Diesel Exhaust and Vascular Function (CVDTRAP4)

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

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.

Study Overview

• Status: Unknown
• Conditions: Cardiovascular Effects
• Intervention / Treatment: Other: Diesel Exhaust; Drug: Terazosin; Drug: placebo; Other: Filtered Air

• Study Type: Interventional
• Enrollment (Anticipated): 24
• Phase: Not Applicable

Contacts and Locations

Study Locations

• United States
  • Washington
    • Seattle, Washington, United States, 98195
      • Recruiting
      • University of Washington Medical Center

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 49 years (Adult)
• Accepts Healthy Volunteers: Yes
• Genders Eligible for Study: All

Description

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

Study Plan

How is the study designed?

Design Details

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

Number of Arms

4

Arms and Interventions

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

What is the study measuring?

Primary Outcome Measures

Outcome Measure	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

Collaborators and Investigators

• Sponsor: University of Washington
• Collaborators: National Institute of Environmental Health Sciences (NIEHS); Environmental Protection Agency (EPA)
• Investigators: Principal Investigator: Joel D Kaufman, MD, MPH, University of Washington

Study record dates

Study Major Dates

• Study Start: January 1, 2012
• Primary Completion (Anticipated): December 1, 2015
• Study Completion (Anticipated): December 1, 2015

Study Registration Dates

• First Submitted: January 5, 2012
• First Submitted That Met QC Criteria: January 11, 2012
• First Posted (Estimate): January 12, 2012

Study Record Updates

• Last Update Posted (Estimate): August 3, 2015
• Last Update Submitted That Met QC Criteria: July 30, 2015
• Last Verified: July 1, 2015

More Information

Terms related to this study

• Keywords: blood pressure; air pollution; vasoconstriction; diesel exhaust
• Additional Relevant MeSH Terms: Physiological Effects of Drugs; Adrenergic Antagonists; Adrenergic Agents; Neurotransmitter Agents; Molecular Mechanisms of Pharmacological Action; Urological Agents; Adrenergic alpha-1 Receptor Antagonists; Adrenergic alpha-Antagonists; Terazosin
• Other Study ID Numbers: 39833-D; P50ES015915 (U.S. NIH Grant/Contract)