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

May 15, 2024 updated by: University of Edinburgh
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

Study Overview

Status

Completed

Conditions

Intervention / Treatment

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 Type

Interventional

Enrollment (Actual)

15

Phase

  • Not Applicable

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Locations

  • Sweden
    • Västerbottens
      • Umeå, Västerbottens, Sweden, SE-901 87
        • Umeå University

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

18 years to 35 years (Adult)

Accepts Healthy Volunteers

Yes

Description

Inclusion Criteria:

  • Healthy male volunteers

Exclusion Criteria:

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

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: Basic Science
  • Allocation: Randomized
  • Interventional Model: Crossover Assignment
  • Masking: Triple

Arms and Interventions

Participant Group / Arm
Intervention / Treatment
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)

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Time Frame
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
2 hours after exposure

Secondary Outcome Measures

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

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

University of Edinburgh

Collaborators

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

Publications and helpful links

The person responsible for entering information about the study voluntarily provides these publications. These may be about anything related to the study.

General Publications

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start

March 1, 2008

Primary Completion (Actual)

May 1, 2008

Study Completion (Actual)

May 1, 2008

Study Registration Dates

First Submitted

September 2, 2008

First Submitted That Met QC Criteria

September 2, 2008

First Posted (Estimated)

September 3, 2008

Study Record Updates

Last Update Posted (Actual)

May 17, 2024

Last Update Submitted That Met QC Criteria

May 15, 2024

Last Verified

September 1, 2008

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

  • Res08/A116

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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