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

Genotoxicity Clinical Trial

— BioTrack  

Official title:

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

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT03104387
• Other study ID #: H-16033227
• Secondary ID: No grant number2
• Status: Completed
• Phase: N/A
• Start date: May 16, 2017
• Est. completion date: May 1, 2020

Study information

• Verified date: August 2020
• Source: University of Copenhagen
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 29
• Est. completion date: May 1, 2020
• Est. primary completion date: September 30, 2018
• Accepts healthy volunteers: Accepts Healthy Volunteers
• Gender: All
• Age group: 18 Years and older

Eligibility

Inclusion Criteria:

• Healthy volunteers

• Legally competent subjects

Exclusion Criteria:

• Current smokers

• Pregnancy

• Alcohol and drug abuse

• Prescriptionary use of anti-inflammatory or cardiovascular medication

Related Conditions & MeSH terms

• Cardiovascular Function
• Genotoxicity

Intervention

Other:
• Electric train
Exposure to air with low level of ultrafine particles (Electric train)
• Diesel train
Exposure to air with high level of ultrafine particles (Diesel train)

Locations

Country	Name	City	State
Denmark	University of Copenhagen	Copenhagen

Sponsors (2)

Lead Sponsor	Collaborator
University of Copenhagen	National Research Centre for the Working Environment, Denmark

Country where clinical trial is conducted

Denmark, 

References & Publications (15)

Aragon M, Erdely A, Bishop L, Salmen R, Weaver J, Liu J, Hall P, Eye T, Kodali V, Zeidler-Erdely P, Stafflinger JE, Ottens AK, Campen MJ. MMP-9-Dependent Serum-Borne Bioactivity Caused by Multiwalled Carbon Nanotube Exposure Induces Vascular Dysfunction v — View Citation

Aragon MJ, Chrobak I, Brower J, Roldan L, Fredenburgh LE, McDonald JD, Campen MJ. Inflammatory and Vasoactive Effects of Serum Following Inhalation of Varied Complex Mixtures. Cardiovasc Toxicol. 2016 Apr;16(2):163-71. doi: 10.1007/s12012-015-9325-z. — View Citation

Bräuner EV, Forchhammer L, Møller P, Barregard L, Gunnarsen L, Afshari A, Wåhlin P, Glasius M, Dragsted LO, Basu S, Raaschou-Nielsen O, Loft S. Indoor particles affect vascular function in the aged: an air filtration-based intervention study. Am J Respir — View Citation

Bräuner EV, Forchhammer L, Møller P, Simonsen J, Glasius M, Wåhlin P, Raaschou-Nielsen O, Loft S. Exposure to ultrafine particles from ambient air and oxidative stress-induced DNA damage. Environ Health Perspect. 2007 Aug;115(8):1177-82. — View Citation

Bräuner EV, Møller P, Barregard L, Dragsted LO, Glasius M, Wåhlin P, Vinzents P, Raaschou-Nielsen O, Loft S. Exposure to ambient concentrations of particulate air pollution does not influence vascular function or inflammatory pathways in young healthy ind — View Citation

Danielsen PH, Bräuner EV, Barregard L, Sällsten G, Wallin M, Olinski R, Rozalski R, Møller P, Loft S. Oxidatively damaged DNA and its repair after experimental exposure to wood smoke in healthy humans. Mutat Res. 2008 Jul 3;642(1-2):37-42. doi: 10.1016/j. — View Citation

Forchhammer L, Møller P, Riddervold IS, Bønløkke J, Massling A, Sigsgaard T, Loft S. Controlled human wood smoke exposure: oxidative stress, inflammation and microvascular function. Part Fibre Toxicol. 2012 Mar 27;9:7. doi: 10.1186/1743-8977-9-7. — View Citation

Hemmingsen JG, Jantzen K, Møller P, Loft S. No oxidative stress or DNA damage in peripheral blood mononuclear cells after exposure to particles from urban street air in overweight elderly. Mutagenesis. 2015 Sep;30(5):635-42. doi: 10.1093/mutage/gev027. Ep — View Citation

Hemmingsen JG, Rissler J, Lykkesfeldt J, Sallsten G, Kristiansen J, Møller P P, Loft S. Controlled exposure to particulate matter from urban street air is associated with decreased vasodilation and heart rate variability in overweight and older adults. Pa — View Citation

Karottki DG, Spilak M, Frederiksen M, Gunnarsen L, Brauner EV, Kolarik B, Andersen ZJ, Sigsgaard T, Barregard L, Strandberg B, Sallsten G, Møller P, Loft S. An indoor air filtration study in homes of elderly: cardiovascular and respiratory effects of expo — View Citation

Karottki G, Loft S. Rapport vedroerende maaling af udsaettelse for ultrafine partikler blandt ansatte i DSB, 1-48, 2015.

Møller P, Danielsen PH, Karottki DG, Jantzen K, Roursgaard M, Klingberg H, Jensen DM, Christophersen DV, Hemmingsen JG, Cao Y, Loft S. Oxidative stress and inflammation generated DNA damage by exposure to air pollution particles. Mutat Res Rev Mutat Res. — View Citation

Møller P, Hemmingsen JG, Jensen DM, Danielsen PH, Karottki DG, Jantzen K, Roursgaard M, Cao Y, Kermanizadeh A, Klingberg H, Christophersen DV, Hersoug LG, Loft S. Applications of the comet assay in particle toxicology: air pollution and engineered nanomat — View Citation

Møller P, Loft S. Oxidative damage to DNA and lipids as biomarkers of exposure to air pollution. Environ Health Perspect. 2010 Aug;118(8):1126-36. doi: 10.1289/ehp.0901725. Epub 2010 Apr 27. Review. — View Citation

Olsen Y, Karottki DG, Jensen DM, Bekö G, Kjeldsen BU, Clausen G, Hersoug LG, Holst GJ, Wierzbicka A, Sigsgaard T, Linneberg A, Møller P, Loft S. Vascular and lung function related to ultrafine and fine particles exposure assessed by personal and indoor mo — View Citation

* Note: There are 15 references in all — Click here to view all references

Outcome

Type	Measure	Description	Time frame	Safety issue
Other	Augmentation index	Measured with the EndoPAT 2000 device during baseline recording.	Assessed after each exposure scenario (on the third day after 6 hours on defined train routes per day)
Other	Blood pressure	Measured with an aneroid sphygmomanometer.	Assessed after each exposure scenario (on the third day after 6 hours on defined train routes per day)
Other	Heart rate	Measured with the EndoPAT 2000 device during baseline recording.	Assessed after each exposure scenario (on the third day after 6 hours on defined train routes per day)
Primary	Reactive hyperemia index measured by peripheral arterial tonometry	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].	Peripheral arterial tonometry is assessed after each exposure scenario (on the third day after 6 hours on defined train routes per day)
Primary	Heart rate variability	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.	Assessed after each exposure scenario (on the third day after 6 hours on defined train routes per day)
Primary	DNA damage in peripheral blood mononuclear cells	The levels of strand breaks and formamidopyrimidine-DNA-glycosylase (FPG) sites are measured with the single cell gel electrophoresis assay (comet assay) [7-13]	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.
Secondary	Lung function	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.	The lung function is assessed after each exposure scenario (on the third day after 6 hours on defined train routes per day)
Secondary	Systemic inflammatory markers	Acute phase reactants, pro-inflammatory cytokines and cell adhesion molecules	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.
Secondary	Urinary excretion of 1-hydroxypyrene	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	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.
Secondary	Serum/plasma bioactivity	To assess the potential effects on vascular and endothelial function [14, 15]	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.