Combustion Derived Air Pollution and Vascular Function

Endothelial Dysfunction Clinical Trial

Official title:

The Effects of Combustion-Derived Air Pollution on Vascular Vasomotor and Fibrinolytic Function in Healthy Volunteers (Diesel Exposure)

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT00775099
• Other study ID #: 05/S1103/46
• Status: Completed
• Phase: N/A
• First received: October 16, 2008
• Last updated: October 16, 2008
• Start date: September 2005
• Est. completion date: March 2006

Study information

• Verified date: October 2008
• Source: University of Edinburgh
• Contact: n/a
• Is FDA regulated: No
• Health authority: United Kingdom: Research Ethics Committee
• Study type: Interventional

Clinical Trial 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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 16
• Est. completion date: March 2006
• Est. primary completion date: March 2006
• Accepts healthy volunteers: Accepts Healthy Volunteers
• Gender: Both
• Age group: N/A and older

Eligibility

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

Study Design

Allocation: Randomized, Intervention Model: Crossover Assignment, Masking: Double Blind (Subject, Investigator, Outcomes Assessor), Primary Purpose: Basic Science

Related Conditions & MeSH terms

• Endothelial Dysfunction

Intervention

Procedure:
• Forearm Vascular Study
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).
• Badimon Chamber
Ex-vivo assessment of thrombus formation using Badimon Chamber

Locations

Country	Name	City	State
United Kingdom	University of Edinburgh	Edinburgh

Sponsors (2)

Lead Sponsor	Collaborator
University of Edinburgh	National Institute for Public Health and the Environment (RIVM)

Country where clinical trial is conducted

United Kingdom, 

References & Publications (1)

Mills NL, Törnqvist 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. — View Citation

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Forearm blood flow measured by forearm venous occlusion plethysmography in response to infused vasodilators		6-8 hours after exposure	No
Secondary	Ex-vivo thrombus formation assessed using the Badimon chamber		6 hours after exposure	No
Secondary	Arterial stiffness measured by radial artery tonometry		Before and after exposure	No
Secondary	Heart rate and heart rate variability measured with 3 lead Holter electrographic monitors		During and for 24 hours after exposure	No
Secondary	Blood pressure		During and after exposure and during forearm study	No
Secondary	Plasma t-PA and PAI concentrations following infusion of bradykinin		During forearm study	No
Secondary	Plasma inflammatory markers IL-6, TNF-alpha, IL-1 and hsCRP		Before and after exposure	No
Secondary	Platelet monocyte binding as measured by flow cytometry		After the exposure	No