Clinical trial NCT00745693: The Effects of Diesel Exhaust Inhalation on Vascular Function - the Role of Endothelin
Official title: The Effects of Diesel Exhaust Inhalation on Vascular Function - the Role of Endothelin
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: NA
Conditions: Coronary Disease
Keywords: Endothelin
Air pollution
Diesel exhaust
Vascular function
exposure
Lead sponsor: University of Edinburgh
Sponsor class: OTHER
Collaborators: name: Umeå University
First posted: 2008-09-03
Enrollment: 15
Sex: MALE
Minimum age (years): 18
Maximum age (years): 35
Standard ages: ADULT
Accepts healthy volunteers: yes
Allocation: RANDOMIZED
Intervention model: CROSSOVER
Primary purpose: BASIC_SCIENCE

Brief summary: The purpose of this study is to identify the role of endothelin 1 (a natural vasoconstrictor) in the adverse vascular effects demonstrated after exposure to air pollution

Detailed description: Air pollution is a major problem, and can be linked to around 5% of all deaths worldwide each year. There are strong associations between air pollution exposure and heart disease but we do not yet understand how these harmful effects are mediated. Understanding this mechanism is likely to have a major impact on the way we treat patients with heart disease and have the potential to shape future environmental health policy. The upregulation of Endothelin-1 provides a plausible mechanism for these harmful effects, and we plan to investigate this in more depth in the human forearm following exposure to diesel exhaust.

Eligibility criteria: Inclusion Criteria:

* Healthy male volunteers

Exclusion Criteria:

* Use of regular medication
* Cigarette smoking
* Significant occupational exposure to air pollution
* Intercurrent illness

Primary outcomes:
measure: Change in forearm blood flow following infusion of endothelin-1 or the endothelin receptor antagonists BQ-123 & BQ-788
timeFrame: 2 hours after exposure
Secondary outcomes:
measure: 24 hour mean blood pressure (ambulatory monitoring)
timeFrame: 24 hours following the exposure
measure: Systemic endothelin-1 and big endothelin-1 concentrations
timeFrame: At baseline, and immediately, 1, 2, 3, 4, 6 and 24 hours after exposure
measure: Changes in arterial stiffness (pulse-wave velocity)
timeFrame: During and for the 1 hour after the exposure
Other outcomes:
Locations:
city: Umeå
country: Sweden
facility: Umeå University
state: Västerbottens
Study officials:
affiliation: University of Edinburgh
name: Jeremy P Langrish, MB BCh MRCP
role: PRINCIPAL_INVESTIGATOR
affiliation: Umeå University
name: Anders Blomberg, MD
role: STUDY_DIRECTOR
affiliation: Umeå University
name: Thomas Sandström, MD
role: STUDY_DIRECTOR
affiliation: University of Edinburgh
name: David E Newby, MD FRCP
role: STUDY_DIRECTOR
References:
citation: 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.
citation: Tornqvist H, Mills NL, Gonzalez M, Miller MR, Robinson SD, Megson IL, Macnee W, Donaldson K, Soderberg S, Newby DE, Sandstrom T, Blomberg A. Persistent endothelial dysfunction in humans after diesel exhaust inhalation. Am J Respir Crit Care Med. 2007 Aug 15;176(4):395-400. doi: 10.1164/rccm.200606-872OC. Epub 2007 Apr 19.
citation: Calderon-Garciduenas L, Vincent R, Mora-Tiscareno A, Franco-Lira M, Henriquez-Roldan C, Barragan-Mejia G, Garrido-Garcia L, Camacho-Reyes L, Valencia-Salazar G, Paredes R, Romero L, Osnaya H, Villarreal-Calderon R, Torres-Jardon R, Hazucha MJ, Reed W. Elevated plasma endothelin-1 and pulmonary arterial pressure in children exposed to air pollution. Environ Health Perspect. 2007 Aug;115(8):1248-53. doi: 10.1289/ehp.9641.
citation: Peretz A, Sullivan JH, Leotta DF, Trenga CA, Sands FN, Allen J, Carlsten C, Wilkinson CW, Gill EA, Kaufman JD. Diesel exhaust inhalation elicits acute vasoconstriction in vivo. Environ Health Perspect. 2008 Jul;116(7):937-42. doi: 10.1289/ehp.11027.
citation: Vincent R, Kumarathasan P, Goegan P, Bjarnason SG, Guenette J, Berube D, Adamson IY, Desjardins S, Burnett RT, Miller FJ, Battistini B. Inhalation toxicology of urban ambient particulate matter: acute cardiovascular effects in rats. Res Rep Health Eff Inst. 2001 Oct;(104):5-54; discussion 55-62.
citation: Langrish JP, Lundback M, Mills NL, Johnston NR, Webb DJ, Sandstrom T, Blomberg A, Newby DE. Contribution of endothelin 1 to the vascular effects of diesel exhaust inhalation in humans. Hypertension. 2009 Oct;54(4):910-5. doi: 10.1161/HYPERTENSIONAHA.109.135947. Epub 2009 Aug 17.