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

This study has been completed.
Sponsor:
Collaborator:
Umeå University
Information provided by:
University of Edinburgh
ClinicalTrials.gov Identifier:
NCT00745693
First received: September 2, 2008
Last updated: September 4, 2008
Last verified: September 2008
  Purpose

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


Condition Intervention
Coronary Disease
Drug: Endothelin-1
Drug: BQ-123 and BQ-788

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 Diesel Exhaust Inhalation on Vascular Function - the Role of Endothelin

Resource links provided by NLM:


Further study details as provided by University of Edinburgh:

Primary Outcome Measures:
  • Change in forearm blood flow following infusion of endothelin-1 or the endothelin receptor antagonists BQ-123 & BQ-788 [ Time Frame: 2 hours after exposure ] [ Designated as safety issue: No ]

Secondary Outcome Measures:
  • 24 hour mean blood pressure (ambulatory monitoring) [ Time Frame: 24 hours following the exposure ] [ Designated as safety issue: No ]
  • Systemic endothelin-1 and big endothelin-1 concentrations [ Time Frame: At baseline, and immediately, 1, 2, 3, 4, 6 and 24 hours after exposure ] [ Designated as safety issue: No ]
  • Changes in arterial stiffness (pulse-wave velocity) [ Time Frame: During and for the 1 hour after the exposure ] [ Designated as safety issue: No ]

Enrollment: 15
Study Start Date: March 2008
Study Completion Date: May 2008
Primary Completion Date: May 2008 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: 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)
Drug: Endothelin-1
Intra-arterial infusion of Endothelin-1 at 5pmol/min for 1 hour during venous occlusion plethysmography
Other Names:
  • ET-1
  • American Peptides - 88-1-10 (ET-1)
Experimental: 2
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
Drug: BQ-123 and BQ-788
1 hour intra-arterial infusion of BQ-123 at 10nmol/min followed by co-infusion of BQ-788 at 1nmol/min for a further hour during forearm venous occlusion plethysmography
Other Names:
  • American Peptides - 88-2-10 (BQ-123)
  • American Peptides - 88-2-55 (BQ-788)
Experimental: 3
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)
Drug: Endothelin-1
Intra-arterial infusion of Endothelin-1 at 5pmol/min for 1 hour during venous occlusion plethysmography
Other Names:
  • ET-1
  • American Peptides - 88-1-10 (ET-1)
Experimental: 4
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
Drug: BQ-123 and BQ-788
1 hour intra-arterial infusion of BQ-123 at 10nmol/min followed by co-infusion of BQ-788 at 1nmol/min for a further hour during forearm venous occlusion plethysmography
Other Names:
  • American Peptides - 88-2-10 (BQ-123)
  • American Peptides - 88-2-55 (BQ-788)

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

Ages Eligible for Study:   18 Years to 35 Years
Genders Eligible for Study:   Male
Accepts Healthy Volunteers:   Yes
Criteria

Inclusion Criteria:

  • Healthy male volunteers

Exclusion Criteria:

  • Use of regular medication
  • Cigarette smoking
  • Significant occupational exposure to air pollution
  • Intercurrent illness
  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: NCT00745693

Locations
Sweden
Umeå University
Umeå, Västerbottens, Sweden, SE-901 87
Sponsors and Collaborators
University of Edinburgh
Umeå University
Investigators
Principal Investigator: Jeremy P Langrish, MB BCh MRCP University of Edinburgh
Study Director: Anders Blomberg, MD Umeå University
Study Director: Thomas Sandström, MD Umeå University
Study Director: David E Newby, MD FRCP University of Edinburgh
  More Information

Publications:
Additional publications automatically indexed to this study by ClinicalTrials.gov Identifier (NCT Number):
Responsible Party: Dr Jeremy Langrish, University of Edinburgh
ClinicalTrials.gov Identifier: NCT00745693     History of Changes
Other Study ID Numbers: Res08/A116
Study First Received: September 2, 2008
Last Updated: September 4, 2008
Health Authority: Sweden: Regional Ethical Review Board

Keywords provided by University of Edinburgh:
Endothelin
Air pollution
Diesel exhaust
Vascular function
exposure

Additional relevant MeSH terms:
Coronary Disease
Coronary Artery Disease
Myocardial Ischemia
Heart Diseases
Cardiovascular Diseases
Vascular Diseases
Arteriosclerosis
Arterial Occlusive Diseases
Cyclo(Trp-Asp-Pro-Val-Leu)
BQ 788
Antihypertensive Agents
Cardiovascular Agents
Therapeutic Uses
Pharmacologic Actions

ClinicalTrials.gov processed this record on September 16, 2014