Obstructive Sleep Apnea and Telomere Length

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

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.

Study Overview

• Status: Completed
• Conditions: Obstructive Sleep Apnea
• Intervention / Treatment: Device: Continuous airway positive pressure

• Study Type: Interventional
• Enrollment (Actual): 46
• Phase: Phase 2

Contacts and Locations

Study Locations

• Brazil
  • São Paulo, Brazil
    • Universidade Federal de Sao Paulo

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 35 years to 65 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No

Description

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

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Double

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Continuous airway positive pressure; 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; The continuous airway positive pressure will be used as the gold-standard treatment for obstructive sleep apnea for 6 months
Sham Comparator: SHAM continuous airway positive pressure; 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; The continuous airway positive pressure will be used as the gold-standard treatment for obstructive sleep apnea for 6 months

What is the study measuring?

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

Other Outcome Measures

Outcome Measure	Measure Description	Time Frame
Change of depressive symptoms assessed by Beck depression inventory from baseline to 6 months	It will be evaluated the change between depressive symptoms before and after the intervention	6 months
Change of body mass index from baseline to 6 months	It will be evaluated the change between body mass index before and after the intervention	6 months
Change of anxiety symptoms assessed by Anxiety status scale from baseline to 6 months	It will be evaluated the change between anxiety symptoms before and after the intervention	6 months
Change of cervical circumference from baseline to 6 months	It will be evaluated the change between cervical circumference before and after the intervention	6 months
Change of abdominal circumference from baseline to 6 months	It will be evaluated the change between abdominal circumference before and after the intervention	6 months

Collaborators and Investigators

• Sponsor: Associação Fundo de Incentivo à Pesquisa

Study record dates

Study Major Dates

• Study Start (Actual): July 5, 2018
• Primary Completion (Actual): June 11, 2021
• Study Completion (Actual): April 30, 2022

Study Registration Dates

• First Submitted: April 26, 2021
• First Submitted That Met QC Criteria: April 29, 2021
• First Posted (Actual): May 5, 2021

Study Record Updates

• Last Update Posted (Actual): May 8, 2023
• Last Update Submitted That Met QC Criteria: May 5, 2023
• Last Verified: May 1, 2023

More Information

Terms related to this study

• Keywords: Sleep; CPAP; Telomere
• 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: 0232/2018

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No
• product manufactured in and exported from the U.S.: No