- ICH GCP
- Registro de ensaios clínicos dos EUA
- Ensaio Clínico 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.
Visão geral do estudo
Status
Condições
Intervenção / Tratamento
Tipo de estudo
Inscrição (Real)
Estágio
- Não aplicável
Contactos e Locais
Locais de estudo
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Edinburgh, Reino Unido, EH16 4SB
- University of Edinburgh
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Critérios de participação
Critérios de elegibilidade
Idades elegíveis para estudo
- Filho
- Adulto
- Adulto mais velho
Aceita Voluntários Saudáveis
Gêneros Elegíveis para o Estudo
Descrição
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
Plano de estudo
Como o estudo é projetado?
Detalhes do projeto
- Finalidade Principal: Ciência básica
- Alocação: Randomizado
- Modelo Intervencional: Atribuição cruzada
- Mascaramento: Triplo
Armas e Intervenções
Grupo de Participantes / Braço |
Intervenção / Tratamento |
|---|---|
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Experimental: Filtered Air Exposure
1 hour exposure to filtered air during intermittent exercise
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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).
Outros nomes:
Ex-vivo assessment of thrombus formation using Badimon Chamber
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Experimental: Diesel Exhaust Exposure
1 hour exposure to dilute diesel exhaust at a concentration of 300 µg/m3 during intermittent exercise
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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).
Outros nomes:
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
|
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).
Outros nomes:
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
|
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).
Outros nomes:
Ex-vivo assessment of thrombus formation using Badimon Chamber
|
O que o estudo está medindo?
Medidas de resultados primários
Medida de resultado |
Prazo |
|---|---|
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Forearm blood flow measured by forearm venous occlusion plethysmography in response to infused vasodilators
Prazo: 6-8 hours after exposure
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6-8 hours after exposure
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Medidas de resultados secundários
Medida de resultado |
Prazo |
|---|---|
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Ex-vivo thrombus formation assessed using the Badimon chamber
Prazo: 6 hours after exposure
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6 hours after exposure
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Arterial stiffness measured by radial artery tonometry
Prazo: Before and after exposure
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Before and after exposure
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Heart rate and heart rate variability measured with 3 lead Holter electrographic monitors
Prazo: During and for 24 hours after exposure
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During and for 24 hours after exposure
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Blood pressure
Prazo: During and after exposure and during forearm study
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During and after exposure and during forearm study
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Plasma t-PA and PAI concentrations following infusion of bradykinin
Prazo: During forearm study
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During forearm study
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Plasma inflammatory markers IL-6, TNF-alpha, IL-1 and hsCRP
Prazo: Before and after exposure
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Before and after exposure
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Platelet monocyte binding as measured by flow cytometry
Prazo: After the exposure
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After the exposure
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Colaboradores e Investigadores
Patrocinador
Investigadores
- Investigador principal: Nicholas L Mills, MB BCh MRCP, University of Edinburgh
Publicações e links úteis
Publicações Gerais
- 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.
Datas de registro do estudo
Datas Principais do Estudo
Início do estudo
Conclusão Primária (Real)
Conclusão do estudo (Real)
Datas de inscrição no estudo
Enviado pela primeira vez
Enviado pela primeira vez que atendeu aos critérios de CQ
Primeira postagem (Estimativa)
Atualizações de registro de estudo
Última Atualização Postada (Estimativa)
Última atualização enviada que atendeu aos critérios de controle de qualidade
Última verificação
Mais Informações
Termos relacionados a este estudo
Palavras-chave
Outros números de identificação do estudo
- 05/S1103/46
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