Circadian Rhythm Disruption Effects on Smoke Inhalation

NCT ID: NCT04955431

Last Updated: 2025-05-30

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: NA
• Total Enrollment: 10 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2022-01-24
• Study Completion Date: 2022-04-17

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.

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/m^3, and RS-250: Restricted Sleep with exposure to woodsmoke at 250 µg/m^3. 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.

Conditions

Inflammation; Sleep Deprivation; Circadian Rhythm Sleep Disorder, Shift Work Type; Smoke Inhalation

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: CROSSOVER
• Primary Study Purpose: BASIC_SCIENCE
• Blinding Strategy: NONE

Study Groups

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).

Group Type: PLACEBO_COMPARATOR

Normal Sleep

Intervention Type: BEHAVIORAL

Participants will be allowed \~8 hour sleep opportunity the night of sleep prior to reporting to lab for a simulated firefighting session.

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).

Group Type: EXPERIMENTAL

Sleep Restriction

Intervention Type: BEHAVIORAL

Participants will be allowed \~4 hour sleep opportunity during the restricted night of sleep prior to reporting to lab for a simulated firefighting session.

Interventions

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.

Intervention Type: 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.

Intervention Type: BEHAVIORAL

Other Intervention Names

Circadian Rhythm Disruption; SR; NS

Eligibility Criteria

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)

• Minimum Eligible Age: 18 Years
• Maximum Eligible Age: 44 Years
• Eligible Sex: MALE
• Accepts Healthy Volunteers: Yes

Sponsors

University of Nevada, Las Vegas

OTHER

Sponsor Role: collaborator

University of Montana

OTHER

Sponsor Role: lead

Responsible Party

John Quindry

Professor and Chair

Responsibility Role: PRINCIPAL_INVESTIGATOR

Principal Investigators

John C Quindry, PhD

Role: PRINCIPAL_INVESTIGATOR

University of Montana

Locations

School of Integrative Physiology and Athletic Training

Missoula, Montana, United States

Countries

United States

Provided Documents

Document Type: Study Protocol and Informed Consent Form

View Document

Document Type: Statistical Analysis Plan

View Document

Other Identifiers

IRB# is 83-21

Identifier Type: -

Identifier Source: org_study_id