The goal of this clinical trial is to learn whether aerobic exercise can improve sleep and nervous system regulation in adults with mild to moderate obstructive sleep apnea (OSA). The study will also examine whether exercise changes blood markers related to inflammation and brain health. The main questions this study aims to answer are: 1. Does four weeks of aerobic exercise change blood levels of irisin, brain-derived neurotrophic factor (BDNF), and markers related to inflammation? 2. Does aerobic exercise improve sleep apnea, heart rate variability, cognitive function, daytime sleepiness, sleep quality, and daily functioning? Researchers will compare an aerobic exercise group with a sleep education group to determine whether adding regular aerobic exercise provides additional benefits for people with mild to moderate OSA. Participants will be randomly assigned to one of two groups. Participants in the aerobic exercise group will: 1. Receive sleep education. 2. Complete four weeks of supervised treadmill exercise, three to five times per week. Each session will last about 45 to 60 minutes. Exercise intensity will be adjusted to each participant's heart rate and physical condition. Participants in the comparison group will: 1. Receive sleep education about OSA, common symptoms, treatment options, and healthy sleep habits. 2. Practice the recommended healthy sleep habits at home during the four-week study period. Participants in both groups will complete assessments before and after the four-week study period. These assessments will include an overnight sleep study, blood tests, heart rate measurements, cognitive tests, and questionnaires about daytime sleepiness, sleep quality, and daily functioning.
Obstructive sleep apnea (OSA) is a common chronic sleep-related breathing disorder characterized by repeated episodes of upper airway obstruction during sleep. These episodes can result in intermittent hypoxia, sleep fragmentation, oxidative stress, systemic inflammation, and autonomic nervous system imbalance. These physiological changes may also affect neuroplasticity, daytime functioning, and cognitive performance. Intermittent hypoxia associated with OSA may contribute to increased inflammatory activity and altered regulation of brain-derived neurotrophic factor (BDNF), which plays an important role in neuronal survival and neuroplasticity. Irisin, an exercise-related myokine, has been proposed to have anti-inflammatory and neuroprotective effects and may be involved in the regulation of BDNF. However, the effects of structured aerobic exercise on the relationship among irisin, BDNF, inflammatory responses, autonomic nervous system regulation, sleep, and cognitive function in individuals with OSA remain unclear. The purpose of this randomized controlled study is to investigate the effects of a four-week aerobic exercise intervention in adults with mild to moderate OSA. The study will examine whether aerobic exercise is associated with changes in circulating irisin, BDNF, inflammatory and anti-inflammatory markers, autonomic nervous system regulation, sleep-related outcomes, and cognitive function. A total of 50 participants will be randomly assigned to either an aerobic exercise group or a sleep education control group, with 25 participants in each group. Participants in both groups will complete assessments before the intervention and again after four weeks. Participants assigned to the aerobic exercise group will receive sleep education and participate in a supervised treadmill-based aerobic exercise program for four weeks. Exercise will be performed three to five times per week, with each session lasting approximately 45 to 60 minutes. Each exercise session will include a warm-up period, treadmill aerobic exercise, and a cool-down period. Exercise intensity will be individualized based on cardiopulmonary exercise testing (CPET)-derived parameters and will progressively increase over the four-week intervention period. Exercise sessions will be supervised by a physical therapist, and heart rate, blood pressure, oxygen saturation, and perceived exertion will be monitored to support exercise safety and individualized progression. Participants assigned to the control group will receive sleep education covering basic information about OSA, common symptoms, related sleep problems, commonly used treatments, and principles of healthy sleep. Participants will be encouraged to practice the recommended sleep hygiene strategies during the four-week study period. A physical therapist will contact participants during the intervention period to follow up on their participation and general condition. Assessments will be conducted before the intervention and after completion of the four-week intervention. These assessments will include polysomnography, cardiopulmonary exercise testing (CPET), blood sampling, heart rate variability analysis, cognitive testing, and sleep-related questionnaires. Blood samples will be collected to examine exercise-related changes in irisin and inflammatory and anti-inflammatory biomarkers. The study will also investigate the BDNF-related response to exercise as part of the proposed irisin-BDNF regulatory pathway. Heart rate variability will be assessed to evaluate autonomic nervous system regulation and sympathetic-parasympathetic balance. Cognitive assessments will evaluate domains including processing speed, attention, working memory, cognitive flexibility, and executive function. Sleep-related questionnaires will be used to assess daytime sleepiness and subjective sleep quality. Through the integration of physiological biomarkers, sleep measurements, autonomic nervous system assessment, and cognitive outcomes, this study aims to better understand the potential mechanisms through which aerobic exercise may benefit individuals with mild to moderate OSA. The findings may provide evidence for the potential role of exercise as a non-pharmacological adjunctive strategy for improving OSA-related physiological and neurocognitive dysfunction.
Study Type
INTERVENTIONAL
Allocation
RANDOMIZED
Purpose
TREATMENT
Masking
NONE
Enrollment
50
Participants will receive a 4-week supervised treadmill aerobic exercise program, performed 3-5 times per week for approximately 45-60 minutes per session. Exercise intensity will be individualized based on cardiopulmonary exercise testing (CPET)-derived parameters and progressively adjusted during the intervention. Each session will include warm-up, aerobic exercise, and cool-down periods.
Participants will receive a 20-30-minute sleep education session covering basic information about obstructive sleep apnea, common symptoms, treatment options, and sleep hygiene principles. Participants will be instructed to practice the recommended sleep hygiene strategies at home during the 4-week study period.
National Cheng Kung University Hospital
Tainan, Taiwan
Change in Apnea-Hypopnea Index (AHI)
Description: The apnea-hypopnea index will be obtained from the overnight Polysomnography (PSG) study. PSG will be performed in the sleep center of National Cheng Kung University Hospital. Less than 5 events/hour indicates normal; AHI between 5-14 events/hour indicates mild obstructive sleep apnea (OSA); AHI between 15-30 events/hour indicates moderate OSA; and AHI more than 30 events/hour indicates severe OSA.
Time frame: Baseline and Week 4
Change in Oxygen Desaturation Index (ODI)
The oxygen desaturation index (ODI) will be assessed using overnight polysomnography and will be used to evaluate changes in the frequency of nocturnal oxygen desaturation events following the intervention.
Time frame: Baseline and Week 4
Change in Irisin Level
Blood irisin levels will be measured before and after the intervention using an enzyme-linked immunosorbent assay to evaluate exercise-related changes in circulating irisin.
Time frame: Baseline and Week 4
Change in Brain-Derived Neurotrophic Factor (BDNF) Level
Blood BDNF levels will be measured before and after the intervention using an enzyme-linked immunosorbent assay to evaluate changes in BDNF associated with aerobic exercise.
Time frame: Baseline and Week 4
Change in Sleep Efficiency
Sleep efficiency will be assessed using overnight polysomnography and expressed as the percentage of total sleep time relative to time spent in bed. It will be used to evaluate changes in objective sleep quality following the 4-week intervention.
Time frame: Baseline and Week 4
Change in Arousal Index
The arousal index will be assessed using overnight polysomnography and expressed as the number of arousals per hour of sleep. It will be used to evaluate changes in sleep fragmentation following the intervention.
Time frame: Baseline and Week 4
Change in Blood Interleukin-6 (IL-6) Level
Blood interleukin-6 (IL-6) levels will be measured before and after the intervention using an enzyme-linked immunosorbent assay (ELISA). IL-6 will be used as a marker of systemic pro-inflammatory activity to evaluate whether aerobic exercise reduces inflammation in participants with obstructive sleep apnea.
Time frame: Baseline and Week 4
Change in Blood Interleukin-1 Beta (IL-1β) Level
Blood interleukin-1 beta (IL-1β) levels will be measured before and after the intervention using an enzyme-linked immunosorbent assay (ELISA). IL-1β will be used as a marker of systemic pro-inflammatory activity to evaluate changes in inflammatory response following aerobic exercise.
Time frame: Baseline and Week 4
Change in Blood Tumor Necrosis Factor-Alpha (TNF-α) Level
Blood tumor necrosis factor-alpha (TNF-α) levels will be measured before and after the intervention using an enzyme-linked immunosorbent assay (ELISA). TNF-α will be used as a marker of systemic pro-inflammatory activity to evaluate the effect of aerobic exercise on inflammation associated with obstructive sleep apnea.
Time frame: Baseline and Week 4
Change in Blood Interleukin-10 (IL-10) Level
Blood interleukin-10 (IL-10) levels will be measured before and after the intervention using an enzyme-linked immunosorbent assay (ELISA). IL-10 will be used as a marker of anti-inflammatory activity to evaluate changes in systemic inflammatory regulation following aerobic exercise.
Time frame: Baseline and Week 4
Change in Standard Deviation of Normal-to-Normal Intervals (SDNN)
SDNN will be derived from normal-to-normal R-R intervals obtained using a wearable ECG sensor and analyzed using Kubios HRV software. Data will be presented in milliseconds (ms). Higher SDNN values indicate greater overall heart rate variability.
Time frame: Baseline and Week 4
Change in Root Mean Square of Successive Differences (RMSSD)
RMSSD will be derived from normal-to-normal R-R intervals obtained using a wearable ECG sensor and analyzed using Kubios HRV software. Data will be presented in milliseconds (ms). Higher RMSSD values generally indicate greater parasympathetic cardiac modulation.
Time frame: Baseline and Week 4
Change in Low-Frequency to High-Frequency Power Ratio (LF/HF Ratio)
The LF/HF ratio will be calculated from frequency-domain heart rate variability analysis using Kubios HRV software. It will be used to evaluate changes in autonomic nervous system regulation and sympathetic-parasympathetic balance following the intervention.
Time frame: Baseline and Week 4
Change in Digit Symbol Substitution Test (DSST) Performance
The Digit Symbol Substitution Test will be used to assess processing speed, attention efficiency, and related cognitive performance. Participants will match symbols with corresponding numbers within 120 seconds. The raw score will be used for analysis, with higher scores indicating better performance.
Time frame: Baseline and Week 4
Change in Digit Span Test Performance
The Digit Span Test will be used to assess attention, short-term memory, and working memory. Forward and backward digit span performance will be evaluated before and after the intervention. Higher scores indicate better cognitive performance.
Time frame: Baseline and Week 4
Change in Stroop Color-Word Test Performance
The Stroop Color-Word Test will be used to assess attention, selective attention, inhibitory control, and executive function. Performance will be evaluated using completion time, errors, and interference-related performance as specified in the study protocol. Shorter completion time and fewer errors indicate better cognitive performance. Changes from baseline to Week 4 will be compared between groups.
Time frame: Baseline and Week 4
Change in Trail Making Test Performance
Performance will be evaluated using completion time for Parts A and B. Shorter completion time indicates better performance. Changes from baseline to Week 4 will be compared between groups.
Time frame: Baseline and Week 4
Change in Epworth Sleepiness Scale (ESS) Score
The Epworth Sleepiness Scale will be used to assess subjective daytime sleepiness. The scale consists of eight situations rated from 0 to 3, resulting in a total score ranging from 0 to 24. Higher scores indicate greater daytime sleepiness.
Time frame: Baseline and Week 4
Change in Pittsburgh Sleep Quality Index (PSQI) Score
The Pittsburgh Sleep Quality Index will be used to assess subjective sleep quality over the previous month. The questionnaire evaluates multiple components of sleep quality and produces a total score ranging from 0 to 21. Higher scores indicate poorer sleep quality.
Time frame: Baseline and Week 4
Change in Peak Oxygen Uptake (VO₂peak)
For cardiorespiratory fitness, peak oxygen uptake (VO₂peak) will be measured using cardiopulmonary exercise testing (CPET). Data will be presented in mL/kg/min. A higher value indicates better cardiorespiratory fitness and aerobic exercise capacity.
Time frame: Baseline and Week 4
Change in Oxygen Uptake at Anaerobic Threshold (VO₂ at AT)
For submaximal aerobic exercise capacity, oxygen uptake at the anaerobic threshold (VO₂ at AT) will be assessed using cardiopulmonary exercise testing (CPET). Data will be presented in mL/kg/min. A higher value indicates greater submaximal aerobic exercise capacity.
Time frame: Baseline and Week 4
Change in Work Rate at Anaerobic Threshold
Work rate at the anaerobic threshold will be assessed using cardiopulmonary exercise testing (CPET) performed on a cycle ergometer. Data will be presented in watts. A higher value indicates greater exercise capacity at the anaerobic threshold.
Time frame: Baseline and Week 4
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