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Circadian Rhythm Disruption Effects on Smoke Inhalation

Primary Purpose

Inflammation, Sleep Deprivation, Circadian Rhythm Sleep Disorder, Shift Work Type

Status
Completed
Phase
Not Applicable
Locations
United States
Study Type
Interventional
Intervention
Sleep Restriction
Normal Sleep
Sponsored by
University of Montana
About
Eligibility
Locations
Arms
Outcomes
Full info

About this trial

This is an interventional basic science trial for Inflammation

Eligibility Criteria

18 Years - 44 Years (Adult)MaleAccepts Healthy Volunteers

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)

Sites / Locations

  • School of Integrative Physiology and Athletic Training

Arms of the Study

Arm 1

Arm 2

Arm Type

Placebo Comparator

Experimental

Arm Label

Normal Sleep (with 250 ug/m^3 PM2.5)

Restricted Sleep (with 250 ug/m^3 PM2.5)

Arm Description

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).

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).

Outcomes

Primary Outcome Measures

Blood Inflammation
IL-6 will be measured in the plasma

Secondary Outcome Measures

Exhaled Breath Condensate
Pentraxin-3 will be measured in EBC

Full Information

First Posted
June 21, 2021
Last Updated
March 6, 2023
Sponsor
University of Montana
Collaborators
University of Nevada, Las Vegas
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1. Study Identification

Unique Protocol Identification Number
NCT04955431
Brief Title
Circadian Rhythm Disruption Effects on Smoke Inhalation
Official Title
The Effects of Circadian Rhythm Disruption on the Inflammatory Response to Particulate Matter Exposure From Woodsmoke
Study Type
Interventional

2. Study Status

Record Verification Date
June 2022
Overall Recruitment Status
Completed
Study Start Date
January 24, 2022 (Actual)
Primary Completion Date
March 17, 2022 (Actual)
Study Completion Date
April 17, 2022 (Actual)

3. Sponsor/Collaborators

Responsible Party, by Official Title
Principal Investigator
Name of the Sponsor
University of Montana
Collaborators
University of Nevada, Las Vegas

4. Oversight

Studies a U.S. FDA-regulated Drug Product
No
Studies a U.S. FDA-regulated Device Product
No
Data Monitoring Committee
No

5. 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.
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.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Inflammation, Sleep Deprivation, Circadian Rhythm Sleep Disorder, Shift Work Type, Smoke Inhalation

7. Study Design

Primary Purpose
Basic Science
Study Phase
Not Applicable
Interventional Study Model
Crossover Assignment
Model Description
Randomized cross-over design
Masking
None (Open Label)
Allocation
Randomized
Enrollment
10 (Actual)

8. Arms, Groups, and Interventions

Arm Title
Normal Sleep (with 250 ug/m^3 PM2.5)
Arm Type
Placebo Comparator
Arm Description
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).
Arm Title
Restricted Sleep (with 250 ug/m^3 PM2.5)
Arm Type
Experimental
Arm Description
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).
Intervention Type
Behavioral
Intervention Name(s)
Sleep Restriction
Other Intervention Name(s)
Circadian Rhythm Disruption, SR
Intervention Description
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
Intervention Name(s)
Normal Sleep
Other Intervention Name(s)
NS
Intervention Description
Participants will be allowed ~8 hour sleep opportunity the night of sleep prior to reporting to lab for a simulated firefighting session.
Primary Outcome Measure Information:
Title
Blood Inflammation
Description
IL-6 will be measured in the plasma
Time Frame
samples collected immediately post exposure will be compared to pre-exposure
Secondary Outcome Measure Information:
Title
Exhaled Breath Condensate
Description
Pentraxin-3 will be measured in EBC
Time Frame
samples collected immediately post exposure will be compared to pre-exposure
Other Pre-specified Outcome Measures:
Title
Circadian clock gene expression disruption
Description
Clock genes will be measured over a 24 hour time-course with and without sleep restriction
Time Frame
sampled collected every 6 hours for 24 hours prior to exposure

10. Eligibility

Sex
Male
Minimum Age & Unit of Time
18 Years
Maximum Age & Unit of Time
44 Years
Accepts Healthy Volunteers
Accepts Healthy Volunteers
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)
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
John C Quindry, PhD
Organizational Affiliation
University of Montana
Official's Role
Principal Investigator
Facility Information:
Facility Name
School of Integrative Physiology and Athletic Training
City
Missoula
State/Province
Montana
ZIP/Postal Code
59812
Country
United States

12. IPD Sharing Statement

Plan to Share IPD
No
IPD Sharing Plan Description
Individual participant data will not be shared with other researchers. Blinded anonymized outcomes data will be shared via publication and presentation of results.

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Circadian Rhythm Disruption Effects on Smoke Inhalation

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