Clinical trial NCT03104387: Health Effects of Occupational Exposure to Combustion Particles - a Study on Volunteers Performing as Train Conductors
Official title: Effects of Diesel Combustion Generated Air Pollution on Cardiovascular Function and Oxidatively Damaged DNA in Healthy Volunteers
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: NA
Conditions: Cardiovascular Function
Genotoxicity
Keywords: Air pollution
Diesel exhaust
Ultrafine particles
Vascular function
Endothelium function
Heart rate variability
DNA damage
Lead sponsor: University of Copenhagen
Sponsor class: OTHER
Collaborators: name: National Research Centre for the Working Environment, Denmark
First posted: 2017-04-07
Enrollment: 29
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: yes
Allocation: RANDOMIZED
Intervention model: CROSSOVER
Primary purpose: BASIC_SCIENCE

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.


Eligibility criteria: Inclusion Criteria:

* Healthy volunteers
* Legally competent subjects

Exclusion Criteria:

* Current smokers
* Pregnancy
* Alcohol and drug abuse
* Prescriptionary use of anti-inflammatory or cardiovascular medication

Primary outcomes:
measure: Reactive hyperemia index measured by peripheral arterial tonometry
timeFrame: Peripheral arterial tonometry is assessed after each exposure scenario (on the third day after 6 hours on defined train routes per day)
measure: Heart rate variability
timeFrame: Assessed after each exposure scenario (on the third day after 6 hours on defined train routes per day)
measure: DNA damage in peripheral blood mononuclear cells
timeFrame: 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 outcomes:
measure: Lung function
timeFrame: The lung function is assessed after each exposure scenario (on the third day after 6 hours on defined train routes per day)
measure: Systemic inflammatory markers
timeFrame: 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.
measure: Urinary excretion of 1-hydroxypyrene
timeFrame: 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.
measure: Serum/plasma bioactivity
timeFrame: 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.
Other outcomes:
measure: Augmentation index
timeFrame: Assessed after each exposure scenario (on the third day after 6 hours on defined train routes per day)
measure: Blood pressure
timeFrame: Assessed after each exposure scenario (on the third day after 6 hours on defined train routes per day)
measure: Heart rate
timeFrame: Assessed after each exposure scenario (on the third day after 6 hours on defined train routes per day)
Locations:
city: Copenhagen
country: Denmark
facility: University of Copenhagen
Study officials:
affiliation: University of Copenhagen
name: Peter Moller, PhD
role: PRINCIPAL_INVESTIGATOR
References:
citation: Karottki G, Loft S. Rapport vedroerende maaling af udsaettelse for ultrafine partikler blandt ansatte i DSB, 1-48, 2015.
citation: Brauner EV, Forchhammer L, Moller P, Barregard L, Gunnarsen L, Afshari A, Wahlin 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 Crit Care Med. 2008 Feb 15;177(4):419-25. doi: 10.1164/rccm.200704-632OC. Epub 2007 Oct 11.
citation: Olsen Y, Karottki DG, Jensen DM, Beko G, Kjeldsen BU, Clausen G, Hersoug LG, Holst GJ, Wierzbicka A, Sigsgaard T, Linneberg A, Moller P, Loft S. Vascular and lung function related to ultrafine and fine particles exposure assessed by personal and indoor monitoring: a cross-sectional study. Environ Health. 2014 Dec 15;13:112. doi: 10.1186/1476-069X-13-112.
citation: Karottki DG, Spilak M, Frederiksen M, Gunnarsen L, Brauner EV, Kolarik B, Andersen ZJ, Sigsgaard T, Barregard L, Strandberg B, Sallsten G, Moller P, Loft S. An indoor air filtration study in homes of elderly: cardiovascular and respiratory effects of exposure to particulate matter. Environ Health. 2013 Dec 28;12:116. doi: 10.1186/1476-069X-12-116.
citation: Hemmingsen JG, Rissler J, Lykkesfeldt J, Sallsten G, Kristiansen J, Moller 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. Part Fibre Toxicol. 2015 Mar 19;12:6. doi: 10.1186/s12989-015-0081-9.
citation: Brauner EV, Moller P, Barregard L, Dragsted LO, Glasius M, Wahlin 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 individuals. Part Fibre Toxicol. 2008 Oct 6;5:13. doi: 10.1186/1743-8977-5-13.
citation: Forchhammer L, Moller P, Riddervold IS, Bonlokke 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.
citation: Brauner EV, Forchhammer L, Moller P, Simonsen J, Glasius M, Wahlin 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. doi: 10.1289/ehp.9984.
citation: Danielsen PH, Brauner EV, Barregard L, Sallsten G, Wallin M, Olinski R, Rozalski R, Moller 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.mrfmmm.2008.04.001. Epub 2008 Apr 14.
citation: Hemmingsen JG, Jantzen K, Moller 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. Epub 2015 Apr 22.
citation: Moller 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. 2014 Oct-Dec;762:133-66. doi: 10.1016/j.mrrev.2014.09.001. Epub 2014 Sep 16.
citation: Moller 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 nanomaterials exposure. Mutagenesis. 2015 Jan;30(1):67-83. doi: 10.1093/mutage/geu035.
citation: Moller 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.
citation: 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 via the CD36 Scavenger Receptor. Toxicol Sci. 2016 Apr;150(2):488-98. doi: 10.1093/toxsci/kfw015. Epub 2016 Jan 21.
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.
citation: Andersen MHG, Frederiksen M, Saber AT, Wils RS, Fonseca AS, Koponen IK, Johannesson S, Roursgaard M, Loft S, Moller P, Vogel U. Health effects of exposure to diesel exhaust in diesel-powered trains. Part Fibre Toxicol. 2019 Jun 11;16(1):21. doi: 10.1186/s12989-019-0306-4.