BioTrack: Health Effects of Occupational Exposure to Combustion Particles - a Study on Volunteers Performing as Train Conductors

Sponsor

University of Copenhagen (Other)

Overall Status

Completed

CT.gov ID

NCT03104387

Collaborator

National Research Centre for the Working Environment, Denmark (Other)

Enrollment

Location

Arms

35.5

Actual Duration (Months)

0.8

Patients Per Site Per Month

Study Details

Study Description

Brief Summary

Ambient air pollution is a complex mixture of gaseous pollutants and particulate matter (PM). PM has a recognized important role in human health. There is a strong scientific consensus on the independent association of PM and adverse cardiovascular and respiratory effects, as well as cancer. It is reasonable to expect that the smaller particles (ultrafine particles, UFP) may have an enhanced toxicity relative to other PM size fractions, due to physical properties and potential to translocation beyond the lung.

A recent Danish report concluded that train conductors on a working day, and in two specific diesel engine trains, are exposed to higher concentrations of diesel exhaust than by constant stay in a busy street. Indeed, the average exposure for train conductors on such engines was around 100,000-150,000 UFP per cm3 as compared with around 40,000 per cm3 on a busy street in Copenhagen [1]. The aim of this study is to investigate if this occupational exposure is associated with vascular and respiratory impairment and DNA damage.

Condition or Disease	Intervention/Treatment	Phase
Cardiovascular Function Genotoxicity	Other: Electric train Other: Diesel train	N/A

Study Design

Study Type:

Interventional

Actual Enrollment :

29 participants

Allocation:

Randomized

Intervention Model:

Crossover Assignment

Masking:

None (Open Label)

Primary Purpose:

Basic Science

Official Title:

Effects of Diesel Combustion Generated Air Pollution on Cardiovascular Function and Oxidatively Damaged DNA in Healthy Volunteers

Actual Study Start Date :

May 16, 2017

Actual Primary Completion Date :

Sep 30, 2018

Actual Study Completion Date :

May 1, 2020

Arms and Interventions

Arm	Intervention/Treatment
Experimental: Diesel train - exposure scenario The same study person will be exposed to two different scenarios, at different times and for three consecutive days. It will be a lag time of 2 weeks between each exposure scenario. The "exposure" scenario is defined as a workday (6 hours) on the diesel ME-driven model regional train. The Diesel Train Scenario is performed twice. After the scenario completion (on the third day in defined train routes) the vascular function, lung function, blood and urine samplings are performed.	Other: Diesel train Exposure to air with high level of ultrafine particles (Diesel train)
Sham Comparator: Electric train - low exposure scenario The same study person will be exposed to two different scenarios, at different times and for three consecutive days. It will be a lag time of 2 weeks between each exposure scenario. The "low exposure" scenario is defined as a workday (6 hours) on the electric train. The Diesel Train Scenario is performed twice. After the scenario completion (on the third day in defined train routes) the vascular function, lung function, blood and urine samplings are performed.	Other: Electric train Exposure to air with low level of ultrafine particles (Electric train)

Arm

Intervention/Treatment

Experimental: Diesel train - exposure scenario

The same study person will be exposed to two different scenarios, at different times and for three consecutive days. It will be a lag time of 2 weeks between each exposure scenario. The "exposure" scenario is defined as a workday (6 hours) on the diesel ME-driven model regional train. The Diesel Train Scenario is performed twice. After the scenario completion (on the third day in defined train routes) the vascular function, lung function, blood and urine samplings are performed.

Other: Diesel train

Exposure to air with high level of ultrafine particles (Diesel train)

Sham Comparator: Electric train - low exposure scenario

The same study person will be exposed to two different scenarios, at different times and for three consecutive days. It will be a lag time of 2 weeks between each exposure scenario. The "low exposure" scenario is defined as a workday (6 hours) on the electric train. The Diesel Train Scenario is performed twice. After the scenario completion (on the third day in defined train routes) the vascular function, lung function, blood and urine samplings are performed.

Other: Electric train

Exposure to air with low level of ultrafine particles (Electric train)

Outcome Measures

Primary Outcome Measures

Reactive hyperemia index measured by peripheral arterial tonometry [Peripheral arterial tonometry is assessed after each exposure scenario (on the third day after 6 hours on defined train routes per day)]
The primary outcome will be measured in the form of post-ischemic variation followed by the measurement of the vasomotor function after the administration of nitroglycerin, to allow the investigation of the endothelium independent vasodilatation. The portable device EndoPAT 2000 will be used (Itamar Medical Ltd, Israel) [2-6].
Heart rate variability [Assessed after each exposure scenario (on the third day after 6 hours on defined train routes per day)]
Heart rate variability is measured with the EndoPAT 2000 device during baseline recording. It includes time domain measures (SDNN, pNN50 and RMSSD), high (HF) and low frequency (LF) components as well as LF/HF ratio, based on measurements over 5 minutes.
DNA damage in peripheral blood mononuclear cells [Blood is sampled, prepared and stored after each exposure scenario (on the third day after 6 hours on defined train routes per day). Analysis is performed after sample collection completion.]
The levels of strand breaks and formamidopyrimidine-DNA-glycosylase (FPG) sites are measured with the single cell gel electrophoresis assay (comet assay) [7-13]

Secondary Outcome Measures

Lung function [The lung function is assessed after each exposure scenario (on the third day after 6 hours on defined train routes per day)]
The lung function is measured with EasyOne 2001 spirometer device (Switzerland). Lung function measurements includes forced vital capacity (FVC), forced expiratory volume after 1 second (FEV1), peak expiratory flow (PEF) and FEV1/FVC.
Systemic inflammatory markers [Blood is sampled, prepared and stored after each exposure scenario (on the third day after 6 hours on defined train routes per day). Analysis is performed after sample collection completion.]
Acute phase reactants, pro-inflammatory cytokines and cell adhesion molecules
Urinary excretion of 1-hydroxypyrene [Morning urine is sampled, prepared and stored after each exposure scenario (on the morning of the third day after two days with 6 hours on defined train routes). Analysis is performed after sample collection completion.]
The urinary biomarker of exposure to polycyclic aromatic hydrocarbons, 1-hydroxypyrene, is measured with reverse-phase HPLC and standardized for diuresis with the concentration of creatinine
Serum/plasma bioactivity [Blood is sampled, prepared and serum is stored after each exposure scenario (on the third day after 6 hours on defined train routes per day). Analysis is performed after sample collection completion.]
To assess the potential effects on vascular and endothelial function [14, 15]

Other Outcome Measures

Augmentation index [Assessed after each exposure scenario (on the third day after 6 hours on defined train routes per day)]
Measured with the EndoPAT 2000 device during baseline recording.
Blood pressure [Assessed after each exposure scenario (on the third day after 6 hours on defined train routes per day)]
Measured with an aneroid sphygmomanometer.
Heart rate [Assessed after each exposure scenario (on the third day after 6 hours on defined train routes per day)]
Measured with the EndoPAT 2000 device during baseline recording.