Circadian Rhythm Disruption Effects on Smoke Inhalation

Sponsor
University of Montana (Other)
Overall Status
Recruiting
CT.gov ID
NCT04955431
Collaborator
University of Nevada, Las Vegas (Other)
12
1
2
5.7
2.1

Study Details

Study Description

Brief Summary

Particulate matter exposure during smoke inhalation provokes inflammatory immune responses in people exposed to burning biomass including fire fighters and civilians. Persistent occupational exposure to particulate matter represents a unique hazard for firefighters, underpinning a burgeoning research area. This trial will evaluate the effects of sleep deprivation and circadian rhythm disruption on the inflammatory response to woodsmoke associated particulate matter exposure. Participants will undergo 2 experimental trials in a randomized cross-over design. Participants will have either an 8-hour sleep opportunity or a 4-hour sleep opportunity prior to reporting to lab for a 45 minute simulated firefighting trial (wood smoke associated particulate matter filtered to 2.5 um at a concentration of 250 ug/m^3, while exercising at a moderate intensity). The effects of sleep restriction and simulated firefighting will be measured.

Condition or Disease Intervention/Treatment Phase
  • Behavioral: Sleep Restriction
  • Behavioral: Normal Sleep
N/A

Detailed Description

Participants: Healthy college age males (n = 15), free from disordered sleep and without recent trans-meridian travel (within the last 2 weeks) will be recruited for this study. Participants will complete chronotype questionnaires (Morningness-Eveningness Questionnaire; MEQ, Munich Chronotype Questionnaire; MCTQ) to establish intermediate chronotypes. This will minimize the effect of circadian preference on the morning exposure to smoke. Participants will subsequently be outfitted with activity monitors (ActiCal) to monitor sleep and physical activity throughout the experimental duration. Participants will be asked to maintain a normal sleep schedule for at least 3 days leading up to the experimental trials and keep a sleep log to verify.

Experimental Trials: Participants will undergo 2 experimental trials in a randomized cross-over design, with at least 1 week washout period between trials; 1) NS-250: Normal Sleep with exposure to woodsmoke at 250 µg/m3, and RS-250: Restricted Sleep with exposure to woodsmoke at 250 µg/m3. Participants will have an 8-hour sleep opportunity in their own home during the NS trials (22:00-06:00), and a 4-hour sleep opportunity during the RS trials (00:00-04:00). In all trials, participants will report to the laboratory at 07:30 the morning after the experimental sleep night. PM exposure will occur from 08:00-08:45 while cycling at 70% heart rate reserve (HRR) to simulate the physical demands of firefighting.

Exhaled Breath Condensate (EBC): EBC will be collected using standardized 10 minute collection techniques. In order to preserve sample integrity for potentially labile biomarkers (e.g., oxidative stress), sample pH will be measured immediately prior to aliquoting in multiple cryotubes (500-700µl), flash freezing, and storage at -80 degrees C until further assay. Standardized biomarker panels for oxidative stress and inflammation will be performed using a single thaw approach.

Inflammatory biomarker analysis: Blood will be collected into heparinized vacutainers before (PRE) and immediately following (POST) PM2.5 exposure and spun down for plasma collection. Plasma will be assayed for inflammatory biomarkers (interleukin (IL)-6, tumor necrosis factor (TNF)-α, pentraxin-3, and C-reactive protein (CRP)) using standard enzyme linked immunosorbent assays (ELISA).

Circadian Rhythm Assessment: Throughout the experimental protocol, circadian rhythms will be assessed in two ways; 1) Actigraphy and 2) Clock gene expression in buccal cell swabs. Acticals will be worn throughout to gather sleep variables (timing, duration, quality). Clock gene expression (CLOCK, BMAL1, PER2) will be measured in swabs taken from the cheek at 6 hour intervals (00:00, 06:00, 12:00, 18:00) to assess the effects of sleep deprivation on the molecular circadian rhythm. Cheek swabs will be immediately placed in RNA stabilization buffer until isolation. Swabs taken at 00:00 will be performed with minimal exposure to light to avoid disruption of sleep. These methods have been used previously to assess normal and disrupted sleep.

Study Design

Study Type:
Interventional
Anticipated Enrollment :
12 participants
Allocation:
Randomized
Intervention Model:
Crossover Assignment
Intervention Model Description:
Randomized cross-over designRandomized cross-over design
Masking:
None (Open Label)
Primary Purpose:
Basic Science
Official Title:
The Effects of Circadian Rhythm Disruption on the Inflammatory Response to Particulate Matter Exposure From Woodsmoke
Actual Study Start Date :
Jan 24, 2022
Actual Primary Completion Date :
Mar 21, 2022
Anticipated Study Completion Date :
Jul 17, 2022

Arms and Interventions

Arm Intervention/Treatment
Placebo Comparator: Normal Sleep (with 250 ug/m^3 PM2.5)

Participants will have a normal sleep opportunity the night prior to reporting to the lab for the simulated firefighting session (250 ug/m^3 PM2.5 with moderate intensity exercise).

Behavioral: Normal Sleep
Participants will be allowed ~8 hour sleep opportunity the night of sleep prior to reporting to lab for a simulated firefighting session.
Other Names:
  • NS
  • Experimental: Restricted Sleep (with 250 ug/m^3 PM2.5)

    Participants will have a restricted sleep opportunity (~4 hours) the night prior to reporting to the lab for the simulated firefighting session (250 ug/m^3 PM2.5 with moderate intensity exercise).

    Behavioral: Sleep Restriction
    Participants will be allowed ~4 hour sleep opportunity during the restricted night of sleep prior to reporting to lab for a simulated firefighting session.
    Other Names:
  • Circadian Rhythm Disruption
  • SR
  • Outcome Measures

    Primary Outcome Measures

    1. Blood Inflammation [samples collected immediately post exposure will be compared to pre-exposure]

      IL-6 will be measured in the plasma

    Secondary Outcome Measures

    1. Exhaled Breath Condensate [samples collected immediately post exposure will be compared to pre-exposure]

      Pentraxin-3 will be measured in EBC

    Other Outcome Measures

    1. Circadian clock gene expression disruption [sampled collected every 6 hours for 24 hours prior to exposure]

      Clock genes will be measured over a 24 hour time-course with and without sleep restriction

    Eligibility Criteria

    Criteria

    Ages Eligible for Study:
    18 Years to 44 Years
    Sexes Eligible for Study:
    Male
    Accepts Healthy Volunteers:
    Yes
    Inclusion Criteria:
    • Healthy

    • Male

    • 18 - 44 years of age

    Exclusion Criteria:
    • Preexisting cardiometabolic and/or pulmonary diseases

    • Preexisting sleep disorder

    • Smoking (current or within last year)

    Contacts and Locations

    Locations

    Site City State Country Postal Code
    1 School of Integrative Physiology and Athletic Training Missoula Montana United States 59812

    Sponsors and Collaborators

    • University of Montana
    • University of Nevada, Las Vegas

    Investigators

    • Principal Investigator: John C Quindry, PhD, University of Montana

    Study Documents (Full-Text)

    None provided.

    More Information

    Publications

    None provided.
    Responsible Party:
    John Quindry, Professor and Chair, University of Montana
    ClinicalTrials.gov Identifier:
    NCT04955431
    Other Study ID Numbers:
    • IRB# is 83-21
    First Posted:
    Jul 8, 2021
    Last Update Posted:
    Jun 10, 2022
    Last Verified:
    Jun 1, 2022
    Individual Participant Data (IPD) Sharing Statement:
    No
    Plan to Share IPD:
    No
    Studies a U.S. FDA-regulated Drug Product:
    No
    Studies a U.S. FDA-regulated Device Product:
    No
    Additional relevant MeSH terms:

    Study Results

    No Results Posted as of Jun 10, 2022