Metabolic and Cognitive Consequences of Noise-induced Sleep Disturbance
Condition: Noise Exposure; Sleep Disturbance; Sleep Hygiene; Metabolic Disturbance; Cognitive Change
MeSH terms: Dyssomnias; Parasomnias
Study type: Interventional

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.
    

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.
    

Intervention name(s): Pink noise exposure; Traffic noise
Intervention type(s): Radiation; Radiation
Intervention description(s): Continuous pink noise sound exposure at 45 dBA, throughout the whole night; 120 traffic noise events (40 each of road, rail and aircraft), introduced at maximum sound pressure levels ranging between 45-65 dB LAS.max.
Allocation: Randomized
Intervention model: Crossover Assignment
Intervention model description: All participants will be exposed to each of the different noise exposure conditions. Each study night is treated as a separate arm of the crossover study. The order of the noise exposure conditions will be 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.
Masking: Double (Participant, Outcomes Assessor)
Primary purpose: Basic Science
Keywords: neurobehavioral performance; white noise; auditory fatigue; polysomnography; metabolomics