Combustion Derived Air Pollution and Vascular Function
The Effects of Combustion-Derived Air Pollution on Vascular Vasomotor and Fibrinolytic Function in Healthy Volunteers (Diesel Exposure)
1 other identifier
interventional
16
1 country
1
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.
Trial Health
Trial Health Score
Automated assessment based on enrollment pace, timeline, and geographic reach
participants targeted
Target at below P25 for not_applicable
Started Sep 2005
Shorter than P25 for not_applicable
1 active site
Health score is calculated from publicly available data and should be used for screening purposes only.
Trial Relationships
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Study Timeline
Key milestones and dates
Study Start
First participant enrolled
September 1, 2005
CompletedPrimary Completion
Last participant's last visit for primary outcome
March 1, 2006
CompletedStudy Completion
Last participant's last visit for all outcomes
March 1, 2006
CompletedFirst Submitted
Initial submission to the registry
October 16, 2008
CompletedFirst Posted
Study publicly available on registry
October 17, 2008
CompletedOctober 17, 2008
October 1, 2008
6 months
October 16, 2008
October 16, 2008
Conditions
Keywords
Outcome Measures
Primary Outcomes (1)
Forearm blood flow measured by forearm venous occlusion plethysmography in response to infused vasodilators
6-8 hours after exposure
Secondary Outcomes (7)
Ex-vivo thrombus formation assessed using the Badimon chamber
6 hours after exposure
Arterial stiffness measured by radial artery tonometry
Before and after exposure
Heart rate and heart rate variability measured with 3 lead Holter electrographic monitors
During and for 24 hours after exposure
Blood pressure
During and after exposure and during forearm study
Plasma t-PA and PAI concentrations following infusion of bradykinin
During forearm study
- +2 more secondary outcomes
Study Arms (4)
Filtered Air Exposure
EXPERIMENTAL1 hour exposure to filtered air during intermittent exercise
Diesel Exhaust Exposure
EXPERIMENTAL1 hour exposure to dilute diesel exhaust at a concentration of 300 µg/m3 during intermittent exercise
Filtered Diesel Exposure
EXPERIMENTAL1 hour exposure to diesel exhaust with all particulates filtered out using teflon filter with intermittent exercise
PALAS Exposure
EXPERIMENTAL1 hour exposure to pure carbon particles produced by PALAS generator during intermittent exercise
Interventions
Forearm venous occlusion plethysmography to measure forearm blood flow during intra-arterial infusion of the vasodilators Verapamil (10-100 µg/min), bradykinin (100-1000 pmol/min), sodium nitroprusside (2-8 µg/min) and Acetylcholine (5-20 mg/min).
Ex-vivo assessment of thrombus formation using Badimon Chamber
Eligibility Criteria
You may qualify if:
- Healthy volunteers
You may not qualify if:
- 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
Contact the study team to confirm eligibility.
Sponsors & Collaborators
Study Sites (1)
University of Edinburgh
Edinburgh, EH16 4SB, United Kingdom
Related Publications (2)
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.
PMID: 16365212BACKGROUNDLangrish 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.
PMID: 24667535DERIVED
MeSH Terms
Conditions
Condition Hierarchy (Ancestors)
Study Officials
- PRINCIPAL INVESTIGATOR
Nicholas L Mills, MB BCh MRCP
University of Edinburgh
Study Design
- Study Type
- interventional
- Phase
- not applicable
- Allocation
- RANDOMIZED
- Masking
- TRIPLE
- Who Masked
- PARTICIPANT, INVESTIGATOR, OUTCOMES ASSESSOR
- Purpose
- BASIC SCIENCE
- Intervention Model
- CROSSOVER
- Sponsor Type
- OTHER
Study Record Dates
First Submitted
October 16, 2008
First Posted
October 17, 2008
Study Start
September 1, 2005
Primary Completion
March 1, 2006
Study Completion
March 1, 2006
Last Updated
October 17, 2008
Record last verified: 2008-10