Role of Sleep in Cardiovascular Functions

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

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.

Study Overview

• Status: Active, not recruiting
• Conditions: Sleep
• Intervention / Treatment: Other: Acoustic stimulation; Other: SHAM acoustic stimulation

• Study Type: Interventional
• Enrollment (Anticipated): 70
• Phase: Not Applicable

Contacts and Locations

Study Locations

• Switzerland
  • Schweiz
    • Zurich, Schweiz, Switzerland, 8057
      • ETH Zurich

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 16 years to 82 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: Male

Description

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),

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Basic Science
• Allocation: Randomized
• Interventional Model: Crossover Assignment
• Masking: Double

Number of Arms

3

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Active Comparator: Slow waves enhancing acoustic stimulation; During non-rapid eye movement (NREM) sleep, acoustic stimuli will be played to increase slow wave amplitude.	Other: Acoustic stimulation; Acoustic stimulation to modulate slow waves.
Sham Comparator: SHAM: no application of acoustic stimuli; During NREM sleep no acoustic stimuli will be played.	Other: SHAM acoustic stimulation; This is the sham-control intervention; only the biosignal will be recorded but no acoustic stimulation will be played.
Active Comparator: Slow waves decreasing acoustic stimulation; 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; Acoustic stimulation to modulate slow waves.

What is the study measuring?

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

Other Outcome Measures

Outcome Measure	Measure Description	Time Frame
Incidence of Intervention-related Adverse Events (Safety and Tolerability)	Any adverse or serious adverse event during the study period will be assessed	Through study completion approximately one month
Chronotype	Assessment of circadian type	During initial screening session before start of experimental period (single-time assessment during one initial 1-day visit)
Body mass index	Assessment of height, weight to calculate body mass index	During initial screening session before start of experimental period (single-time assessment during one initial 1-day visit)
Hip-to-waist ratio	Assessment of hip and waist circumference to calculate hip-to-waist ratio	During initial screening session before start of experimental period (single-time assessment during one initial 1-day visit)
Subjective sleep quality	assessed by Pittsburgh Sleep quality index	During initial screening session before start of experimental period (single-time assessment during one initial 1-day visit)
Daytime sleepiness	assessed by Epworth sleepiness scale	During initial screening session before start of experimental period (single-time assessment during one initial 1-day visit)
Change in sleepiness	assessed by Karolinska Sleepiness Scale or Stanford Sleepiness Scale	Before to after approximately 8 hours of sleep with and without acoustic stimulation
Body composition	Assessment of body composition through DEXA scan	During initial screening session before start of experimental period (single-time assessment during one initial 1-day visit)

Collaborators and Investigators

• Sponsor: Caroline Lustenberger
• Investigators: Principal Investigator: Caroline Lustenberger, PhD, ETH Zurich

Study record dates

Study Major Dates

• Study Start (Actual): January 13, 2020
• Primary Completion (Anticipated): October 1, 2023
• Study Completion (Anticipated): October 1, 2023

Study Registration Dates

• First Submitted: October 18, 2019
• First Submitted That Met QC Criteria: November 14, 2019
• First Posted (Actual): November 18, 2019

Study Record Updates

• Last Update Posted (Actual): November 18, 2022
• Last Update Submitted That Met QC Criteria: November 15, 2022
• Last Verified: November 1, 2022

More Information

Terms related to this study

• Other Study ID Numbers: 2019-01538

Drug and device information, study documents

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