The Effects of Diesel Exhaust Inhalation on Vascular Function - the Role of Endothelin

Not Applicable

Completed

• Conditions: Coronary Disease
• Interventions: Drug: BQ-123 and BQ-788; Drug: Endothelin-1

• Registration Number: NCT00745693
• Lead Sponsor: University of Edinburgh

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.

Study Timeline

• Study Start: 2008-03
• Primary Completion: 2008-05
• Study Completion: 2008-05
• Status Verified: 2008-09
• Study First Submitted: 2008-09-02
• Study First Submitted QC: 2008-09-02
• Study First Posted: 2008-09-03
• Last Update Submitted: 2024-05-15
• Last Update Posted: 2024-05-17

Recruitment & Eligibility

• Status: COMPLETED
• Sex: Male
• Target Recruitment: 15

Inclusion Criteria

• Healthy male volunteers

Exclusion Criteria

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

Study & Design

• Study Type: INTERVENTIONAL
• Study Design: CROSSOVER

Arm && Interventions

Group	Intervention	Description
4	BQ-123 and BQ-788	1 hour exposure to dilute diesel exhaust (300mcg/m3), followed by forearm venous occlusion plethysmography at 2 hours after the exposure and infusion of endothelin receptor antagonists BQ-123 and BQ-788
2	BQ-123 and BQ-788	1 hour exposure to filtered air, followed by forearm venous occlusion plethysmography at 2 hours after the exposure and infusion of endothelin receptor antagonists BQ-123 and BQ-788
1	Endothelin-1	1 hour exposure to filtered air, followed by forearm venous occlusion plethysmography at 2 hours after the exposure and infusion of endothelin-1 (5pmol/min)
3	Endothelin-1	1 hour exposure to dilute diesel exhaust (300mcg/m3), followed by forearm venous occlusion plethysmography at 2 hours after the exposure and infusion of endothelin-1 (5pmol/min)

Primary Outcome Measures

Name	Time	Method
Change in forearm blood flow following infusion of endothelin-1 or the endothelin receptor antagonists BQ-123 & BQ-788	2 hours after exposure

Secondary Outcome Measures

Name	Time	Method
24 hour mean blood pressure (ambulatory monitoring)	24 hours following the exposure
Systemic endothelin-1 and big endothelin-1 concentrations	At baseline, and immediately, 1, 2, 3, 4, 6 and 24 hours after exposure
Changes in arterial stiffness (pulse-wave velocity)	During and for the 1 hour after the exposure

Trial Locations

Locations (1)

Umeå University; 🇸🇪 Umeå, Västerbottens, Sweden