- ICH GCP
- US Clinical Trials Registry
- Klinisk forsøg NCT00775099
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)
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:
- Combustion derived nanoparticulate causes an acute impairment of endothelial vasomotor and fibrinolytic function in healthy volunteers.
- Exposure to combustion derived air pollution is associated with increased thrombus formation.
Studieoversigt
Status
Betingelser
Intervention / Behandling
Undersøgelsestype
Tilmelding (Faktiske)
Fase
- Ikke anvendelig
Kontakter og lokationer
Studiesteder
-
-
-
Edinburgh, Det Forenede Kongerige, EH16 4SB
- University of Edinburgh
-
-
Deltagelseskriterier
Berettigelseskriterier
Aldre berettiget til at studere
- Barn
- Voksen
- Ældre voksen
Tager imod sunde frivillige
Køn, der er berettiget til at studere
Beskrivelse
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
Studieplan
Hvordan er undersøgelsen tilrettelagt?
Design detaljer
- Primært formål: Grundvidenskab
- Tildeling: Randomiseret
- Interventionel model: Crossover opgave
- Maskning: Tredobbelt
Våben og indgreb
Deltagergruppe / Arm |
Intervention / Behandling |
---|---|
Eksperimentel: Filtered Air Exposure
1 hour exposure to filtered air during intermittent exercise
|
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).
Andre navne:
Ex-vivo assessment of thrombus formation using Badimon Chamber
|
Eksperimentel: Diesel Exhaust Exposure
1 hour exposure to dilute diesel exhaust at a concentration of 300 µg/m3 during intermittent exercise
|
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).
Andre navne:
Ex-vivo assessment of thrombus formation using Badimon Chamber
|
Eksperimentel: Filtered Diesel Exposure
1 hour exposure to diesel exhaust with all particulates filtered out using teflon filter with intermittent exercise
|
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).
Andre navne:
Ex-vivo assessment of thrombus formation using Badimon Chamber
|
Eksperimentel: PALAS Exposure
1 hour exposure to pure carbon particles produced by PALAS generator during intermittent exercise
|
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).
Andre navne:
Ex-vivo assessment of thrombus formation using Badimon Chamber
|
Hvad måler undersøgelsen?
Primære resultatmål
Resultatmål |
Tidsramme |
---|---|
Forearm blood flow measured by forearm venous occlusion plethysmography in response to infused vasodilators
Tidsramme: 6-8 hours after exposure
|
6-8 hours after exposure
|
Sekundære resultatmål
Resultatmål |
Tidsramme |
---|---|
Ex-vivo thrombus formation assessed using the Badimon chamber
Tidsramme: 6 hours after exposure
|
6 hours after exposure
|
Arterial stiffness measured by radial artery tonometry
Tidsramme: Before and after exposure
|
Before and after exposure
|
Heart rate and heart rate variability measured with 3 lead Holter electrographic monitors
Tidsramme: During and for 24 hours after exposure
|
During and for 24 hours after exposure
|
Blood pressure
Tidsramme: During and after exposure and during forearm study
|
During and after exposure and during forearm study
|
Plasma t-PA and PAI concentrations following infusion of bradykinin
Tidsramme: During forearm study
|
During forearm study
|
Plasma inflammatory markers IL-6, TNF-alpha, IL-1 and hsCRP
Tidsramme: Before and after exposure
|
Before and after exposure
|
Platelet monocyte binding as measured by flow cytometry
Tidsramme: After the exposure
|
After the exposure
|
Samarbejdspartnere og efterforskere
Sponsor
Samarbejdspartnere
Efterforskere
- Ledende efterforsker: Nicholas L Mills, MB BCh MRCP, University of Edinburgh
Publikationer og nyttige links
Generelle publikationer
- 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.
- 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.
Datoer for undersøgelser
Studer store datoer
Studiestart
Primær færdiggørelse (Faktiske)
Studieafslutning (Faktiske)
Datoer for studieregistrering
Først indsendt
Først indsendt, der opfyldte QC-kriterier
Først opslået (Skøn)
Opdateringer af undersøgelsesjournaler
Sidste opdatering sendt (Skøn)
Sidste opdatering indsendt, der opfyldte kvalitetskontrolkriterier
Sidst verificeret
Mere information
Begreber relateret til denne undersøgelse
Andre undersøgelses-id-numre
- 05/S1103/46
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