Metabolic and Cognitive Consequences of Noise-induced Sleep Disturbance

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.

Study Overview

• Status: Completed
• Conditions: Cognitive Change; Sleep Disturbance; Metabolic Disturbance; Noise Exposure; Sleep Hygiene
• Intervention / Treatment: Radiation: Traffic noise; Radiation: Pink noise exposure

Detailed 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.

• Study Type: Interventional
• Enrollment (Actual): 12
• Phase: Not Applicable

Contacts and Locations

Study Locations

• Sweden
  • Västra Götaland
    • Gothenburg, Västra Götaland, Sweden, 42650
      • University of Gothenburg

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 30 years (ADULT)
• Accepts Healthy Volunteers: Yes
• Genders Eligible for Study: All

Description

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.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: BASIC_SCIENCE
• Allocation: RANDOMIZED
• Interventional Model: CROSSOVER
• Masking: DOUBLE

Number of Arms

4

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
NO_INTERVENTION: Control; Single study night with no noise exposure, to determine normal baseline sleep
EXPERIMENTAL: Traffic noise; Single study night with traffic noise events, to determine consequences of sleep disturbance by traffic noise	Radiation: 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.
EXPERIMENTAL: Pink noise; Single study night to measure the effects of a non-pharmacological intervention to promote sleep, pink noise.	Radiation: Pink noise exposure; Continuous pink noise sound exposure at 45 dBA, throughout the whole night
EXPERIMENTAL: Traffic noise + pink noise; Single study night with concurrent traffic noise events and continuous pink noise sound exposure. Night is used to determine attenuation of sleep disturbance by traffic noise due to introduction of pink noise.	Radiation: 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.; Radiation: Pink noise exposure; Continuous pink noise sound exposure at 45 dBA, throughout the whole night

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
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
Baseline total sleep time	Measured via polysomnography/EEG, scored according to American Academy of Sleep Medicine guidelines	During the Control night
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
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
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
Total amount of baseline N1 sleep	Measured via polysomnography/EEG, scored according to American Academy of Sleep Medicine guidelines	During the Control night
Total amount of baseline N2 sleep	Measured via polysomnography/EEG, scored according to American Academy of Sleep Medicine guidelines	During the Control night
Total amount of baseline N3 sleep	Measured via polysomnography/EEG, scored according to American Academy of Sleep Medicine guidelines	During the Control night
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
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
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
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
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
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
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
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
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
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
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
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
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
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
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
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
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
Baseline number of awakenings	Measured via polysomnography/EEG, scored according to American Academy of Sleep Medicine guidelines	During the Control night
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
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
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
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
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
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
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
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
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
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
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
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
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
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
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
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
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
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
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
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
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
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
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
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
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
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
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
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
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
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
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
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
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
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
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
Baseline Ethanol concentration (mmol/L)	Determined from NMR analysis of blood plasma	In the morning immediately after the Control night
Baseline Trimethylamine-N-oxide concentration (mmol/L)	Determined from NMR analysis of blood plasma	In the morning immediately after the Control night
Baseline 2-Aminobutyric acid concentration (mmol/L)	Determined from NMR analysis of blood plasma	In the morning immediately after the Control night
Baseline Alanine concentration (mmol/L)	Determined from NMR analysis of blood plasma	In the morning immediately after the Control night
Baseline Asparagine concentration (mmol/L)	Determined from NMR analysis of blood plasma	In the morning immediately after the Control night
Baseline Creatine concentration (mmol/L)	Determined from NMR analysis of blood plasma	In the morning immediately after the Control night
Baseline Creatinine concentration (mmol/L)	Determined from NMR analysis of blood plasma	In the morning immediately after the Control night
Baseline Glutamic acid concentration (mmol/L)	Determined from NMR analysis of blood plasma	In the morning immediately after the Control night
Baseline Glutamine concentration (mmol/L)	Determined from NMR analysis of blood plasma	In the morning immediately after the Control night
Baseline Glycine concentration (mmol/L)	Determined from NMR analysis of blood plasma	In the morning immediately after the Control night
Baseline Histidine concentration (mmol/L)	Determined from NMR analysis of blood plasma	In the morning immediately after the Control night
Baseline Isoleucine concentration (mmol/L)	Determined from NMR analysis of blood plasma	In the morning immediately after the Control night
Baseline Leucine concentration (mmol/L)	Determined from NMR analysis of blood plasma	In the morning immediately after the Control night
Baseline Lysine concentration (mmol/L)	Determined from NMR analysis of blood plasma	In the morning immediately after the Control night
Baseline Methionine concentration (mmol/L)	Determined from NMR analysis of blood plasma	In the morning immediately after the Control night
Baseline N,N-Dimethylglycine concentration (mmol/L)	Determined from NMR analysis of blood plasma	In the morning immediately after the Control night
Baseline Ornithine concentration (mmol/L)	Determined from NMR analysis of blood plasma	In the morning immediately after the Control night
Baseline Phenylalanine concentration (mmol/L)	Determined from NMR analysis of blood plasma	In the morning immediately after the Control night
Baseline Proline concentration (mmol/L)	Determined from NMR analysis of blood plasma	In the morning immediately after the Control night
Baseline Sarcosine concentration (mmol/L)	Determined from NMR analysis of blood plasma	In the morning immediately after the Control night
Baseline Threonine concentration (mmol/L)	Determined from NMR analysis of blood plasma	In the morning immediately after the Control night
Baseline Tyrosine concentration (mmol/L)	Determined from NMR analysis of blood plasma	In the morning immediately after the Control night
Baseline Valine concentration (mmol/L)	Determined from NMR analysis of blood plasma	In the morning immediately after the Control night
Baseline 2-Hydroxybutyric acid concentration (mmol/L)	Determined from NMR analysis of blood plasma	In the morning immediately after the Control night
Baseline Acetic acid concentration (mmol/L)	Determined from NMR analysis of blood plasma	In the morning immediately after the Control night
Baseline Citric acid concentration (mmol/L)	Determined from NMR analysis of blood plasma	In the morning immediately after the Control night
Baseline Formic acid concentration (mmol/L)	Determined from NMR analysis of blood plasma	In the morning immediately after the Control night
Baseline Lactic acid concentration (mmol/L)	Determined from NMR analysis of blood plasma	In the morning immediately after the Control night
Baseline Succinic acid concentration (mmol/L)	Determined from NMR analysis of blood plasma	In the morning immediately after the Control night
Baseline Choline concentration (mmol/L)	Determined from NMR analysis of blood plasma	In the morning immediately after the Control night
Baseline 2-Oxoglutaric acid concentration (mmol/L)	Determined from NMR analysis of blood plasma	In the morning immediately after the Control night
Baseline 3-Hydroxybutyric acid concentration (mmol/L)	Determined from NMR analysis of blood plasma	In the morning immediately after the Control night
Baseline Acetoacetic acid concentration (mmol/L)	Determined from NMR analysis of blood plasma	In the morning immediately after the Control night
Baseline Acetone concentration (mmol/L)	Determined from NMR analysis of blood plasma	In the morning immediately after the Control night
Baseline Pyruvic acid concentration (mmol/L)	Determined from NMR analysis of blood plasma	In the morning immediately after the Control night
Baseline D-Galactose concentration (mmol/L)	Determined from NMR analysis of blood plasma	In the morning immediately after the Control night
Baseline Glucose concentration (mmol/L)	Determined from NMR analysis of blood plasma	In the morning immediately after the Control night
Baseline Glycerol concentration (mmol/L)	Determined from NMR analysis of blood plasma	In the morning immediately after the Control night
Baseline Dimethylsulfone concentration (mmol/L)	Determined from NMR analysis of blood plasma	In the morning immediately after the Control night
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
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
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
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
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
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
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
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
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
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
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
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
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
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
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
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
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
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
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
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
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
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
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
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
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
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
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
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
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
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
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
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
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
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
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
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
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
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
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
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
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
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
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
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
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
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
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
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
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
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
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
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
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
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
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
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
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
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
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
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
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
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
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
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
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
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
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
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
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
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
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
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
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
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
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
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
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
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
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
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
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
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
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
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
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
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
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
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
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
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
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
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
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
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
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
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
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
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
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
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
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
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
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
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
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
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
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
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
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
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
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
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
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
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
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
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
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 Outcome Measures

Outcome Measure	Measure Description	Time Frame
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)
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
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
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
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

Collaborators and Investigators

• Sponsor: Göteborg University
• Collaborators: University of Manitoba; University of Pennsylvania

Study record dates

Study Major Dates

• Study Start (ACTUAL): April 24, 2022
• Primary Completion (ACTUAL): June 3, 2022
• Study Completion (ACTUAL): June 3, 2022

Study Registration Dates

• First Submitted: March 9, 2022
• First Submitted That Met QC Criteria: March 31, 2022
• First Posted (ACTUAL): April 8, 2022

Study Record Updates

• Last Update Posted (ACTUAL): June 22, 2022
• Last Update Submitted That Met QC Criteria: June 16, 2022
• Last Verified: June 1, 2022

More Information

Terms related to this study

• Keywords: polysomnography; metabolomics; neurobehavioral performance; white noise; auditory fatigue
• Additional Relevant MeSH Terms: Mental Disorders; Nervous System Diseases; Sleep Wake Disorders; Dyssomnias; Parasomnias
• Other Study ID Numbers: 234826201

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