Effects of Railway Vibration on Sleep and Disease

This study will investigate the biological mechanisms linking sleep disruption by vibration and noise, and the development of cardiometabolic disease. In a laboratory sleep study, the investigators will play railway vibration of different levels during the night. The investigators 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 analyzed to identify metabolic changes and indicators of diabetes risk in different nights. Identifying biomarkers that are impacted by sleep fragmentation will establish the currently unclear pathways by which railway vibration exposure at night can lead to the development of diseases in the long term, especially metabolic disorders including diabetes.

The experimental sleep study has the overarching goal of deepening understanding of sleep disruption by railway vibration and noise and changes in cardiometabolic and cognitive function. To this end, the study will address the following study aim:

Aim 1: Determine the biological and neurobehavioral consequences of sleep disruption by railway vibration. The investigators will measure the sleep of healthy volunteers, and each morning will obtain blood samples for metabolomics metabolic function analysis and administer a neurocognitive test battery. The investigators will compare effects on sleep, metabolomics, metabolic function and cognitive function between quiet nights and nights with railway traffic vibration and noise. Dose-response relationships will be determined by comparing nights with different levels of vibration.

This study will take place in the sound environment laboratory (SEL) at the University of Gothenburg Department of Occupational and Environmental Medicine. 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 and electrodynamic transducers mounted to the underside of each bed allow the investigators to create a realistic acoustic environment by transmitting sound and vibration exposures from the control room to each bedroom individually. The investigators have shown previously that results from this lab with high ecological validity are comparable with results from the field.

This study has a prospective within-subjects cross-over design. Participants (total N=24) 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 familiarization with the test procedures. The second night will be a quiet condition without noise or vibration, to determine normal baseline sleep, cardiometabolic profile, and cognitive performance. Study nights 3-5 are the vibration nights and will be randomly assigned across participants using a Latin square design to avoid first-order carryover effects. In these vibration nights, vibration and noise from railway freight will be played into the bedrooms to determine the effects of vibration and noise on sleep, cardiometabolic function and cognitive performance. Thirty six trains will occur each night, randomly distributed across the 8-hour sleep period.

For railway vibration the investigators will use synthesized signals based on measured data, used in previous laboratory studies. It is necessary to use synthesized vibration, rather than recorded signals, so that the investigators can accurately adjust the acoustical character of the exposure as needed. Railway vibration will be accompanied by high fidelity recordings of railway freight noise. This is to maximize ecological validity of the exposures since vibration rarely occurs without noise, and to mask any mechanical sounds from the vibration transducers.

Vibration and noise exposures will reflect realistic railway freight traffic noise levels that occur in dwellings alongside railway lines in Sweden. The maximum Wm-weighted vibration amplitudes in the three vibration nights will be 0.5 mm/s, 0.7 mm/s and 0.9 mm/s respectively. Maximum sound pressure levels of individual train passages will not exceed 49.8 dB LAF,max. Trains will vary from 11.5 s to 56.9 s in duration. All vibration amplitudes will be calibrated on the mattress of the bed, under a 75 kg reference weight to simulate the bed being occupied. All sound pressure levels will be calibrated to 10 cm above the pillow in each bedroom prior to the study, so that these levels accurately reflect the noise exposure of the subjects during sleep.

Each night the investigators will record physiologic sleep with polysomnography (PSG) and cardiac activity with electrocardiography (ECG). Each study morning, subjects will provide a 2ml blood sample 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 extreme and/or variable dietary behavior 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, 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. Furthermore, a 2-hour oral glucose tolerance test (OGTT) will be performed in the mornings after the quiet control night (i.e. after study night 2) and after the third vibration exposure night (i.e. after study night 5). The investigators will measure response to a 75g glucose bolus at timepoints 10, 20, 30, 60, 90 and 120 minutes after the glucose administration.

Each evening, subjects will complete a computerized 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 analyzed 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.

Eligibility Criteria:
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. diagnosed with diabetes
8. indications of sleep apnea on the STOP-BANG questionnaire;
9. shift work;
10. smoking, vaping, snus, or other nicotine use;
11. pregnant or breastfeeding