Effect of Diesel Exhaust Particulate Exposures on Endothelial Function in Humans

Study Results

Results pending

The study team has not published outcome measurements, participant flow, or safety data for this trial yet. Check back later for updates.

Basic Information

Get a concise snapshot of the trial, including recruitment status, study phase, enrollment targets, and key timeline milestones.

Recruitment Status

COMPLETED

Clinical Phase

NA

Total Enrollment

24 participants

Study Classification

INTERVENTIONAL

Study Start Date

2008-07-31

Study Completion Date

2010-08-31

Brief Summary

Review the sponsor-provided synopsis that highlights what the study is about and why it is being conducted.

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.

Related Clinical Trials

Explore similar clinical trials based on study characteristics and research focus.

Diesel Exhaust and Vascular Function

NCT01508637

Cardiovascular Effects

UNKNOWN NA

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

NCT00745693

Coronary Disease

COMPLETED NA

Acute Exposure to Diesel: Prolong Effects on Inflammation and Vasculature

NCT04098536

Atherosclerosis

RECRUITING NA

Diesel Exhaust and Mechanism of Asthma

NCT01699204

Asthma

COMPLETED NA

Diesel Exhaust Inhalation, Systemic Nitric Oxide Inhibition and Cardiac Output

NCT01060930

Vascular Function in Healthy Volunteers

COMPLETED NA

Detailed Description

Dive into the extended narrative that explains the scientific background, objectives, and procedures in greater depth.

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:

1. Human exposure to inhaled DEP (at concentrations approximating 0, 100, 200 μg PM2.5/m3 \[PM less than 2.5 microns in aerodynamic diameter\]) results in concentration-related alteration of endothelial homeostasis, as reflected in ultrasonographic measurement of the brachial artery, plasma markers of endothelial homeostasis (endothelin-1, ICAM-1 \[intercellular adhesion molecule-1\], e-selectin, nitric oxide metabolites nitrate \[NO3-\] and nitrite \[NO2-\], IL-6, and TNF-α), and markers of thrombosis associated with endothelial activation or injury (plasminogen activator inhibitor-1 \[PAI-1\], Von Willebrand's factor \[VWF\], and D-dimer).
2. Human exposure to inhaled DEP at 200 µg PM2.5/m3 results in evidence of systemic oxidative stress as assessed by markers in plasma and urine (isoprostane F-2α).
3. Reduction in oxidant stress by ascorbate and N-acetylcysteine supplementation blunts the effect of inhaled DEP on endothelial function, as determined by ultrasonographic assessment of the brachial artery, plasma markers of endothelial homeostasis, or markers of thrombosis associated with endothelial activation.

Conditions

See the medical conditions and disease areas that this research is targeting or investigating.

Healthy

Study Design

Understand how the trial is structured, including allocation methods, masking strategies, primary purpose, and other design elements.

Allocation Method

RANDOMIZED

Intervention Model

CROSSOVER

Primary Study Purpose

PREVENTION

Blinding Strategy

QUADRUPLE

Participants Caregivers Investigators Outcome Assessors

Study Groups

Review each arm or cohort in the study, along with the interventions and objectives associated with them.

Diesel Exhaust

Group Type EXPERIMENTAL

N-acetylcysteine, ascorbate

Intervention Type DRUG

NAC: 600mg twice daily for the day prior to exposure and 1x pre-exposure Ascorbate: 500mg twice daily for 7 days prior to exposure

Placebo

Intervention Type DRUG

matched appearance to acetylcysteine and ascorbate intervention

Filtered Air

Group Type SHAM_COMPARATOR

N-acetylcysteine, ascorbate

Intervention Type DRUG

NAC: 600mg twice daily for the day prior to exposure and 1x pre-exposure Ascorbate: 500mg twice daily for 7 days prior to exposure

Placebo

Intervention Type DRUG

matched appearance to acetylcysteine and ascorbate intervention

Interventions

Learn about the drugs, procedures, or behavioral strategies being tested and how they are applied within this trial.

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

Intervention Type DRUG

Placebo

matched appearance to acetylcysteine and ascorbate intervention

Intervention Type DRUG

Eligibility Criteria

Check the participation requirements, including inclusion and exclusion rules, age limits, and whether healthy volunteers are accepted.

Inclusion Criteria

* Healthy adults aged 18-49.

Exclusion Criteria

* Nonsmokers, no history of hypertension, asthma, diabetes, hypercholesterolemia, or other chronic conditions requiring ongoing medical care. No recent history of antioxidant, vitamin/mineral/botanical, or fatty acid supplementation beyond a daily multi-vitamin.

Minimum Eligible Age

18 Years

Maximum Eligible Age

49 Years

Eligible Sex

ALL

Accepts Healthy Volunteers

Yes