024 Jan 16;13(2):502. doi: 10.3390/jcm13020502.
- Olszewska E, Woodson BT. Palatal anatomy for sleep apnea surgery. Laryngoscope Investig Otolaryngol. 2019 Jan 10;4(1):181-187. doi: 10.1002/lio2.238. eCollection 2019 Feb.
- Olszewska, E., Chrapanie i Bezdechy. Diagnostyka i Leczenie [Snoring and Apnea. Diagnosis and Treatment] 2019, Warszawa: Medipage
研究記録日
主要日程の研究
研究開始 (実際)
一次修了 (推定)
研究の完了 (推定)
試験登録日
最初に提出
QC基準を満たした最初の提出物
最初の投稿 (実際)
学習記録の更新
投稿された最後の更新 (実際)
QC基準を満たした最後の更新が送信されました
最終確認日
詳しくは
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追加の関連 MeSH 用語
その他の研究ID番号
- 2024/55/B/NZ7/00418
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