Mental Stress & Diesel Exhaust on Cardiovascular Health

Study Overview
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Brief Summary
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This study uses an experimental design to conduct a double-blind, randomized, crossover study where participants receive both diesel exhaust and a mental stress test in a controlled setting. My hypothesis is that the synergistic effect of stress and air pollution will result in higher levels of stress and inflammation (measured via biological markers) as well as poorer cardiovascular disease related outcomes compared to the independent effect of each exposure separately.

Official Title
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Effects of Mental Stress and Diesel Exhaust on Cardiovascular Health

Conditions
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Blood Pressure, Inflammation, Catecholamines

Intervention / Treatment
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* Behavioral: Trier social stress test
* Other: Diesel exhaust


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Non-smokers without history of high blood pressure, asthma, diabetes, high cholesterol, post-traumatic stress disorder (PTSD) or any other chronic condition that requires ongoing care. Exclusion Criteria: Smoking: We rule out active smoking by checking urine cotinine during our study. History of high blood pressure: We objectively measure BP during in-person screening and exclude those with blood pressure (>130/85 mmHg). Asthmatic: Spirometry is done at screening to rule out asthma. Diabetic: We obtain fasting blood sugar to rule out diabetes at screening (>125 mg/dL) Cholesterol: We obtain fasting blood lipid levels to rule out hypercholesterolemia at screening (>200 mg/dL). History of PTSD: Subjects will be asked about prior PTSD diagnosis during the phone and in person screen. Any other chronic condition requiring ongoing care based on medication use. A body mass index (weight in kilograms divided by height in meters squared) greater than 26 and less than 18.5 A female of childbearing age with a positive pregnancy test A female of childbearing age who is unwilling to use effective contraception during the study

Ages Eligible for Study
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Minimum Age: 22 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: Other
Allocation: Randomized
Intervention Model: Crossover Assignment
Masking: Triple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| No Intervention: Filtered Air<br>Subjects sit in a room for two hours breathing in filtered air which resembles levels of air pollution found in the ambient environment | |
| Active Comparator: Diesel Exhaust<br>Subjects sit in a room for two hours breathing in diesel exhaust at 200 micrograms of meter cubed. | Other: Diesel exhaust<br>* Diesel exhaust is an air pollutant found in the environment and produced by cars, trucks and other transportation modes (e.g. trains, planes).<br>|
| Active Comparator: TSST/Stress only<br>Subjects undergo a mental stress test, known as the Trier Social Stress Test (TSST), which involves a public speaking and math task. | Behavioral: Trier social stress test<br>* Subjects are asked to give a 5 minute speech on a topic selected by the investigator. Then they are asked to subtract 7 from 758.<br>* Other names: TSST;|
| Active Comparator: Diesel Exhaust and stress<br>Subjects sit in a room for two hours breathing in diesel exhaust at 200 micrograms of meter cubed and are subject to a mental stress test (TSST) which involves a public speaking and math task. | Behavioral: Trier social stress test<br>* Subjects are asked to give a 5 minute speech on a topic selected by the investigator. Then they are asked to subtract 7 from 758.<br>* Other names: TSST;Other: Diesel exhaust<br>* Diesel exhaust is an air pollutant found in the environment and produced by cars, trucks and other transportation modes (e.g. trains, planes).<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Change in norepinephrine | Urinary norepinephrine in ng/mg | Change in norepinephrine from baseline (pre-exposure) to immediately after exposure | 
| Change in epinephrine | Urinary epinephrine in ng/mg | Change in epinephrine from baseline (pre-exposure) to immediately after exposure | 
| Change in dopamine | Urinary dopamine in ng/mg | Change in dopamine from baseline (pre-exposure) to immediately after exposure | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Change in d-dimer | plasma d-dimer (ug/ml) is a measure of coagulation | change in d-dimer from baseline (pre-exposure) to six hours post exposure | 
| Change in fibrinogen | plasma fibrinogen (mg/dl) is a measure of coagulation | change in fibrinogen from baseline (pre-exposure) to six hours post exposure | 
| Change in interleukin-6 (IL-6) | plasma IL-6, measured in pg/ml, is a marker of inflammation | change in IL-6 from baseline (pre-exposure) to immediately after exposure | 
| Change in tumor necrosis factor alpha (TNF-a) | plasma TNF-a, measured in pg/ml, is a marker of inflammation | change in TNF-a from baseline (pre-exposure) to immediately after exposure | 
| Change in interleukin-1b (IL-1b) | plasma IL-1b, measured in pg/ml, is a marker of inflammation | change in IL-1b from baseline (pre-exposure) to immediately after exposure |