Identification of Biomarkers of Obstructive Sleep Apnea.

Official title

Identification of Biomarkers to Understand the Pathogenesis of Obstructive Sleep Apnea.

Overview

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.

Detailed description

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.

Interventions

• Device Positive Airway Pressure (PAP) Therapy
  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.

Primary outcome measures

• Difference in blood biomarker concentrations between participants with obstructive sleep apnea (OSA) and non-OSA controls at baseline [Time frame: At enrollment, prior to initiation of PAP therapy (baseline, Month 0).]
• Change in blood biomarker concentrations in OSA participants after positive airway pressure (PAP) therapy. [Time frame: Baseline, 3 months and 6 months.]

Secondary outcome measures (5)

• Correlation between baseline blood biomarker concentrations and OSA severity (AHI) [Time frame: 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. [Time frame: 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 [Time frame: 3 months and 6 months]
• Stability of blood biomarker concentrations in untreated OSA (3-month observation period). [Time frame: Baseline and 3 months (Delay-TG)]
• Differences in serum and plasma metabolomic profiles between OSA and controls and in response to PAP therapy. [Time frame: Baseline, 3 months and 6 months]

Eligibility criteria

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.

Criteria are shown verbatim from the registry (in English). Final eligibility is always assessed by the study center.

Healthy volunteers: Yes

Study design

Allocation

Randomized

Model

Parallel assignment

Masking

Open label

Primary purpose

Diagnostic

Study locations

Poland · 1 center

• Department of Otolaryngology, Medical University of Bialystok — Bialystok

Publications

• 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. PMID 36430593
• 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. PMID 36504723
• 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. PMID 30678164
• 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. PMID 39336926
• 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. PMID 38610848
• 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. PMID 38256636
• 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. PMID 30828637
• 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. PMID 31300334

Identifiers

NCT: NCT07723144 · 2024/55/B/NZ7/00418

Primary sources (government registries)

• ClinicalTrials.gov (US NIH)

View this study on ClinicalTrials.gov ↗