Ignite Creation Date:
2024-05-06 @ 10:21 AM
Last Modification Date:
2024-10-26 @ 12:28 PM
Study NCT ID:
NCT03234790
Status:
COMPLETED
Last Update Posted:
2021-11-02
First Post:
2017-07-25
Brief Title:
Human Study to Develop a Signature of Occupational Diesel Exhaust Exposure
Sponsor:
University of British Columbia
Organization:
University of British Columbia
Study Overview
Official Title:
A Controlled Dose-Response Human Study to Develop a Signature of Occupational Diesel Exhaust Exposure
Status:
COMPLETED
Status Verified Date:
2021-10
Last Known Status:
None
Delayed Posting:
No
If Stopped, Why?:
Not Stopped
Has Expanded Access:
False
If Expanded Access, NCT#:
N/A
Has Expanded Access, NCT# Status:
N/A
Acronym:
DICE
Brief Summary:
Strong scientific understanding of how emissions from diesel engines impact the lungs could improve policies and regulations protecting workers exposed to diesel exhaust Accordingly we are recruiting healthy volunteers who are non-smokers to participate in our study Volunteers sit in a room for four hours and breathe either clean filtered air or air that contains pollution at various concentrations similar to occupational settings such as bus and ferry terminals where diesel engines are used A respirologist assesses the volunteers lung health and clinical samples are taken We are equipped with advanced molecular biology tools to measure different molecules and compare samples from our volunteer subjects following exposure to clean air or diesel exhaust Our research aim is to find a simple clinically relevant strategy that can be used to measure the impact of diesel exhaust on workers lung health This knowledge will empower regulators companies and ultimately workers to better manage their health risks Our research aims to provide specific data to help regulators to make informed decisions about the risks of diesel exhaust exposure
Detailed Description:
1 Purpose Over 100000 employees in Alberta are inadvertently exposed to diesel exhaust at work because of wide use of diesel engines in vehicles and machines used in road construction trucking forestry oil extraction and mineral mining Although ambient air monitoring of DE exposure exists in some occupational settings ambient air monitoring depends heavily on surrogate models and may yield a distorted picture of past exhaust exposure Thus a clear exposure limit based on bio-monitoring is needed to adequately protect the workers
2 Objective Our research aims to establish the relationship between exposure concentration and biological effect as an aid to determination of reference ranges for acceptable exposure
3 Hypotheses and Aims
Hypothesis 1 Diesel exhaust DE inhalation elicits a characteristic protein output in a dose-dependent manner
Aim 1 Demonstrate using a proteomic analysis of serum and urine a signature that acutely increases in response to a range of occupationally relevant DE concentrations
Hypothesis 2 DE inhalation increases concentrations of metabolites of polyaromatic hydrocarbons PAH in urine in a dose-dependent manner
Aim 2 Ascertain the range of PAH metabolites accumulation in urine following acute exposure to a range of occupationally relevant DE concentrations
Hypothesis 3 DE inhalation alters the airway responsiveness to a contractile stimulus in a dose-dependent manner and that alteration is associated with changes in a combined proteomicPAH-metabolomic signature
Aim 3 Determine the dose-response slope to methacholine in response to a range of occupationally relevant DE concentrations and correlate changes in this slope to changes in proteins and metabolites
Additionally we aim to establish the relationship between a range of controlled DE exposure concentrations and sleep quality and breathing in sleep through the sub-study component
4 Justification
Our work will inform decision makers and stakeholders in creating evidence-based policies to limit occupational diesel exhaust exposure based on relevant biology
5 Research Method
This is an order-randomized double-blinded crossover human exposure study
This project aims to determine markers of DE exposure that can be used in an occupational setting Therefore we will use a range of occupational exposure levels to appropriately contextualize our results For this 20 healthy participants will be exposed to a control condition and 3 different levels of DE concentration each for a period of 4 hours in a randomized order Each exposure will be separated by a washout period of two weeks The levels will be DE titrated to 20 50 and 150 ugm3 PM25 and the control exposure will be filtered air FA
Participants will undergo a methacholine challenge and will provide urine and blood samples before and after exposures to analyze lung function and biological responses
If participants consent to participation in the sleep sub-study they will be provided with additional questionnaires throughout their visits pertaining to their sleep quality The participants will be provided with an Alice NightOne sleep monitor and instructions on how to operate the equipment The sleep monitor will be hooked up by the participant at home when they are about to sleep following an exposure and will monitor their sleep patterns for that night
6 Statistical Analysis
First the changes in clinical parameters methacholine PC20 and dose response slope and serum blood protein abundance between pre- and post-exposure will be determined These delta values will be statistically compared across exposures using linear mixed effects models using R program as outlined in our previous publications from similarly-designed protocols from our group Values of p005 will be considered significant throughout with adjustments for multiple comparisons Although the 2-week washout period is intended to minimize the likelihood of carryover effects we will formally assess for this by including a term for order of exposures in the models
Analyses for the sleep component will be performed at the Hospital of Ottawa and will be completed through a linear or logistic mixed effects model as applicable using the R program Similar methods to data collected from the main study Data interpretation will be completed through a software algorithm on the local server
2 Objective Our research aims to establish the relationship between exposure concentration and biological effect as an aid to determination of reference ranges for acceptable exposure
3 Hypotheses and Aims
Hypothesis 1 Diesel exhaust DE inhalation elicits a characteristic protein output in a dose-dependent manner
Aim 1 Demonstrate using a proteomic analysis of serum and urine a signature that acutely increases in response to a range of occupationally relevant DE concentrations
Hypothesis 2 DE inhalation increases concentrations of metabolites of polyaromatic hydrocarbons PAH in urine in a dose-dependent manner
Aim 2 Ascertain the range of PAH metabolites accumulation in urine following acute exposure to a range of occupationally relevant DE concentrations
Hypothesis 3 DE inhalation alters the airway responsiveness to a contractile stimulus in a dose-dependent manner and that alteration is associated with changes in a combined proteomicPAH-metabolomic signature
Aim 3 Determine the dose-response slope to methacholine in response to a range of occupationally relevant DE concentrations and correlate changes in this slope to changes in proteins and metabolites
Additionally we aim to establish the relationship between a range of controlled DE exposure concentrations and sleep quality and breathing in sleep through the sub-study component
4 Justification
Our work will inform decision makers and stakeholders in creating evidence-based policies to limit occupational diesel exhaust exposure based on relevant biology
5 Research Method
This is an order-randomized double-blinded crossover human exposure study
This project aims to determine markers of DE exposure that can be used in an occupational setting Therefore we will use a range of occupational exposure levels to appropriately contextualize our results For this 20 healthy participants will be exposed to a control condition and 3 different levels of DE concentration each for a period of 4 hours in a randomized order Each exposure will be separated by a washout period of two weeks The levels will be DE titrated to 20 50 and 150 ugm3 PM25 and the control exposure will be filtered air FA
Participants will undergo a methacholine challenge and will provide urine and blood samples before and after exposures to analyze lung function and biological responses
If participants consent to participation in the sleep sub-study they will be provided with additional questionnaires throughout their visits pertaining to their sleep quality The participants will be provided with an Alice NightOne sleep monitor and instructions on how to operate the equipment The sleep monitor will be hooked up by the participant at home when they are about to sleep following an exposure and will monitor their sleep patterns for that night
6 Statistical Analysis
First the changes in clinical parameters methacholine PC20 and dose response slope and serum blood protein abundance between pre- and post-exposure will be determined These delta values will be statistically compared across exposures using linear mixed effects models using R program as outlined in our previous publications from similarly-designed protocols from our group Values of p005 will be considered significant throughout with adjustments for multiple comparisons Although the 2-week washout period is intended to minimize the likelihood of carryover effects we will formally assess for this by including a term for order of exposures in the models
Analyses for the sleep component will be performed at the Hospital of Ottawa and will be completed through a linear or logistic mixed effects model as applicable using the R program Similar methods to data collected from the main study Data interpretation will be completed through a software algorithm on the local server
Study Oversight
Has Oversight DMC:
None
Is a FDA Regulated Drug?:
False
Is a FDA Regulated Device?:
False
Is an Unapproved Device?:
None
Is a PPSD?:
None
Is a US Export?:
None
Is an FDA AA801 Violation?:
None