Diesel Exhaust and Vascular Function

Study Overview
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Brief Summary
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Double-blind, sham- and placebo-controlled randomized study of effects of freshly-generated diluted diesel exhaust inhalation on vascular function. To examine role of adrenergic system a trial of alpha-blocker terazosin is also used. Each participant completes four study sessions, separated by at least three weeks: 1) Diesel exhaust inhalation (DE, controlled at 300 micrograms/cubic meter for two hours) and terazosin (2 mg prior to inhalation exposure); 2) DE plus placebo (matched for terazosin); 3) filtered air plus terazosin; and 4) filter air plus placebo. The investigators assess outcomes of blood pressure, forearm brachial artery ultrasound, and plasma measures of endothelial activation. The investigators hypothesize that DE exposure will be associated with increased blood pressure, decreased brachial artery diameter, and increased circulating endothelins, and that these effects will be attenuated by terazosin administration.

Official Title
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Effect of Diesel Exhaust Exposures on Vascular Function in Humans: The Role of Sympathetic Activation

Conditions
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Cardiovascular Effects

Intervention / Treatment
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* Other: Diesel Exhaust
* Other: Filtered Air
* Drug: Terazosin
* Drug: placebo


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: healthy without chronic illness Body Mass Index 18.5 - 26.0 tolerates 2 mg terazosin dose without unacceptable symptoms able to return for four exposure sessions Exclusion Criteria: any chronic disease tobacco user asthma elevated cholesterol obesity hypertension diabetes any chronic cardiovascular or pulmonary disease pregnancy or unwillingness to use effective contraception, if female

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 49 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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Accepts Healthy Volunteers

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Prevention
Allocation: Randomized
Intervention Model: Crossover Assignment
Masking: Triple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Diesel Exhaust + Terazosin<br> | Other: Diesel Exhaust<br>* Freshly generated diesel exhaust, diluted to 300 micrograms/cubic meter. Exposures are two hours in duration.<br>Drug: Terazosin<br>* 2 mg by mouth, 90 minutes prior to exposure initiation<br>|
| Experimental: Diesel Exhaust + placebo<br> | Other: Diesel Exhaust<br>* Freshly generated diesel exhaust, diluted to 300 micrograms/cubic meter. Exposures are two hours in duration.<br>Drug: placebo<br>* capsule, identical in appearance to terazosin capsule, by mouth, 30 minutes prior to exposure initiation<br>|
| Sham Comparator: Filtered Air + terazosin<br> | Other: Filtered Air<br>* Sham exposure, identical to conditions of diesel exhaust exposure, but with only air filtered of particles and volatile organic compound gases<br>Drug: Terazosin<br>* 2 mg by mouth, 90 minutes prior to exposure initiation<br>|
| Sham Comparator: Filtered air + placebo<br> | Other: Filtered Air<br>* Sham exposure, identical to conditions of diesel exhaust exposure, but with only air filtered of particles and volatile organic compound gases<br>Drug: placebo<br>* capsule, identical in appearance to terazosin capsule, by mouth, 30 minutes prior to exposure initiation<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Systolic Blood Pressure |  | 30-90 minutes after exposure initiation | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Brachial artery diameter | The investigators anticipate vasoconstriction (post-exposure vs. pre-exposure) as observed in this conduit artery in response to exposure to Diesel Exhaust, compared to Filtered Air sham exposure. | Assessed 30 minutes prior to exposure and 30 minutes post-exposure | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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diesel exhaust, air pollution, vasoconstriction, blood pressure