Combustion Derived Air Pollution and Vascular Function

This study has been completed.
Sponsor:
Collaborator:
National Institute for Public Health and the Environment (RIVM)
Information provided by:
University of Edinburgh
ClinicalTrials.gov Identifier:
NCT00775099
First received: October 16, 2008
Last updated: NA
Last verified: October 2008
History: No changes posted
  Purpose

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.

Condition Intervention
Endothelial Dysfunction
Procedure: Forearm Vascular Study
Procedure: Badimon Chamber

Study Type: Interventional
Study Design: Allocation: Randomized
Intervention Model: Crossover Assignment
Masking: Double Blind (Subject, Investigator, Outcomes Assessor)
Primary Purpose: Basic Science
Official Title: The Effects of Combustion-Derived Air Pollution on Vascular Vasomotor and Fibrinolytic Function in Healthy Volunteers (Diesel Exposure)

Resource links provided by NLM:


Further study details as provided by University of Edinburgh:

Primary Outcome Measures:
  • Forearm blood flow measured by forearm venous occlusion plethysmography in response to infused vasodilators [ Time Frame: 6-8 hours after exposure ] [ Designated as safety issue: No ]

Secondary Outcome Measures:
  • Ex-vivo thrombus formation assessed using the Badimon chamber [ Time Frame: 6 hours after exposure ] [ Designated as safety issue: No ]
  • Arterial stiffness measured by radial artery tonometry [ Time Frame: Before and after exposure ] [ Designated as safety issue: No ]
  • Heart rate and heart rate variability measured with 3 lead Holter electrographic monitors [ Time Frame: During and for 24 hours after exposure ] [ Designated as safety issue: No ]
  • Blood pressure [ Time Frame: During and after exposure and during forearm study ] [ Designated as safety issue: No ]
  • Plasma t-PA and PAI concentrations following infusion of bradykinin [ Time Frame: During forearm study ] [ Designated as safety issue: No ]
  • Plasma inflammatory markers IL-6, TNF-alpha, IL-1 and hsCRP [ Time Frame: Before and after exposure ] [ Designated as safety issue: No ]
  • Platelet monocyte binding as measured by flow cytometry [ Time Frame: After the exposure ] [ Designated as safety issue: No ]

Enrollment: 16
Study Start Date: September 2005
Study Completion Date: March 2006
Primary Completion Date: March 2006 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: Filtered Air Exposure
1 hour exposure to filtered air during intermittent exercise
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).
Other Names:
  • BK
  • SNP
  • ACh
Procedure: Badimon Chamber
Ex-vivo assessment of thrombus formation using Badimon Chamber
Experimental: Diesel Exhaust Exposure
1 hour exposure to dilute diesel exhaust at a concentration of 300 µg/m3 during intermittent exercise
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).
Other Names:
  • BK
  • SNP
  • ACh
Procedure: Badimon Chamber
Ex-vivo assessment of thrombus formation using Badimon Chamber
Experimental: Filtered Diesel Exposure
1 hour exposure to diesel exhaust with all particulates filtered out using teflon filter with intermittent exercise
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).
Other Names:
  • BK
  • SNP
  • ACh
Procedure: Badimon Chamber
Ex-vivo assessment of thrombus formation using Badimon Chamber
Experimental: PALAS Exposure
1 hour exposure to pure carbon particles produced by PALAS generator during intermittent exercise
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).
Other Names:
  • BK
  • SNP
  • ACh
Procedure: Badimon Chamber
Ex-vivo assessment of thrombus formation using Badimon Chamber

  Eligibility

Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   Yes
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
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT00775099

Locations
United Kingdom
University of Edinburgh
Edinburgh, United Kingdom, EH16 4SB
Sponsors and Collaborators
University of Edinburgh
National Institute for Public Health and the Environment (RIVM)
Investigators
Principal Investigator: Nicholas L Mills, MB BCh MRCP University of Edinburgh
  More Information

Publications:
Responsible Party: Professor David E Newby, University of Edinburgh
ClinicalTrials.gov Identifier: NCT00775099     History of Changes
Other Study ID Numbers: 05/S1103/46
Study First Received: October 16, 2008
Last Updated: October 16, 2008
Health Authority: United Kingdom: Research Ethics Committee

Keywords provided by University of Edinburgh:
Air Pollution
Particles
Particulate Matter
Vascular function
Endothelial function
Thrombosis

ClinicalTrials.gov processed this record on August 01, 2014