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Sponsors and Collaborators: |
University of Washington National Institutes of Health (NIH) |
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Information provided by: | University of Washington |
ClinicalTrials.gov Identifier: | NCT00434005 |
Objectives: This proposal addresses the overall hypothesis that ambient fine particulate matter exerts cardiovascular health effects via alteration of endothelial homeostasis, through a mechanism mediated by oxidative stress. This project will use a controlled human inhalation exposure to diesel exhaust particulate (DEP) as a model to address the following objectives: 1) Determine whether exposure to inhaled DEP is associated with endothelial dysfunction in a concentration-related manner; 2) Determine whether exposure to inhaled DEP is associated with evidence of systemic oxidative stress; and 3) Determine whether antioxidant supplementation blunts the DEP effect on endothelial function.
Condition | Intervention |
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Healthy |
Drug: N-acetylcysteine, ascorbate Drug: Placebo |
Study Type: | Interventional |
Study Design: | Prevention, Randomized, Double Blind (Subject, Caregiver, Investigator, Outcomes Assessor), Placebo Control, Crossover Assignment, Safety/Efficacy Study |
Official Title: | Effect of Diesel Exhaust Particulate Exposures on Endothelial Function in Humans - the Role of Oxidative Stress |
Estimated Enrollment: | 24 |
Study Start Date: | July 2008 |
Estimated Study Completion Date: | June 2013 |
Estimated Primary Completion Date: | June 2013 (Final data collection date for primary outcome measure) |
Arms | Assigned Interventions |
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Diesel Exhaust: Experimental |
Drug: N-acetylcysteine, ascorbate
NAC: 600mg twice daily for the day prior to exposure and 1x pre-exposure Ascorbate: 500mg twice daily for 7 days prior to exposure
Drug: Placebo
matched appearance to acetylcysteine and ascorbate intervention
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Filtered Air: Sham Comparator |
Drug: N-acetylcysteine, ascorbate
NAC: 600mg twice daily for the day prior to exposure and 1x pre-exposure Ascorbate: 500mg twice daily for 7 days prior to exposure
Drug: Placebo
matched appearance to acetylcysteine and ascorbate intervention
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OBJECTIVES Evidence of the cardiovascular health effects of both acute and chronic exposure to ambient fine particulate matter (PM) has continued to accumulate in epidemiologic and experimental studies, without a demonstrated coherent pathophysiologic explanation. At the same time, the role of endothelial homeostasis in the development and triggering of cardiovascular disease has become more clear and compelling. Importantly, oxidative stress has emerged as a potential link between these two developments: Oxidative stress is known to play a role in endothelial dysfunction and is exerted by components of PM, especially of PM from combustion products. Based on this we propose an overall hypothesis: Inhalation of combustion-derived particles impact cardiovascular health by impairing endothelial function, through mechanisms mediated by increased oxidative stress.
Diesel exhaust particulate (DEP), an important contributor to ambient fine PM, has been demonstrated to exert oxidative stress in experimental systems.
We propose a series of experiments to explore whether human exposure to DEP results in alteration of endothelial homeostasis and evidence of oxidative stress, and whether an antioxidant regimen can blunt the effects on endothelial function.
The objectives of this proposed research are to address the following specific hypotheses:
Ages Eligible for Study: | 18 Years to 49 Years |
Genders Eligible for Study: | Both |
Accepts Healthy Volunteers: | Yes |
Inclusion Criteria:
Exclusion Criteria:
Contact: Mary R Aulet, MEd | 206-616-6525 | mraulet@u.washington.edu |
Contact: Jason Allen, N.D., MPH | 206-616-6525 | drjnd@u.washington.edu |
United States, Washington | |
Northlake Laboratory | Recruiting |
Seattle, Washington, United States, 98105 | |
Contact: Mary Aulet, MEd mraulet@u.washington.edu | |
Contact: Jason Allen, ND, MPH drjnd@u.washington.edu | |
Principal Investigator: Joel D Kaufman, MD, MPH |
Principal Investigator: | Joel D Kaufman, M.D., MPH | University of Washington |
Responsible Party: | University of Washington ( Joel Kaufman, MD, MPH ) |
Study ID Numbers: | 1369, R830954, R827355, MO1RR-00037, ES015915, ES013195 |
Study First Received: | August 25, 2006 |
Last Updated: | January 22, 2009 |
ClinicalTrials.gov Identifier: | NCT00434005 History of Changes |
Health Authority: | United States: Institutional Review Board |
Air pollution diesel antioxidant oxidative stress |
endothelial HRV BAR |
Antioxidants Expectorants Acetylcysteine Stress |
Healthy Antiviral Agents N-monoacetylcystine |
Respiratory System Agents Anti-Infective Agents Antioxidants Molecular Mechanisms of Pharmacological Action Physiological Effects of Drugs Antiviral Agents Protective Agents |
Pharmacologic Actions Expectorants Therapeutic Uses Free Radical Scavengers Acetylcysteine N-monoacetylcystine Antidotes |