Obstructive Sleep Apnea and Telomere Length

Study Overview
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Brief Summary
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Obstructive sleep apnea (OSA) is a highly prevalent and morbid sleep disorder. Among the factors associated with its pathophysiology, the role of intermittent hypoxia stands out, contributing to the development of oxidative stress and inflammation. It is known that cumulative levels of these factors negatively influence the final portion of the DNA, known as telomere. In this sense, the investigators hypothesize that OSA is capable of accelerating aging process through telomere shortening mediated by inflammatory and oxidative markers. Thus, the aim of this study is to investigate the effect of OSA and its treatment with CPAP on the variation of telomere length and their associated mechanisms. For this, a randomized, double-blind, sham-controlled clinical study with 6 months duration will be conducted. We will recruit male participants with OSA diagnosis (apnea-hypopnea indexe15/hour), aged between 35-65 years and body mass index<35 kg/m2, which will be randomized to use CPAP or sham-CPAP for 6 months. Participants will visit the laboratory 7 times (baseline and after 1, 2, 3, 4, 5 and 6 months) and will be submitted to clinical and otorhinolaryngological evaluation, sleep questionnaires, polysomnography and blood collection for DNA and extraction and measurement of telomere length, as well as the expression of telomerase and oxidative and inflammatory markers (ADMA, homocysteine, cysteine, TBARS, 8-oxodG, TNF-a, IL-6 and IL-10). This project aims to contribute to the elucidation of the effect of OSA on telomere length maintenance, as well as the adjacent mechanisms to this relationship.

Official Title
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Study of the Effect of Obstructive Sleep Apnea on Telomere Length and Its Associated Mechanisms

Conditions
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Obstructive Sleep Apnea

Intervention / Treatment
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* Device: Continuous airway positive pressure


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: body mass index (BMI) of less than 35kg/m2 age between 35 and 65 years diagnosed by laboratory polysomnography with moderate to severe OSA (apnea-hypopnea index, AHI≥20 events/hour of sleep) Exclusion Criteria: illiteracy participants with more than 50% of the respiratory events obtained in the polysomnography exam being central apneas participants with central AHI>5 events/hour of sleep participants with sleepiness, measured by the Epworth sleepiness scale≥14 participants with severe otorhinolaryngological diseases that preclude the use of CPAP (severe nasal septum deviation, severe nasal turbinate hypertrophy, marked palatine and/or adenoid hypertrophy) abuse of alcohol or chronic use of psychoactive drugs participants with decompensated clinical, neurological or psychiatric illness participants with other sleep disorders; participants who had already undergone previous OSA treatments

Ages Eligible for Study
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Minimum Age: 35 Years
Maximum Age: 65 Years

Sexes Eligible for Study
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Male

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Double


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Continuous airway positive pressure<br>All participants in continuous airway positive pressure arm will use CPAP (model S10-Resmed®) with expiratory relief and nasal mask. | Device: Continuous airway positive pressure<br>* The continuous airway positive pressure will be used as the gold-standard treatment for obstructive sleep apnea for 6 months<br>|
| Sham Comparator: SHAM continuous airway positive pressure<br>Individuals in SHAM continuous airway positive pressure arm will use CPAP (model S7-Resmed®) with expiratory relief and nasal mask. The Sham-CPAP consists of a modified CPAP so that the pressure in the mask was less than 1 cm H2O. In this study, the Sham-CPAP equipment includes an increase in the expiratory orifice of the CPAP mask to eliminate airflow resistance, and a resistor with a small orifice was placed between the CPAP and the circuit. The noise produced by the ventilator and the airflow through the mask will be very similar to that of the effective CPAP. The diameter of the expiratory orifice was 10 cm H2O, and a 4 mm diameter resistor was placed between the trachea and the CPAP flow generator. | Device: Continuous airway positive pressure<br>* The continuous airway positive pressure will be used as the gold-standard treatment for obstructive sleep apnea for 6 months<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Change of Leukocyte telomere length from baseline to 6 months | It will be evaluated the change between leukocyte telomere length before and after the intervention | 6 months | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Change of sleep quality assessed by Pittsburgh Sleep Quality index from baseline to 6 months | It will be evaluated the change between sleep quality before and after the intervention | 6 months | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Sleep, Telomere, CPAP