Clinical trial NCT00775099: Combustion Derived Air Pollution and Vascular Function
Official title: The Effects of Combustion-Derived Air Pollution on Vascular Vasomotor and Fibrinolytic Function in Healthy Volunteers (Diesel Exposure)
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: NA
Conditions: Endothelial Dysfunction
Keywords: Air Pollution
Particles
Particulate Matter
Vascular function
Endothelial function
Thrombosis
Lead sponsor: University of Edinburgh
Sponsor class: OTHER
Collaborators: name: National Institute for Public Health and the Environment (RIVM)
First posted: 2008-10-17
Enrollment: 16
Sex: ALL
Standard ages: CHILD
ADULT
OLDER_ADULT
Accepts healthy volunteers: yes
Allocation: RANDOMIZED
Intervention model: CROSSOVER
Primary purpose: BASIC_SCIENCE

Brief summary: Air pollution is a major cause of cardiovascular morbidity and mortality. The components of air pollution responsible and the mechanisms through which they might mediate these harmful effects remain only partially understood. The link between cardiovascular disease and air pollution is strongest for fine particulate matter. Fine particulate matter (PM) is produced from the combustion of fossil fuels with the most significant threat thought to be posed by small particles less than 10µm (PM 10) which can be inhaled into the lungs. We propose to identify the precise component of diesel exhaust that mediates the adverse cardiovascular effects using a carbon particle generator, and a particle concentrator. The aim of this study proposal is to assess the vascular effects of different types and components of air pollution in healthy subjects. We intend to test the hypotheses that:

1. Combustion derived nanoparticulate causes an acute impairment of endothelial vasomotor and fibrinolytic function in healthy volunteers.
2. Exposure to combustion derived air pollution is associated with increased thrombus formation.


Eligibility criteria: Inclusion Criteria:

* Healthy volunteers

Exclusion Criteria:

* Current smokers
* Significant occupational exposure to air pollution
* History of lung disease
* Women of child-bearing potential
* Malignant arrhythmias
* Renal or hepatic failure
* Significant co-morbidity
* Systolic blood pressure \>190 or \<100 mmHg
* Previous history of blood dyscrasia
* Unable to tolerate the supine position
* Lack of informed consent
* Blood donation within last 3 months

Primary outcomes:
measure: Forearm blood flow measured by forearm venous occlusion plethysmography in response to infused vasodilators
timeFrame: 6-8 hours after exposure
Secondary outcomes:
measure: Ex-vivo thrombus formation assessed using the Badimon chamber
timeFrame: 6 hours after exposure
measure: Arterial stiffness measured by radial artery tonometry
timeFrame: Before and after exposure
measure: Heart rate and heart rate variability measured with 3 lead Holter electrographic monitors
timeFrame: During and for 24 hours after exposure
measure: Blood pressure
timeFrame: During and after exposure and during forearm study
measure: Plasma t-PA and PAI concentrations following infusion of bradykinin
timeFrame: During forearm study
measure: Plasma inflammatory markers IL-6, TNF-alpha, IL-1 and hsCRP
timeFrame: Before and after exposure
measure: Platelet monocyte binding as measured by flow cytometry
timeFrame: After the exposure
Other outcomes:
Locations:
city: Edinburgh
country: United Kingdom
facility: University of Edinburgh
Study officials:
affiliation: University of Edinburgh
name: Nicholas L Mills, MB BCh MRCP
role: PRINCIPAL_INVESTIGATOR
References:
citation: Mills NL, Tornqvist H, Robinson SD, Gonzalez M, Darnley K, MacNee W, Boon NA, Donaldson K, Blomberg A, Sandstrom T, Newby DE. Diesel exhaust inhalation causes vascular dysfunction and impaired endogenous fibrinolysis. Circulation. 2005 Dec 20;112(25):3930-6. doi: 10.1161/CIRCULATIONAHA.105.588962.
citation: Langrish JP, Watts SJ, Hunter AJ, Shah AS, Bosson JA, Unosson J, Barath S, Lundback M, Cassee FR, Donaldson K, Sandstrom T, Blomberg A, Newby DE, Mills NL. Controlled exposures to air pollutants and risk of cardiac arrhythmia. Environ Health Perspect. 2014 Jul;122(7):747-53. doi: 10.1289/ehp.1307337. Epub 2014 Mar 25.