Metabolic and Cognitive Consequences of Noise-induced Sleep Disturbance

Sleep Disturbance Clinical Trial

Official title:

Metabolic and Cognitive Consequences of Noise-induced Sleep Disturbance

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT05319262
• Other study ID #: 234826201
• Status: Completed
• Phase: N/A
• Start date: April 24, 2022
• Est. completion date: June 3, 2022

Study information

• Verified date: June 2022
• Source: Göteborg University
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

This study will investigate the biological mechanisms linking sleep disruption by noise and the development of disease. In a laboratory sleep study, we will play traffic sounds of different types (road, rail and air) and noise levels during the night. We will also have nights with sound from so-called "white noise machines". These generate a low-level and continuous noise that may improve sleep by "masking" the traffic noises that would otherwise disturb sleep. We will also measure objective sleep quality and quantity, cognitive performance across multiple domains, self-reported sleep and wellbeing outcomes, and blood samples. Blood samples will be analysed to identify metabolic changes in different nights. Identifying biomarkers that are impacted by sleep fragmentation will establish the currently unclear pathways by which chronic noise exposure at night can lead to the development of diseases in the long term, especially cardiometabolic disorders.

Description:

The experimental sleep study has the overarching goal of deepening our understanding of experimentally-induced disruption of sleep and changes in metabolic and cognitive function, and to determine the efficacy of a potential non-pharmacological intervention to promote sleep. To this end, the study will address the following independent aims:

Aim 1: Determine associations between novel physiologic markers of sleep and metabolic and cognitive function. We will measure the sleep of healthy volunteers using novel and classical indictors of sleep architecture. Each morning we will obtain blood samples for metabolomics analysis and administer a neurocognitive test battery.

Aim 2: Determine the biological and neurobehavioral consequences of noise-disrupted sleep. We will compare effects on sleep, metabolomics and cognitive function between quiet nights and nights with traffic noise.

Aim 3: Evaluate the effects of continuous pink noise throughout the night. Sub-aim 1: To determine if continuous noise (pink noise) per se improves or disturbs sleep, we will investigate changes in novel and classical indictors of sleep architecture and disturbance induced by pink noise relative to quiet baseline nights. Sub-aim 2: To determine if pink noise reduces sleep disturbance by traffic noise, we will investigate changes in sleep fragmentation and continuity, and cortical and autonomic arousal, from nights with both traffic noise and pink noise compared to nights with traffic noise only.

The study will be conducted at in the University of Gothenburg sound environment laboratory (SEL). The SEL is a high fidelity research laboratory equipped to simulate a typical apartment, including three individually light-, sound- and vibration-isolated private bedrooms. Ceiling mounted speakers in each room allow us to create a realistic acoustic environment by transmitting sound exposures from the control room to each bedroom individually.

This study has a prospective within-subjects cross-over design. Participants (N=12) will each spend five consecutive nights in the SEL with a sleep opportunity between 23:00-07:00. Daytime sleep will be prohibited, confirmed with measures of daytime activity via wrist actigraphy monitors worn continuously throughout the study. Three subjects will take part concurrently, in separate bedrooms. The first night is a habituation period to the study protocol and for familiarisation with the test procedures. Study nights 2-5 are the experimental nights and will be randomly assigned across participants using a Latin square design to avoid first-order carryover effects. Each subject will be exposed to one night of each of the following:

Quiet night: No noise will be played, serving as a control night to assess individual baseline sleep, metabolic profile, and cognitive performance; Traffic noise night to determine consequences of noise-disrupted sleep; Pink noise night: To determine impact of continuous pink noise on sleep; Traffic + pink noise night: simultaneous traffic and pink noise at the same sound pressure levels as in the traffic-only and pink noise-only nights, to determine sleep-protecting effects of pink noise in the face of traffic noise.

Each night we will record physiologic sleep with polysomnography (PSG) and cardiac activity with electrocardiography (ECG). Each study morning, subjects will provide a 2ml blood sample, complete cognitive testing and answer questionnaires and will depart the SEL to follow their normal daytime routine. They will return to the SEL at 20:00 each evening to prepare for sleep measurements. Caffeine will be prohibited after 15:00 and alcohol will be prohibited at all times. Because sound-induced auditory fatigue may be affected by noise exposure during participant's normal routines,60 they will wear a noise dosimeter during the week of the study to record their daytime noise exposure. Because extreme and/or variable dietary behaviour can affect the metabolome/lipoprotein profile, participants will be given guidance that they should eat a similar evening meal on each day of the laboratory study, confirmed with a food diary, The actual meal itself can be different for different study participants, because the study has a within-subjects design.

Sleep will be recorded with ambulatory polysomnography (PSG) and cardiac activity with electrocardiography (ECG) and finger pulse photoplethysmogram. Data are recorded offline onto the sleep recorder, and will be downloaded and checked every study morning to ensure data quality. In addition to traditional sleep analysis performed by the research group at the University of Gothenburg, raw PSG data will be used to calculate the Odds Ratio Project, a novel metric of sleep depth and stability.

Each study morning subjects will provide a 2 ml blood sample for plasma metabolomics analysis. To ensure reliable data, blood samples will be taken at the same time every day to mitigate circadian effects, before eating or drinking anything except water, and each sample will be handled in the same way i.e. centrifuged, aliquoted and stored in -80C freezers. Subjects will eat the same food each study evening to mitigate within-subject dietary effects on the blood metabolome.

Each morning, subjects will complete a computerised cognitive test battery taking approximately 20 minutes, that includes 10 tests across a range of cognitive domains (motor praxis, visual object learning, fractal 2-back, abstract matching, line orientation, emotion recognition, matrix reasoning, digit symbol substitution, balloon analog risk, psychomotor vigilance). Cognition data will be analysed to determine key measures of cognitive speed and accuracy, adjusting for practice effects and the difficulty of the stimulus set.

Subjects will complete a battery of one-time validated questionnaires to measure their general health (SF-36), chronotype, noise sensitivity, habitual sleep quality, environmental sensitivity, and annoyance and sleep disturbance by noise. Subjects will also answer a questionnaire each study evening and morning, involving questions on sleepiness (Karolinska Sleepiness Scale), auditory fatigue, sleep disturbance by noise, and validated sleep and disturbance questions.

Subjects will wear a noise dosimeter during the week of the study to record their daytime noise exposure (sound pressure level only, no actual sound recordings).

Participants will wear a wrist actigraphy monitor continuously throughout the study period, and also for the week before the study, to confirm habitual sleep-wake times and to measure physical activity levels.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 12
• Est. completion date: June 3, 2022
• Est. primary completion date: June 3, 2022
• Accepts healthy volunteers: Accepts Healthy Volunteers
• Gender: All
• Age group: 18 Years to 30 Years

Eligibility

Inclusion Criteria:

1) live in or around the city of Gothenburg area (Sweden)

Exclusion Criteria:

1. aged <18 or >30 years;

2. habitual sleep and wake timings more than ±1 hour different from the study sleep times (i.e. habitual sleep time should be 22:00-00:00 and habitual wake time should be 06:00-08:00);

3. BMI>25 kg/m2;

4. regular sleep medication use (prescribed or "over-the-counter");

5. poor hearing acuity (measured during screening via pure tone audiometry);

6. diagnosed with sleep disorders;

7. indications of sleep apnea on the STOP-BANG questionnaire;

8. shift work;

9. smoking, vaping, snus, or other nicotine use;

10. pre-existing use of "white noise machines" as a sleep aid.

Related Conditions & MeSH terms

• Cognitive Change
• Dyssomnias
• Metabolic Disturbance
• Noise Exposure
• Parasomnias
• Sleep Disturbance
• Sleep Hygiene

Intervention

Radiation:
• Pink noise exposure
Continuous pink noise sound exposure at 45 dBA, throughout the whole night
• Traffic noise
120 traffic noise events (40 each of road, rail and aircraft), introduced at maximum sound pressure levels ranging between 45-65 dB LAS.max.

Locations

Country	Name	City	State
Sweden	University of Gothenburg	Gothenburg	Västra Götaland

Sponsors (3)

Lead Sponsor	Collaborator
Göteborg University	University of Manitoba, University of Pennsylvania

Country where clinical trial is conducted

Sweden, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Metabolomics and lipids	Concentrations of 41 metabolites, including amino acids, amines, alcohols, carboxylic acids, choline, keto acids, sugars, and sulfones. Lipoprotein profile, including concentrations of triglycerides, cholesterol, phospholipids, and apolipoproteins.	On each of the five study mornings
Primary	Baseline total sleep time	Measured via polysomnography/EEG, scored according to American Academy of Sleep Medicine guidelines	During the Control night
Primary	Total sleep time during exposure to nocturnal traffic	Measured via polysomnography/EEG, scored according to American Academy of Sleep Medicine guidelines	During the traffic noise night
Primary	Total sleep time during exposure to pink noise	Measured via polysomnography/EEG, scored according to American Academy of Sleep Medicine guidelines	During the pink noise night
Primary	Total sleep time during exposure to traffic noise + pink noise	Measured via polysomnography/EEG, scored according to American Academy of Sleep Medicine guidelines	During the Traffic noise + pink noise night
Primary	Total amount of baseline N1 sleep	Measured via polysomnography/EEG, scored according to American Academy of Sleep Medicine guidelines	During the Control night
Primary	Total amount of baseline N2 sleep	Measured via polysomnography/EEG, scored according to American Academy of Sleep Medicine guidelines	During the Control night
Primary	Total amount of baseline N3 sleep	Measured via polysomnography/EEG, scored according to American Academy of Sleep Medicine guidelines	During the Control night
Primary	Total amount of baseline rapid eye movement (REM) sleep	Measured via polysomnography/EEG, scored according to American Academy of Sleep Medicine guidelines	During the Control night
Primary	Total amount of N1 sleep during exposure to nocturnal traffic	Measured via polysomnography/EEG, scored according to American Academy of Sleep Medicine guidelines	During the traffic noise night
Primary	Total amount of N2 sleep during exposure to nocturnal traffic	Measured via polysomnography/EEG, scored according to American Academy of Sleep Medicine guidelines	During the traffic noise night
Primary	Total amount of N3 sleep during exposure to nocturnal traffic	Measured via polysomnography/EEG, scored according to American Academy of Sleep Medicine guidelines	During the traffic noise night
Primary	Total amount of rapid eye movement (REM) sleep during exposure to nocturnal traffic	Measured via polysomnography/EEG, scored according to American Academy of Sleep Medicine guidelines	During the traffic noise night
Primary	Total amount of N1 sleep during exposure to pink noise	Measured via polysomnography/EEG, scored according to American Academy of Sleep Medicine guidelines	During the pink noise night
Primary	Total amount of N2 sleep during exposure to pink noise	Measured via polysomnography/EEG, scored according to American Academy of Sleep Medicine guidelines	During the pink noise night
Primary	Total amount of N3 sleep during exposure to pink noise	Measured via polysomnography/EEG, scored according to American Academy of Sleep Medicine guidelines	During the pink noise night
Primary	Total amount of rapid eye movement (REM) sleep during exposure to pink noise	Measured via polysomnography/EEG, scored according to American Academy of Sleep Medicine guidelines	During the pink noise night
Primary	Total amount of N1 sleep during exposure to traffic noise + pink noise	Measured via polysomnography/EEG, scored according to American Academy of Sleep Medicine guidelines	During the Traffic noise + pink noise night
Primary	Total amount of N2 sleep during exposure to traffic noise + pink noise	Measured via polysomnography/EEG, scored according to American Academy of Sleep Medicine guidelines	During the Traffic noise + pink noise night
Primary	Total amount of N3 sleep during exposure to traffic noise + pink noise	Measured via polysomnography/EEG, scored according to American Academy of Sleep Medicine guidelines	During the Traffic noise + pink noise night
Primary	Total amount of rapid eye movement (REM) sleep during exposure to traffic noise + pink noise	Measured via polysomnography/EEG, scored according to American Academy of Sleep Medicine guidelines	During the Traffic noise + pink noise night
Primary	Baseline wakefulness after sleep onset (WASO)	Total number of minutes awake during the night after the first appearance of sleep of any stage. Measured via polysomnography/EEG, scored according to American Academy of Sleep Medicine guidelines	During the Control night
Primary	Wakefulness after sleep onset (WASO) during exposure to nocturnal traffic	Total number of minutes awake during the night after the first appearance of sleep of any stage. Measured via polysomnography/EEG, scored according to American Academy of Sleep Medicine guidelines	During the Traffic noise night
Primary	Wakefulness after sleep onset (WASO) during exposure to pink noise	Total number of minutes awake during the night after the first appearance of sleep of any stage. Measured via polysomnography/EEG, scored according to American Academy of Sleep Medicine guidelines	During the Pink noise night
Primary	Wakefulness after sleep onset (WASO) during exposure to traffic noise + pink noise	Total number of minutes awake during the night after the first appearance of sleep of any stage. Measured via polysomnography/EEG, scored according to American Academy of Sleep Medicine guidelines	During the Traffic noise + pink noise night
Primary	Baseline number of awakenings	Measured via polysomnography/EEG, scored according to American Academy of Sleep Medicine guidelines	During the Control night
Primary	Number of awakenings during exposure to nocturnal traffic	Measured via polysomnography/EEG, scored according to American Academy of Sleep Medicine guidelines	During the Traffic noise night
Primary	Number of awakenings during exposure to pink noise	Measured via polysomnography/EEG, scored according to American Academy of Sleep Medicine guidelines	During the Pink noise night
Primary	Number of awakenings during exposure to traffic noise + pink noise	Measured via polysomnography/EEG, scored according to American Academy of Sleep Medicine guidelines	During the Traffic noise + pink noise night
Primary	Baseline sleep onset latency (SOL)	Defined as the time from lights out to the first epoch of sleep measured via polysomnography/EEG, scored according to American Academy of Sleep Medicine guidelines.	During the Control night
Primary	Sleep onset latency (SOL) during exposure to nocturnal traffic	Defined as the time from lights out to the first epoch of sleep measured via polysomnography/EEG, scored according to American Academy of Sleep Medicine guidelines.	During the Traffic noise night
Primary	Sleep onset latency (SOL) during exposure to pink noise	Defined as the time from lights out to the first epoch of sleep measured via polysomnography/EEG, scored according to American Academy of Sleep Medicine guidelines.	During the Pink noise night
Primary	Sleep onset latency (SOL) during exposure to nocturnal traffic and pink noise	Defined as the time from lights out to the first epoch of sleep measured via polysomnography/EEG, scored according to American Academy of Sleep Medicine guidelines.	During the Traffic noise + Pink noise night
Primary	Baseline sleep efficiency	Defined as the percentage of time in bed spent in a non-wake sleep stage, measured via polysomnography/EEG, scored according to American Academy of Sleep Medicine guidelines.	During the Control night
Primary	Sleep efficiency during exposure to nocturnal traffic	Defined as the percentage of time in bed spent in a non-wake sleep stage, measured via polysomnography/EEG, scored according to American Academy of Sleep Medicine guidelines.	During the Traffic noise night
Primary	Sleep efficiency during exposure to pink noise	Defined as the percentage of time in bed spent in a non-wake sleep stage, measured via polysomnography/EEG, scored according to American Academy of Sleep Medicine guidelines.	During the Pink noise night
Primary	Sleep efficiency during exposure to nocturnal traffic and pink noise	Defined as the percentage of time in bed spent in a non-wake sleep stage, measured via polysomnography/EEG, scored according to American Academy of Sleep Medicine guidelines.	During the Traffic noise + pink noise night
Primary	Baseline sleep depth assessed using the odds ratio product (ORP)	Average ORP over the full night, from 0 (never occurs during wake) to 2.5 (only occurs during wake). Derived via polysomnography/EEG measurements.	During the Control night
Primary	Sleep depth assessed using the odds ratio product (ORP) during exposure to nocturnal traffic	Average ORP over the full night, from 0 (never occurs during wake) to 2.5 (only occurs during wake). Derived via polysomnography/EEG measurements.	During the Traffic noise night
Primary	Sleep depth assessed using the odds ratio product (ORP) during exposure to pink noise	Average ORP over the full night, from 0 (never occurs during wake) to 2.5 (only occurs during wake). Derived via polysomnography/EEG measurements.	During the Pink noise night
Primary	Sleep depth assessed using the odds ratio product (ORP) during exposure to traffic noise and pink noise	Average ORP over the full night, from 0 (never occurs during wake) to 2.5 (only occurs during wake). Derived via polysomnography/EEG measurements.	During the Traffic noise + pink noise night
Primary	Spontaneous maximal change of odds ratio product (ORP)	Primary measure of acute sleep disruption by noise, calculated as the difference between the ORP in the 30s prior to noise onset and the maximum ORP during traffic noise. Averaged over 120 sham noise events during the night.	During the Control night
Primary	Maximal change of odds ratio product (ORP) during exposure to traffic noise events	Primary measure of acute sleep disruption by noise, calculated as the difference between the ORP in the 30s prior to noise onset and the maximum ORP during traffic noise. Averaged over all 120 noise events during the night.	During the Traffic noise night
Primary	Maximal change of odds ratio product (ORP) during exposure to traffic noise events	Primary measure of acute sleep disruption by noise, calculated as the difference between the ORP in the 30s prior to noise onset and the maximum ORP during traffic noise. Averaged over all 120 noise events during the night.	During the Traffic noise + pink noise night
Primary	Spontaneous change of odds ratio product (ORP) during exposure to pink noise	Primary measure of acute sleep disruption by noise, calculated as the difference between the ORP in the 30s prior to noise onset and the maximum ORP during traffic noise. Averaged over 120 sham noise events during the night.	During the Pink noise night
Primary	Baseline morning neurobehavioural speed	Average of one key speed indicator from each of 10 cognitive tests (motor praxis, visual object learning, fractal 2-back, abstract matching, line orientation, emotion recognition, matrix reasoning, digit symbol substitution, balloon analog risk, psychomotor vigilance)	In the morning immediately after the Control night
Primary	Morning neurobehavioural speed after exposure to nocturnal traffic	Average of one key speed indicator from each of 10 cognitive tests (motor praxis, visual object learning, fractal 2-back, abstract matching, line orientation, emotion recognition, matrix reasoning, digit symbol substitution, balloon analog risk, psychomotor vigilance)	In the morning immediately after the Traffic noise night
Primary	Morning neurobehavioural speed after exposure to pink noise	Average of one key speed indicator from each of 10 cognitive tests (motor praxis, visual object learning, fractal 2-back, abstract matching, line orientation, emotion recognition, matrix reasoning, digit symbol substitution, balloon analog risk, psychomotor vigilance)	In the morning immediately after the Pink noise night
Primary	Morning neurobehavioural speed after exposure to nocturnal traffic and pink noise	Average of one key speed indicator from each of 10 cognitive tests (motor praxis, visual object learning, fractal 2-back, abstract matching, line orientation, emotion recognition, matrix reasoning, digit symbol substitution, balloon analog risk, psychomotor vigilance)	In the morning immediately after the Traffic noise + pink noise night
Primary	Baseline morning neurobehavioural accuracy	Average of one key accuracy indicator from each of 9 cognitive tests (motor praxis, visual object learning, fractal 2-back, abstract matching, line orientation, emotion recognition, matrix reasoning, digit symbol substitution, psychomotor vigilance)	In the morning immediately after the Control night
Primary	Morning neurobehavioural accuracy after exposure to nocturnal traffic	Average of one key accuracy indicator from each of 9 cognitive tests (motor praxis, visual object learning, fractal 2-back, abstract matching, line orientation, emotion recognition, matrix reasoning, digit symbol substitution, psychomotor vigilance)	In the morning immediately after the Traffic noise night
Primary	Morning neurobehavioural accuracy after exposure to pink noise	Average of one key accuracy indicator from each of 9 cognitive tests (motor praxis, visual object learning, fractal 2-back, abstract matching, line orientation, emotion recognition, matrix reasoning, digit symbol substitution, psychomotor vigilance)	In the morning immediately after the Pink noise night
Primary	Morning neurobehavioural accuracy after exposure to nocturnal traffic and pink noise	Average of one key accuracy indicator from each of 9 cognitive tests (motor praxis, visual object learning, fractal 2-back, abstract matching, line orientation, emotion recognition, matrix reasoning, digit symbol substitution, psychomotor vigilance)	In the morning immediately after the Traffic noise + pink noise night
Primary	Baseline evening neurobehavioural speed	Average of one key speed indicator from each of 10 cognitive tests (motor praxis, visual object learning, fractal 2-back, abstract matching, line orientation, emotion recognition, matrix reasoning, digit symbol substitution, balloon analog risk, psychomotor vigilance)	In the evening of the day following the Control night
Primary	Evening neurobehavioural speed after exposure to nocturnal traffic	Average of one key speed indicator from each of 10 cognitive tests (motor praxis, visual object learning, fractal 2-back, abstract matching, line orientation, emotion recognition, matrix reasoning, digit symbol substitution, balloon analog risk, psychomotor vigilance)	In the evening of the day following the Traffic noise night
Primary	Evening neurobehavioural speed after exposure to pink noise	Average of one key speed indicator from each of 10 cognitive tests (motor praxis, visual object learning, fractal 2-back, abstract matching, line orientation, emotion recognition, matrix reasoning, digit symbol substitution, balloon analog risk, psychomotor vigilance)	In the evening of the day following the Pink noise night
Primary	Evening neurobehavioural speed after exposure to nocturnal traffic and pink noise	Average of one key speed indicator from each of 10 cognitive tests (motor praxis, visual object learning, fractal 2-back, abstract matching, line orientation, emotion recognition, matrix reasoning, digit symbol substitution, balloon analog risk, psychomotor vigilance)	In the evening of the day following the Traffic noise + pink noise night
Primary	Baseline evening neurobehavioural accuracy	Average of one key speed indicator from each of 9 cognitive tests (motor praxis, visual object learning, fractal 2-back, abstract matching, line orientation, emotion recognition, matrix reasoning, digit symbol substitution, psychomotor vigilance)	In the evening of the day following the Control night
Primary	Evening neurobehavioural accuracy after exposure to nocturnal traffic	Average of one key speed indicator from each of 9 cognitive tests (motor praxis, visual object learning, fractal 2-back, abstract matching, line orientation, emotion recognition, matrix reasoning, digit symbol substitution, psychomotor vigilance)	In the evening of the day following the Traffic noise night
Primary	Evening neurobehavioural accuracy after exposure to pink noise	Average of one key speed indicator from each of 9 cognitive tests (motor praxis, visual object learning, fractal 2-back, abstract matching, line orientation, emotion recognition, matrix reasoning, digit symbol substitution, psychomotor vigilance)	In the evening of the day following the Pink noise night
Primary	Evening neurobehavioural accuracy after exposure to nocturnal traffic and pink noise	Average of one key speed indicator from each of 9 cognitive tests (motor praxis, visual object learning, fractal 2-back, abstract matching, line orientation, emotion recognition, matrix reasoning, digit symbol substitution, psychomotor vigilance)	In the evening of the day following the Traffic noise + pink noise night
Primary	Baseline Ethanol concentration (mmol/L)	Determined from NMR analysis of blood plasma	In the morning immediately after the Control night
Primary	Baseline Trimethylamine-N-oxide concentration (mmol/L)	Determined from NMR analysis of blood plasma	In the morning immediately after the Control night
Primary	Baseline 2-Aminobutyric acid concentration (mmol/L)	Determined from NMR analysis of blood plasma	In the morning immediately after the Control night
Primary	Baseline Alanine concentration (mmol/L)	Determined from NMR analysis of blood plasma	In the morning immediately after the Control night
Primary	Baseline Asparagine concentration (mmol/L)	Determined from NMR analysis of blood plasma	In the morning immediately after the Control night
Primary	Baseline Creatine concentration (mmol/L)	Determined from NMR analysis of blood plasma	In the morning immediately after the Control night
Primary	Baseline Creatinine concentration (mmol/L)	Determined from NMR analysis of blood plasma	In the morning immediately after the Control night
Primary	Baseline Glutamic acid concentration (mmol/L)	Determined from NMR analysis of blood plasma	In the morning immediately after the Control night
Primary	Baseline Glutamine concentration (mmol/L)	Determined from NMR analysis of blood plasma	In the morning immediately after the Control night
Primary	Baseline Glycine concentration (mmol/L)	Determined from NMR analysis of blood plasma	In the morning immediately after the Control night
Primary	Baseline Histidine concentration (mmol/L)	Determined from NMR analysis of blood plasma	In the morning immediately after the Control night
Primary	Baseline Isoleucine concentration (mmol/L)	Determined from NMR analysis of blood plasma	In the morning immediately after the Control night
Primary	Baseline Leucine concentration (mmol/L)	Determined from NMR analysis of blood plasma	In the morning immediately after the Control night
Primary	Baseline Lysine concentration (mmol/L)	Determined from NMR analysis of blood plasma	In the morning immediately after the Control night
Primary	Baseline Methionine concentration (mmol/L)	Determined from NMR analysis of blood plasma	In the morning immediately after the Control night
Primary	Baseline N,N-Dimethylglycine concentration (mmol/L)	Determined from NMR analysis of blood plasma	In the morning immediately after the Control night
Primary	Baseline Ornithine concentration (mmol/L)	Determined from NMR analysis of blood plasma	In the morning immediately after the Control night
Primary	Baseline Phenylalanine concentration (mmol/L)	Determined from NMR analysis of blood plasma	In the morning immediately after the Control night
Primary	Baseline Proline concentration (mmol/L)	Determined from NMR analysis of blood plasma	In the morning immediately after the Control night
Primary	Baseline Sarcosine concentration (mmol/L)	Determined from NMR analysis of blood plasma	In the morning immediately after the Control night
Primary	Baseline Threonine concentration (mmol/L)	Determined from NMR analysis of blood plasma	In the morning immediately after the Control night
Primary	Baseline Tyrosine concentration (mmol/L)	Determined from NMR analysis of blood plasma	In the morning immediately after the Control night
Primary	Baseline Valine concentration (mmol/L)	Determined from NMR analysis of blood plasma	In the morning immediately after the Control night
Primary	Baseline 2-Hydroxybutyric acid concentration (mmol/L)	Determined from NMR analysis of blood plasma	In the morning immediately after the Control night
Primary	Baseline Acetic acid concentration (mmol/L)	Determined from NMR analysis of blood plasma	In the morning immediately after the Control night
Primary	Baseline Citric acid concentration (mmol/L)	Determined from NMR analysis of blood plasma	In the morning immediately after the Control night
Primary	Baseline Formic acid concentration (mmol/L)	Determined from NMR analysis of blood plasma	In the morning immediately after the Control night
Primary	Baseline Lactic acid concentration (mmol/L)	Determined from NMR analysis of blood plasma	In the morning immediately after the Control night
Primary	Baseline Succinic acid concentration (mmol/L)	Determined from NMR analysis of blood plasma	In the morning immediately after the Control night
Primary	Baseline Choline concentration (mmol/L)	Determined from NMR analysis of blood plasma	In the morning immediately after the Control night
Primary	Baseline 2-Oxoglutaric acid concentration (mmol/L)	Determined from NMR analysis of blood plasma	In the morning immediately after the Control night
Primary	Baseline 3-Hydroxybutyric acid concentration (mmol/L)	Determined from NMR analysis of blood plasma	In the morning immediately after the Control night
Primary	Baseline Acetoacetic acid concentration (mmol/L)	Determined from NMR analysis of blood plasma	In the morning immediately after the Control night
Primary	Baseline Acetone concentration (mmol/L)	Determined from NMR analysis of blood plasma	In the morning immediately after the Control night
Primary	Baseline Pyruvic acid concentration (mmol/L)	Determined from NMR analysis of blood plasma	In the morning immediately after the Control night
Primary	Baseline D-Galactose concentration (mmol/L)	Determined from NMR analysis of blood plasma	In the morning immediately after the Control night
Primary	Baseline Glucose concentration (mmol/L)	Determined from NMR analysis of blood plasma	In the morning immediately after the Control night
Primary	Baseline Glycerol concentration (mmol/L)	Determined from NMR analysis of blood plasma	In the morning immediately after the Control night
Primary	Baseline Dimethylsulfone concentration (mmol/L)	Determined from NMR analysis of blood plasma	In the morning immediately after the Control night
Primary	Ethanol concentration (mmol/L) after exposure to nocturnal traffic	Determined from NMR analysis of blood plasma	In the morning immediately after the Traffic noise night
Primary	Trimethylamine-N-oxide concentration (mmol/L) after exposure to nocturnal traffic	Determined from NMR analysis of blood plasma	In the morning immediately after the Traffic noise night
Primary	2-Aminobutyric acid concentration (mmol/L) after exposure to nocturnal traffic	Determined from NMR analysis of blood plasma	In the morning immediately after the Traffic noise night
Primary	Alanine concentration (mmol/L) after exposure to nocturnal traffic	Determined from NMR analysis of blood plasma	In the morning immediately after the Traffic noise night
Primary	Asparagine concentration (mmol/L) after exposure to nocturnal traffic	Determined from NMR analysis of blood plasma	In the morning immediately after the Traffic noise night
Primary	Creatine concentration (mmol/L) after exposure to nocturnal traffic	Determined from NMR analysis of blood plasma	In the morning immediately after the Traffic noise night
Primary	Creatinine concentration (mmol/L) after exposure to nocturnal traffic	Determined from NMR analysis of blood plasma	In the morning immediately after the Traffic noise night
Primary	Glutamic acid concentration (mmol/L) after exposure to nocturnal traffic	Determined from NMR analysis of blood plasma	In the morning immediately after the Traffic noise night
Primary	Glutamine concentration (mmol/L) after exposure to nocturnal traffic	Determined from NMR analysis of blood plasma	In the morning immediately after the Traffic noise night
Primary	Glycine concentration (mmol/L) after exposure to nocturnal traffic	Determined from NMR analysis of blood plasma	In the morning immediately after the Traffic noise night
Primary	Histidine concentration (mmol/L) after exposure to nocturnal traffic	Determined from NMR analysis of blood plasma	In the morning immediately after the Traffic noise night
Primary	Isoleucine concentration (mmol/L) after exposure to nocturnal traffic	Determined from NMR analysis of blood plasma	In the morning immediately after the Traffic noise night
Primary	Leucine concentration (mmol/L) after exposure to nocturnal traffic	Determined from NMR analysis of blood plasma	In the morning immediately after the Traffic noise night
Primary	Lysine concentration (mmol/L) after exposure to nocturnal traffic	Determined from NMR analysis of blood plasma	In the morning immediately after the Traffic noise night
Primary	Methionine concentration (mmol/L) after exposure to nocturnal traffic	Determined from NMR analysis of blood plasma	In the morning immediately after the Traffic noise night
Primary	N,N-Dimethylglycine concentration (mmol/L) after exposure to nocturnal traffic	Determined from NMR analysis of blood plasma	In the morning immediately after the Traffic noise night
Primary	Ornithine concentration (mmol/L) after exposure to nocturnal traffic	Determined from NMR analysis of blood plasma	In the morning immediately after the Traffic noise night
Primary	Phenylalanine concentration (mmol/L) after exposure to nocturnal traffic	Determined from NMR analysis of blood plasma	In the morning immediately after the Traffic noise night
Primary	Proline concentration (mmol/L) after exposure to nocturnal traffic	Determined from NMR analysis of blood plasma	In the morning immediately after the Traffic noise night
Primary	Sarcosine concentration (mmol/L) after exposure to nocturnal traffic	Determined from NMR analysis of blood plasma	In the morning immediately after the Traffic noise night
Primary	Threonine concentration (mmol/L) after exposure to nocturnal traffic	Determined from NMR analysis of blood plasma	In the morning immediately after the Traffic noise night
Primary	Tyrosine concentration (mmol/L) after exposure to nocturnal traffic	Determined from NMR analysis of blood plasma	In the morning immediately after the Traffic noise night
Primary	Valine concentration (mmol/L) after exposure to nocturnal traffic	Determined from NMR analysis of blood plasma	In the morning immediately after the Traffic noise night
Primary	2-Hydroxybutyric acid concentration (mmol/L) after exposure to nocturnal traffic	Determined from NMR analysis of blood plasma	In the morning immediately after the Traffic noise night
Primary	Acetic acid concentration (mmol/L) after exposure to nocturnal traffic	Determined from NMR analysis of blood plasma	In the morning immediately after the Traffic noise night
Primary	Citric acid concentration (mmol/L) after exposure to nocturnal traffic	Determined from NMR analysis of blood plasma	In the morning immediately after the Traffic noise night
Primary	Formic acid concentration (mmol/L) after exposure to nocturnal traffic	Determined from NMR analysis of blood plasma	In the morning immediately after the Traffic noise night
Primary	Lactic acid concentration (mmol/L) after exposure to nocturnal traffic	Determined from NMR analysis of blood plasma	In the morning immediately after the Traffic noise night
Primary	Succinic acid concentration (mmol/L) after exposure to nocturnal traffic	Determined from NMR analysis of blood plasma	In the morning immediately after the Traffic noise night
Primary	Choline concentration (mmol/L) after exposure to nocturnal traffic	Determined from NMR analysis of blood plasma	In the morning immediately after the Traffic noise night
Primary	2-Oxoglutaric acid concentration (mmol/L) after exposure to nocturnal traffic	Determined from NMR analysis of blood plasma	In the morning immediately after the Traffic noise night
Primary	3-Hydroxybutyric acid concentration (mmol/L) after exposure to nocturnal traffic	Determined from NMR analysis of blood plasma	In the morning immediately after the Traffic noise night
Primary	Acetoacetic acid concentration (mmol/L) after exposure to nocturnal traffic	Determined from NMR analysis of blood plasma	In the morning immediately after the Traffic noise night
Primary	Acetone concentration (mmol/L) after exposure to nocturnal traffic	Determined from NMR analysis of blood plasma	In the morning immediately after the Traffic noise night
Primary	Pyruvic acid concentration (mmol/L) after exposure to nocturnal traffic	Determined from NMR analysis of blood plasma	In the morning immediately after the Traffic noise night
Primary	D-Galactose concentration (mmol/L) after exposure to nocturnal traffic	Determined from NMR analysis of blood plasma	In the morning immediately after the Traffic noise night
Primary	Glucose concentration (mmol/L) after exposure to nocturnal traffic	Determined from NMR analysis of blood plasma	In the morning immediately after the Traffic noise night
Primary	Glycerol concentration (mmol/L) after exposure to nocturnal traffic	Determined from NMR analysis of blood plasma	In the morning immediately after the Traffic noise night
Primary	Dimethylsulfone concentration (mmol/L) after exposure to nocturnal traffic	Determined from NMR analysis of blood plasma	In the morning immediately after the Traffic noise night
Primary	Ethanol concentration (mmol/L) after exposure to nocturnal pink noise	Determined from NMR analysis of blood plasma	In the morning immediately after the Pink noise night
Primary	Trimethylamine-N-oxide concentration (mmol/L) after exposure to nocturnal pink noise	Determined from NMR analysis of blood plasma	In the morning immediately after the Pink noise night
Primary	2-Aminobutyric acid concentration (mmol/L) after exposure to nocturnal pink noise	Determined from NMR analysis of blood plasma	In the morning immediately after the Pink noise night
Primary	Alanine concentration (mmol/L) after exposure to nocturnal pink noise	Determined from NMR analysis of blood plasma	In the morning immediately after the Pink noise night
Primary	Asparagine concentration (mmol/L) after exposure to nocturnal pink noise	Determined from NMR analysis of blood plasma	In the morning immediately after the Pink noise night
Primary	Creatine concentration (mmol/L) after exposure to nocturnal pink noise	Determined from NMR analysis of blood plasma	In the morning immediately after the Pink noise night
Primary	Creatinine concentration (mmol/L) after exposure to nocturnal pink noise	Determined from NMR analysis of blood plasma	In the morning immediately after the Pink noise night
Primary	Glutamic acid concentration (mmol/L) after exposure to nocturnal pink noise	Determined from NMR analysis of blood plasma	In the morning immediately after the Pink noise night
Primary	Glutamine concentration (mmol/L) after exposure to nocturnal pink noise	Determined from NMR analysis of blood plasma	In the morning immediately after the Pink noise night
Primary	Glycine concentration (mmol/L) after exposure to nocturnal pink noise	Determined from NMR analysis of blood plasma	In the morning immediately after the Pink noise night
Primary	Histidine concentration (mmol/L) after exposure to nocturnal pink noise	Determined from NMR analysis of blood plasma	In the morning immediately after the Pink noise night
Primary	Isoleucine concentration (mmol/L) after exposure to nocturnal pink noise	Determined from NMR analysis of blood plasma	In the morning immediately after the Pink noise night
Primary	Leucine concentration (mmol/L) after exposure to nocturnal pink noise	Determined from NMR analysis of blood plasma	In the morning immediately after the Pink noise night
Primary	Lysine concentration (mmol/L) after exposure to nocturnal pink noise	Determined from NMR analysis of blood plasma	In the morning immediately after the Pink noise night
Primary	Methionine concentration (mmol/L) after exposure to nocturnal pink noise	Determined from NMR analysis of blood plasma	In the morning immediately after the Pink noise night
Primary	N,N-Dimethylglycine concentration (mmol/L) after exposure to nocturnal pink noise	Determined from NMR analysis of blood plasma	In the morning immediately after the Pink noise night
Primary	Ornithine concentration (mmol/L) after exposure to nocturnal pink noise	Determined from NMR analysis of blood plasma	In the morning immediately after the Pink noise night
Primary	Phenylalanine concentration (mmol/L) after exposure to nocturnal pink noise	Determined from NMR analysis of blood plasma	In the morning immediately after the Pink noise night
Primary	Proline concentration (mmol/L) after exposure to nocturnal pink noise	Determined from NMR analysis of blood plasma	In the morning immediately after the Pink noise night
Primary	Sarcosine concentration (mmol/L) after exposure to nocturnal pink noise	Determined from NMR analysis of blood plasma	In the morning immediately after the Pink noise night
Primary	Threonine concentration (mmol/L) after exposure to nocturnal pink noise	Determined from NMR analysis of blood plasma	In the morning immediately after the Pink noise night
Primary	Tyrosine concentration (mmol/L) after exposure to nocturnal pink noise	Determined from NMR analysis of blood plasma	In the morning immediately after the Pink noise night
Primary	Valine concentration (mmol/L) after exposure to nocturnal pink noise	Determined from NMR analysis of blood plasma	In the morning immediately after the Pink noise night
Primary	2-Hydroxybutyric acid concentration (mmol/L) after exposure to nocturnal pink noise	Determined from NMR analysis of blood plasma	In the morning immediately after the Pink noise night
Primary	Acetic acid concentration (mmol/L) after exposure to nocturnal pink noise	Determined from NMR analysis of blood plasma	In the morning immediately after the Pink noise night
Primary	Citric acid concentration (mmol/L) after exposure to nocturnal pink noise	Determined from NMR analysis of blood plasma	In the morning immediately after the Pink noise night
Primary	Formic acid concentration (mmol/L) after exposure to nocturnal pink noise	Determined from NMR analysis of blood plasma	In the morning immediately after the Pink noise night
Primary	Lactic acid concentration (mmol/L) after exposure to nocturnal pink noise	Determined from NMR analysis of blood plasma	In the morning immediately after the Pink noise night
Primary	Succinic acid concentration (mmol/L) after exposure to nocturnal pink noise	Determined from NMR analysis of blood plasma	In the morning immediately after the Pink noise night
Primary	Choline concentration (mmol/L) after exposure to nocturnal pink noise	Determined from NMR analysis of blood plasma	In the morning immediately after the Pink noise night
Primary	2-Oxoglutaric acid concentration (mmol/L) after exposure to nocturnal pink noise	Determined from NMR analysis of blood plasma	In the morning immediately after the Pink noise night
Primary	3-Hydroxybutyric acid concentration (mmol/L) after exposure to nocturnal pink noise	Determined from NMR analysis of blood plasma	In the morning immediately after the Pink noise night
Primary	Acetoacetic acid concentration (mmol/L) after exposure to nocturnal pink noise	Determined from NMR analysis of blood plasma	In the morning immediately after the Pink noise night
Primary	Acetone concentration (mmol/L) after exposure to nocturnal pink noise	Determined from NMR analysis of blood plasma	In the morning immediately after the Pink noise night
Primary	Pyruvic acid concentration (mmol/L) after exposure to nocturnal pink noise	Determined from NMR analysis of blood plasma	In the morning immediately after the Pink noise night
Primary	D-Galactose concentration (mmol/L) after exposure to nocturnal pink noise	Determined from NMR analysis of blood plasma	In the morning immediately after the Pink noise night
Primary	Glucose concentration (mmol/L) after exposure to nocturnal pink noise	Determined from NMR analysis of blood plasma	In the morning immediately after the Pink noise night
Primary	Glycerol concentration (mmol/L) after exposure to nocturnal pink noise	Determined from NMR analysis of blood plasma	In the morning immediately after the Pink noise night
Primary	Dimethylsulfone concentration (mmol/L) after exposure to nocturnal pink noise	Determined from NMR analysis of blood plasma	In the morning immediately after the Pink noise night
Primary	Ethanol concentration (mmol/L) after exposure to nocturnal traffic and pink noise	Determined from NMR analysis of blood plasma	In the morning immediately after the Traffic noise + pink noise night
Primary	Trimethylamine-N-oxide concentration (mmol/L) after exposure to nocturnal traffic and pink noise	Determined from NMR analysis of blood plasma	In the morning immediately after the Traffic noise + pink noise night
Primary	2-Aminobutyric acid concentration (mmol/L) after exposure to nocturnal traffic and pink noise	Determined from NMR analysis of blood plasma	In the morning immediately after the Traffic noise + pink noise night
Primary	Alanine concentration (mmol/L) after exposure to nocturnal traffic and pink noise	Determined from NMR analysis of blood plasma	In the morning immediately after the Traffic noise + pink noise night
Primary	Asparagine concentration (mmol/L) after exposure to nocturnal traffic and pink noise	Determined from NMR analysis of blood plasma	In the morning immediately after the Traffic noise + pink noise night
Primary	Creatine concentration (mmol/L) after exposure to nocturnal traffic and pink noise	Determined from NMR analysis of blood plasma	In the morning immediately after the Traffic noise + pink noise night
Primary	Creatinine concentration (mmol/L) after exposure to nocturnal traffic and pink noise	Determined from NMR analysis of blood plasma	In the morning immediately after the Traffic noise + pink noise night
Primary	Glutamic acid concentration (mmol/L) after exposure to nocturnal traffic and pink noise	Determined from NMR analysis of blood plasma	In the morning immediately after the Traffic noise + pink noise night
Primary	Glutamine concentration (mmol/L) after exposure to nocturnal traffic and pink noise	Determined from NMR analysis of blood plasma	In the morning immediately after the Traffic noise + pink noise night
Primary	Glycine concentration (mmol/L) after exposure to nocturnal traffic and pink noise	Determined from NMR analysis of blood plasma	In the morning immediately after the Traffic noise + pink noise night
Primary	Histidine concentration (mmol/L) after exposure to nocturnal traffic and pink noise	Determined from NMR analysis of blood plasma	In the morning immediately after the Traffic noise + pink noise night
Primary	Isoleucine concentration (mmol/L) after exposure to nocturnal traffic and pink noise	Determined from NMR analysis of blood plasma	In the morning immediately after the Traffic noise + pink noise night
Primary	Leucine concentration (mmol/L) after exposure to nocturnal traffic and pink noise	Determined from NMR analysis of blood plasma	In the morning immediately after the Traffic noise + pink noise night
Primary	Lysine concentration (mmol/L) after exposure to nocturnal traffic and pink noise	Determined from NMR analysis of blood plasma	In the morning immediately after the Traffic noise + pink noise night
Primary	Methionine concentration (mmol/L) after exposure to nocturnal traffic and pink noise	Determined from NMR analysis of blood plasma	In the morning immediately after the Traffic noise + pink noise night
Primary	N,N-Dimethylglycine concentration (mmol/L) after exposure to nocturnal traffic and pink noise	Determined from NMR analysis of blood plasma	In the morning immediately after the Traffic noise + pink noise night
Primary	Ornithine concentration (mmol/L) after exposure to nocturnal traffic and pink noise	Determined from NMR analysis of blood plasma	In the morning immediately after the Traffic noise + pink noise night
Primary	Phenylalanine concentration (mmol/L) after exposure to nocturnal traffic and pink noise	Determined from NMR analysis of blood plasma	In the morning immediately after the Traffic noise + pink noise night
Primary	Proline concentration (mmol/L) after exposure to nocturnal traffic and pink noise	Determined from NMR analysis of blood plasma	In the morning immediately after the Traffic noise + pink noise night
Primary	Sarcosine concentration (mmol/L) after exposure to nocturnal traffic and pink noise	Determined from NMR analysis of blood plasma	In the morning immediately after the Traffic noise + pink noise night
Primary	Threonine concentration (mmol/L) after exposure to nocturnal traffic and pink noise	Determined from NMR analysis of blood plasma	In the morning immediately after the Traffic noise + pink noise night
Primary	Tyrosine concentration (mmol/L) after exposure to nocturnal traffic and pink noise	Determined from NMR analysis of blood plasma	In the morning immediately after the Traffic noise + pink noise night
Primary	Valine concentration (mmol/L) after exposure to nocturnal traffic and pink noise	Determined from NMR analysis of blood plasma	In the morning immediately after the Traffic noise + pink noise night
Primary	2-Hydroxybutyric acid concentration (mmol/L) after exposure to nocturnal traffic and pink noise	Determined from NMR analysis of blood plasma	In the morning immediately after the Traffic noise + pink noise night
Primary	Acetic acid concentration (mmol/L) after exposure to nocturnal traffic and pink noise	Determined from NMR analysis of blood plasma	In the morning immediately after the Traffic noise + pink noise night
Primary	Citric acid concentration (mmol/L) after exposure to nocturnal traffic and pink noise	Determined from NMR analysis of blood plasma	In the morning immediately after the Traffic noise + pink noise night
Primary	Formic acid concentration (mmol/L) after exposure to nocturnal traffic and pink noise	Determined from NMR analysis of blood plasma	In the morning immediately after the Traffic noise + pink noise night
Primary	Lactic acid concentration (mmol/L) after exposure to nocturnal traffic and pink noise	Determined from NMR analysis of blood plasma	In the morning immediately after the Traffic noise + pink noise night
Primary	Succinic acid concentration (mmol/L) after exposure to nocturnal traffic and pink noise	Determined from NMR analysis of blood plasma	In the morning immediately after the Traffic noise + pink noise night
Primary	Choline concentration (mmol/L) after exposure to nocturnal traffic and pink noise	Determined from NMR analysis of blood plasma	In the morning immediately after the Traffic noise + pink noise night
Primary	2-Oxoglutaric acid concentration (mmol/L) after exposure to nocturnal traffic and pink noise	Determined from NMR analysis of blood plasma	In the morning immediately after the Traffic noise + pink noise night
Primary	3-Hydroxybutyric acid concentration (mmol/L) after exposure to nocturnal traffic and pink noise	Determined from NMR analysis of blood plasma	In the morning immediately after the Traffic noise + pink noise night
Primary	Acetoacetic acid concentration (mmol/L) after exposure to nocturnal traffic and pink noise	Determined from NMR analysis of blood plasma	In the morning immediately after the Traffic noise + pink noise night
Primary	Acetone concentration (mmol/L) after exposure to nocturnal traffic and pink noise	Determined from NMR analysis of blood plasma	In the morning immediately after the Traffic noise + pink noise night
Primary	Pyruvic acid concentration (mmol/L) after exposure to nocturnal traffic and pink noise	Determined from NMR analysis of blood plasma	In the morning immediately after the Traffic noise + pink noise night
Primary	D-Galactose concentration (mmol/L) after exposure to nocturnal traffic and pink noise	Determined from NMR analysis of blood plasma	In the morning immediately after the Traffic noise + pink noise night
Primary	Glucose concentration (mmol/L) after exposure to nocturnal traffic and pink noise	Determined from NMR analysis of blood plasma	In the morning immediately after the Traffic noise + pink noise night
Primary	Glycerol concentration (mmol/L) after exposure to nocturnal traffic and pink noise	Determined from NMR analysis of blood plasma	In the morning immediately after the Traffic noise + pink noise night
Primary	Dimethylsulfone concentration (mmol/L) after exposure to nocturnal traffic and pink noise	Determined from NMR analysis of blood plasma	In the morning immediately after the Traffic noise + pink noise night
Secondary	Cardiovascular activation in response to noise	Change in heart rate (ECG)	Event-related, occurring within the time window of each discrete noise event, during each of the five study nights (23:00 to 07:00)
Secondary	Evening subjective sleepiness, assessed using the Karolinska Sleepiness Scale	The scale is a 9-level verbal scale from 1 - "Extremely alert" (best outcome) to 9 - "Very sleepy. great effort to keep alert, fighting sleep" (worst outcome)	Every study evening
Secondary	Morning subjective sleepiness, assessed using the Karolinska Sleepiness Scale	The scale is a 9-level verbal scale from 1 - "Extremely alert" (best outcome) to 9 - "Very sleepy. great effort to keep alert, fighting sleep" (worst outcome)	Every study morning
Secondary	Evening auditory fatigue	Perceived auditory fatigue, self-reported on a 5-point verbal scale, from 1 - "Not at all" (best outcome) to 5 - "Extremely" (worst outcome)	Every study evening
Secondary	Morning auditory fatigue	Perceived auditory fatigue, self-reported on a 5-point verbal scale, from 1 - "Not at all" (best outcome) to 5 - "Extremely" (worst outcome)	Every study morning