XOR Levels in OSA Patients (XOR-OSA) (XOR-OSA)

Obstructive Sleep Apnea Severity and Xanthine Oxidoreductase Activity: Mechanisms and Clinical Implications

The level of xanthine oxidoreductase (XOR) in plasma is associated with oxidative stress and inflammation. Obstructive Sleep Apnea (OSA) is characterized by repeated upper airway obstruction and apneas during sleep, leading to chronic intermittent hypoxemia. The specific role of XOR in OSA, its relationship with the severity of OSA, and the changes in XOR levels before and after CPAP treatment remain unclear. The study will enroll 80 patients from the First Affiliated Hospital of Nanjing Medical University, categorized by their Apnea-Hypopnea Index (AHI) into mild, moderate, and severe OSA groups. Participants will undergo baseline assessments including polysomnography (PSG) and measurements of XOR activity and biomarkers such as uric acid, endothelin-1 (ET-1), endothelial nitric oxide synthase (eNOS), and inflammatory markers. Eligible patients will receive CPAP treatment for 3 months, after which their XOR activity and biomarker levels will be re-evaluated to assess treatment efficacy.

Study Overview

• Status: Recruiting
• Conditions: Obstructive Sleep Apnea
• Intervention / Treatment: Device: CPAP Treatment

Detailed Description

Xanthine oxidoreductase (XOR) is an enzyme involved in the oxidative metabolism of purines, producing reactive oxygen species (ROS) as byproducts. Elevated XOR activity is associated with increased oxidative stress and inflammation. In patients with Obstructive Sleep Apnea(OSA), repeated episodes of hypoxia and reoxygenation lead to oxidative stress and inflammatory responses. However, the specific changes in XOR activity in OSA patients are not well understood.

This study aims to evaluate the effects of Continuous Positive Airway Pressure (CPAP) treatment on patients with OSA by analyzing XOR activity and related biomarkers. The primary objective is to assess the correlation between XOR activity levels and the severity of OSA, and to determine how these levels change following a 3-month CPAP intervention.

The study will enroll 80 patients aged 18-80 years from the First Affiliated Hospital of Nanjing Medical University. Participants will be diagnosed with OSA according to established guidelines, and must be first-time visitors with no prior OSA surgery or CPAP treatment history. Patients with severe cerebrovascular diseases, psychiatric conditions, diagnosed diabetes with significant vascular complications, severe COPD, pulmonary hypertension, heart failure, or pregnancy will be excluded.

All participants will undergo polysomnography (PSG) to determine the Apnea-Hypopnea Index (AHI) and categorize them into mild, moderate, or severe OSA groups.

Blood samples will be collected to measure baseline XOR activity and related biomarkers, including uric acid, endothelin-1 (ET-1), endothelial nitric oxide synthase (eNOS), C-reactive protein (CRP), tumor necrosis factor-alpha (TNF-α), interleukin-6 (IL-6), malondialdehyde (MDA), superoxide dismutase (SOD), hypoxia-inducible factor-1 (HIF-1), and angiotensin II (Ang II).

Eligible patients will receive CPAP therapy for a duration of 3 months. Patients unsuitable for CPAP therapy will receive alternative treatments such as upper airway surgery, oral appliances, or weight reduction programs. After 3 months of CPAP therapy, participants will undergo follow-up PSG to reassess sleep parameters. Blood samples will be collected again to measure changes in XOR activity and related biomarkers.

The data collected will be analyzed using SPSS software. Correlation analysis will be performed to assess the relationship between AHI, lowest SpO2, oxygen load, blood pressure load, ESS sleepiness scores, and XOR levels. Paired t-tests will be used to compare pre- and post-treatment XOR activity and biomarker levels. Repeated measures ANOVA will be conducted to evaluate the long-term changes and sustained effects of CPAP therapy.

This study aims to provide a comprehensive understanding of the biochemical impacts of CPAP therapy on patients with OSAHS. The findings are expected to identify potential biomarkers for assessing treatment efficacy and to guide future therapeutic strategies, ultimately improving patient outcomes in clinical practice.

• Study Type: Interventional
• Enrollment (Estimated): 80
• Phase: Not Applicable

Contacts and Locations

Study Locations

• China
  • Jiangsu
    • Nanjing, Jiangsu, China, 210029
      • Recruiting
      • The First Affiliated Hospital of Nanjing Medical University
      • Contact: Ning Ding, doctor; Phone Number: 86-25-68136723; Email: dr.ningding@live.cn
      • Principal Investigator: Ning Ding, doctor

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Adult; Older Adult
• Accepts Healthy Volunteers: No

Description

Inclusion Criteria:

1. Patients aged between 18 and 80 years.
2. Diagnosed with Obstructive Sleep Apnea Hypopnea Syndrome (OSAHS)(apnea-hypopnea index≥5/h).
3. First-time diagnosis, with no previous surgical interventions or CPAP treatment for OSA.
4. Ability and willingness to provide informed consent for participation in the study.

Exclusion Criteria:

1. History of severe stroke or cerebral hemorrhage, or presence of neurological or psychiatric conditions that could affect study results.
2. Presence of active malignancies or other severe underlying diseases, such as severe liver or kidney dysfunction. Diagnosed with diabetes or other significant vascular diseases.
3. Presence of severe chronic obstructive pulmonary disease (COPD), severe asthma, severe pulmonary hypertension, or heart failure caused by any condition.
4. Pregnancy or having other conditions that make participation in this study unsuitable.
5. Extremely debilitated patients or those with severe underlying conditions.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: N/A
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: CPAP Treatment Group; Patients with Obstructive Sleep Apnea Hypopnea Syndrome (OSAHS) who are eligible for Continuous Positive Airway Pressure (CPAP) therapy.	Device: CPAP Treatment; Continuous Positive Airway Pressure (CPAP) therapy will be administered to patients for 3 months. The CPAP device will be set to deliver a continuous flow of air at a prescribed pressure to keep the patient's airway open during sleep.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Xanthine Oxidoreductase (XOR) Activity	To measure changes in XOR activity levels in OSA patients with different severities, using enzyme-linked immunosorbent assay (ELISA) techniques, before and after 3 months of CPAP therapy, reported in units per liter (U/L).	Baseline and 3 months of CPAP therapy
Apnea-Hypopnea Index (AHI)	To measure changes in the Apnea-Hypopnea Index, quantifying the severity of sleep apnea, reported as the number of apneas and hypopneas per hour of sleep.	Baseline and 3 months of CPAP therapy.

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Uric Acid Levels	Assess changes in serum uric acid levels, reported in milligrams per deciliter (mg/dL), using ELISA.	Baseline and 3 months of CPAP therapy
Endothelial Nitric Oxide Synthase (eNOS) Activity	Measure changes in eNOS activity in serum, reported in units per liter (U/L), using ELISA.	Baseline and 3 months of CPAP therapy
C-Reactive Protein (CRP) Levels	Measure changes in C-reactive protein levels in serum, reported in milligrams per liter (mg/L), using ELISA.	Baseline and 3 months of CPAP therapy
Superoxide Dismutase (SOD) Activity	Assess changes in superoxide dismutase activity in serum, reported in units per milliliter (U/mL), using ELISA.	Baseline and 3 months of CPAP therapy.
Time with Oxygen Saturation Below 90% (T90%)	To measure the duration of time spent with oxygen saturation levels below 90% during sleep, reported as a percentage of total sleep time with SpO2 below 90%.	Baseline and 3 months of CPAP therapy.
Subjective Sleepiness	To assess changes in subjective sleepiness using the Epworth Sleepiness Scale (ESS), which is a self-administered questionnaire. The ESS measures the general level of daytime sleepiness, or average sleep propensity in daily activities, on a scale ranging from 0 to 24. A higher score on this scale indicates a greater likelihood of falling asleep in a variety of situations, suggesting worse daytime sleepiness.	Baseline and 3 months of CPAP therapy.

Collaborators and Investigators

• Sponsor: Nanjing Medical University

Publications and helpful links

General Publications

• Bortolotti M, Polito L, Battelli MG, Bolognesi A. Xanthine oxidoreductase: One enzyme for multiple physiological tasks. Redox Biol. 2021 May;41:101882. doi: 10.1016/j.redox.2021.101882. Epub 2021 Jan 27.
• Saugstad OD. Role of xanthine oxidase and its inhibitor in hypoxia: reoxygenation injury. Pediatrics. 1996 Jul;98(1):103-7.
• Ali MH, Schlidt SA, Chandel NS, Hynes KL, Schumacker PT, Gewertz BL. Endothelial permeability and IL-6 production during hypoxia: role of ROS in signal transduction. Am J Physiol. 1999 Nov;277(5):L1057-65. doi: 10.1152/ajplung.1999.277.5.L1057.
• Vickneson K, George J. Xanthine Oxidoreductase Inhibitors. Handb Exp Pharmacol. 2021;264:205-228. doi: 10.1007/164_2020_383.
• Nguyen NH, Tran GB, Nguyen CT. Anti-oxidative effects of superoxide dismutase 3 on inflammatory diseases. J Mol Med (Berl). 2020 Jan;98(1):59-69. doi: 10.1007/s00109-019-01845-2. Epub 2019 Nov 13.

Study record dates

Study Major Dates

• Study Start (Actual): July 1, 2024
• Primary Completion (Estimated): August 1, 2025
• Study Completion (Estimated): December 31, 2025

Study Registration Dates

• First Submitted: August 6, 2024
• First Submitted That Met QC Criteria: August 14, 2024
• First Posted (Actual): August 15, 2024

Study Record Updates

• Last Update Posted (Actual): August 16, 2024
• Last Update Submitted That Met QC Criteria: August 15, 2024
• Last Verified: August 1, 2024

More Information

Terms related to this study

• Keywords: Obstructive Sleep Apnea; CPAP treatment; Xanthine Oxidoreductase
• Additional Relevant MeSH Terms: Nervous System Diseases; Respiratory Tract Diseases; Respiration Disorders; Sleep Disorders, Intrinsic; Dyssomnias; Sleep Wake Disorders; Signs and Symptoms, Respiratory; Sleep Apnea Syndromes; Sleep Apnea, Obstructive; Apnea
• Other Study ID Numbers: 2024-SR-629

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO
• IPD Plan Description: The individual participant data will not be shared. The informed consent will be ansigned before enrolled in the study and ensured to keep personal information confidential.

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No