Role of Sleep in Cardiovascular Functions

Study Overview
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Brief Summary
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Sleep and particularly deep sleep are playing an important role for brain and body health. Poor sleep has been associated with risk factors for cardiovascular disease and moreover, is hypothesized to increased mortality risk of cardiovascular diseases. Yet, the role of specific sleep processes for cardiovascular function remains unclear. Particularly deep sleep, which is manifested by large amplitude, low frequency oscillations is of importance for the restorative functions of sleep. Thus, the modulation of deep sleep by auditory stimulation will be of central interests to assess the cause-effect relationship of specific processes within sleep for cardiovascular regulation. This study will assess the effects of slow wave modulating auditory stimulation on cardiovasuclar functions in healthy male participants.

Official Title
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Modulation of Sleep Slow Wave Activity Through Acoustic Stimulation and Its Consequences on Cardiovascular Functions

Conditions
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Sleep

Intervention / Treatment
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* Other: Acoustic stimulation
* Other: SHAM acoustic stimulation


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Informed Consent Good general health status Male subjects 18-84 years of age Native German speaker or good understanding of German Exclusion Criteria: Contraindications on ethical grounds, Known or suspected non-compliance, drug or alcohol abuse, Regular medication intake that could pronouncedly affect outcomes of interest (e.g. beta-blocker) Long (> 9.5 hours per night) or short sleepers (< 6.5 hours per night), Smoking (regular smoker, >10 days per year, smoking not allowed during study participation) Participation in another study with investigational drug/therapy/interventions within the 30 days preceding and during the present study (start date adapted accordingly), Diseases or lesions of the nervous system (acute or residual included neurological and psychiatric diseases), Clinically significant concomitant disease states (e.g., renal failure, hepatic dysfunction, cardiovascular disease, etc.), Pacemaker, Intake of on-label sleep medication, Presence or suspicion of sleep disorders (e.g., insomnia, sleep disordered breathing (apnea), restless legs syndrome). Possibility of apnea might be assessed in the screening night, Body Mass Index < 18 or > 30 kg/m2, Irregular sleep-wake rhythm (e.g. shift working), Bad sleep quality during screening night (e.g. < 75% sleep efficiency in screening night) Significant sleep complaints in general or excessive daytime sleepiness (PSQI > 5; ESS ≥ 11), Travelling more than 2 time zones in the 2 weeks before experimental session starts or during intervention (start of experiment will be adapted to fit with this criteria), Hearing disability/ hearing aid (only an exclusion if in a simple audiometry participants cannot hear intervention tone sound levels), Skin disorders/problems/allergies (face region) that will significantly worsen with electrode application, High caffeine consumption (> 5 servings/day; including coffee and caffeinated energy drinks),

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 84 Years

Sexes Eligible for Study
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Male

Accepts Healthy Volunteers
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Accepts Healthy Volunteers

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Basic Science
Allocation: Randomized
Intervention Model: Crossover Assignment
Interventional Model Description: we forecast the enrollment of 70 participants which includes the conduction of pilot assessments and the collection of 18 complete participant datasets for the main clinical trial (described here).
Masking: Double


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Active Comparator: Slow waves enhancing acoustic stimulation<br>During non-rapid eye movement (NREM) sleep, acoustic stimuli will be played to increase slow wave amplitude. | Other: Acoustic stimulation<br>* Acoustic stimulation to modulate slow waves.<br>|
| Sham Comparator: SHAM: no application of acoustic stimuli<br>During NREM sleep no acoustic stimuli will be played. | Other: SHAM acoustic stimulation<br>* This is the sham-control intervention; only the biosignal will be recorded but no acoustic stimulation will be played.<br>|
| Active Comparator: Slow waves decreasing acoustic stimulation<br>During NREM sleep acoustic stimuli will be played to decrease/modulate slow waves amplitude in a dose-dependent way (e.g. less pronounced than arm 1). | Other: Acoustic stimulation<br>* Acoustic stimulation to modulate slow waves.<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Cardiac autonomic regulation | assessed by heart rate variability derived from electrocardiography | continuously across approximately 8 hours of sleep with and without acoustic stimulation | 
| Change in cardiac autonomic regulation | assessed by changes in heart rate variability derived from electrocardiography | Before to after approximately 8 hours of sleep with and without acoustic stimulation | 
| Heart rate | measured with electrocardiography | continuously across approximately 8 hours of sleep with and without acoustic stimulation | 
| Change in heart rate | measured with electrocardiography | Before to after approximately 8 hours of sleep with and without acoustic stimulation | 
| Marker for sleep depth | Slow wave activity assessed with high-density electroencephalography(hdEEG) | continuously across approximately 8 hours of sleep with and without acoustic stimulation | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Change in vascular functioning | Assessed by outcomes of blood profiles of vascular inflammation, pulmonal arterial pressure, intima media thickness, or echocardiography | Before and/or after approximately 8 hours of sleep with and without acoustic stimulation | 
| Arterial pressure waveform | assessed by arterial pressure waveform measures | continuously across approximately 8 hours of sleep with and without acoustic stimulation | 
| Change in arterial pressure waveform | assessed by arterial pressure waveform measures | Before to after approximately 8 hours of sleep with and without acoustic stimulation | 
| Oxyen saturation | assessed by pulse oximetry | continuously across approximately 8 hours of sleep with and without acoustic stimulation | 
| Overnight memory consolidation | Assessed by memory tasks | Before to after approximately 8 hours of sleep with and without acoustic stimulation | 
| Changes in vigilance | assessed by simple vigilance task | Before to after approximately 8 hours of sleep with and without acoustic stimulation | 
| Changes in muscular fatigue | assessed by simple muscular fatigue task | Before to after approximately 8 hours of sleep with and without acoustic stimulation | 
| Changes in bandwidth of of 0.5-30 Hz of high-density electroencephalography (hdEEG) | Assessment of resting state and task-related hdEEG | Before to after approximately 8 hours of sleep with and without acoustic stimulation | 
| Hypnogram | assessed by sleep staging of hdEEG data | Over approximately 8 hours of sleep with and without acoustic stimulation |