Effects of Sequential Exposure to Nitrogen Dioxide and Ozone in Healthy Adult Human Volunteers.

NCT02133586 | Completed

• 1 other identifier: ENDZONE
• Study Type: interventional
• Target: 54
• Locations: 1 country
• Sites: 1

Brief Summary

The U.S. Environmental Protection Agency has traditionally examined the effects of single pollutant exposure on human health outcomes; however, to provide a better assessment of pollutant exposure-associated effect on human health the Agency is moving toward a multi-pollutant approach. Ozone (O3) and nitrogen dioxide (NO2) are national ambient air quality standards (NAAQS) criteria pollutants that are major constituents of ambient air pollution. This study will address the Agency's goals by investigating the cardiopulmonary health effects of sequential exposure to O3 and NO2 in healthy adult human volunteers. The findings of this study will provide data that will inform risk assessment models for O3 and NO2 exposures. Additionally, the findings will provide insight into how the human health effects of multi-pollutant exposures differ from those of single pollutant exposures.

Conditions

Respiratory Depression

Keywords

Air pollution; Ozone; Nitrogen dioxide; Lung function; Cytokines

Outcome Measures

Primary Outcomes (1)

• Pulmonary Function

  Measurements are taken pre-exposure ("baseline" measurement), immediately post-exposure, and 24 hours post-exposure. Changes in forced vital capacity (FVC) and forced expiratory volume in one second (FEV1) will be assessed as indicators of change in pulmonary function.

  Pre-exposure ("baseline"), immediately post-exposure, and 24 hours post-exposure

Secondary Outcomes (1)

• Heart Rate Variability

  Pre-exposure ("baseline"), immediately post-exposure, and 24 hours post-exposure

Other Outcomes (1)

• Plasma cytokine levels

  Pre-exposure ("baseline"), immediately post-exposure, and 24 hours post-exposure

Study Arms (4)

Clean Air - O3

PLACEBO COMPARATOR

Day #1: Two-hour exposure to clean, filtered air with intermittent exercise. Day #2: Two-hour exposure to 300ppb ozone (beginning approximately 22 hours after completion of the Day #1 exposure) with intermittent exercise. Day #3: Follow-up (no exposure)

Other: Ozone

NO2-O3

EXPERIMENTAL

Day #1: Two-hour exposure to 500ppb nitrogen dioxide with intermittent exercise. Day #2: Two-hour exposure to 300ppb ozone (beginning approximately 22 hours after completion of the Day #1 exposure) with intermittent exercise. Day #3: Follow-up (no exposure)

Other: Ozone; Other: Nitrogen dioxide

Clean Air - NO2

PLACEBO COMPARATOR

Day #1: Two-hour exposure to clean, filtered air with intermittent exercise. Day #2: Two-hour exposure to 500ppb nitrogen dioxide (beginning approximately 22 hours after completion of the Day #1 exposure) with intermittent exercise. Day #3: Follow-up (no exposure)

Other: Nitrogen dioxide

O3 - NO2

EXPERIMENTAL

Day #1: Two-hour exposure to 300ppb ozone with intermittent exercise. Day #2: Two-hour exposure to 500ppb nitrogen dioxide (beginning approximately 22 hours after completion of the Day #1 exposure) with intermittent exercise. Day #3: Follow-up (no exposure)

Other: Ozone; Other: Nitrogen dioxide

Interventions

Ozone OTHER

Exposure to 300ppb ozone with intermittent exercise as either the first exposure in a two-exposure series or as the second exposure approximately 22 hours after the first exposure (either clean air or nitrogen dioxide) in a two-exposure series.

Also known as: Trioxygen, CAS #10028-15-6

Clean Air - O3; NO2-O3; O3 - NO2

Nitrogen dioxide OTHER

Exposure to 500ppb nitrogen dioxide with intermittent exercise as either the first exposure in a two-exposure series or as the second exposure approximately 22 hours after the first exposure (either clean air or ozone) in a two-exposure series.

Also known as: Nitrogen peroxide, CAS 310102-44-0

Clean Air - NO2; NO2-O3; O3 - NO2

Eligibility Criteria

• Age: 18 Years - 40 Years
• Sex: all
• Healthy Volunteers: Yes
• Age Groups: Adult (18-64)

You may qualify if:

• Healthy men and women between 18 and 40 years of age.
• Physical conditioning allowing intermittent, moderate exercise for two hours.
• Ability to complete the exposure exercise regimen without reaching 80% of predicted maximal heart rate.
• Normal baseline 12-lead baseline EKG or if not normal the EKG must be approved by a study cardiologist.
• Normal lung function
• Forced vital capacity (FVC) \>75% of that predicted for gender, ethnicity, age, and height (according to National Health and Nutrition Examination Survey \[NHANESIII\] guidelines).
• Forced expiratory volume in one second (FEV1) \> 75% of that predicted for gender, ethnicity, age, and height (according to NHANESIII guidelines).
• FEV1/FVC ration \>75% of predicted values (according to NHANESIII guidelines).
• Oxygen saturation \>96% on room air.

You may not qualify if:

• Individuals with a history of acute or chronic cardiovascular disease, chronic respiratory disease, diabetes, rheumatologic disease, or immunodeficiency state.
• Individuals with a Framingham risk score (Hard Coronary Heard Disease \[HCHD\] 10-year risk) ≥10.
• Individuals with asthma or a history of asthma.
• Individuals who are allergic to chemical vapors or gases.
• Females who are pregnant, attempting to become pregnant, or breastfeeding.
• Individuals who have smoked tobacco during the last five years or those with a history of \>5 pack years.
• Individuals living with a smoker who smokes inside the house.
• Individuals with a body mass index (BMI) \>30 or \<18. Body mass index is calculated by dividing the weight in kilograms by the square of the height in meters.
• Individuals with occupational exposures to high levels of vapors, dust, gases, or fumes on an on-going basis.
• Individuals with uncontrolled hypertension (≥150 systolic or ≥90 diastolic).
• Individuals that do not understand or speak English.
• Individuals that are unable to perform the exercise required for the study.
• Individuals that are taking beta blocker medications.
• Individuals with a history of skin allergies to adhesives used in securing EKG electrodes.
• Individuals with unspecified diseases, conditions, or medications that might influence the responses to the exposures, as judged by the medical staff.

Sponsors & Collaborators

• Environmental Protection Agency (EPA): lead

Study Sites (1)

E.P.A. Human Studies Facility

Chapel Hill, North Carolina, 27514, United States

Location

MeSH Terms

Conditions

Respiratory Insufficiency

Interventions

Ozone; Nitrogen Dioxide

Condition Hierarchy (Ancestors)

Respiration Disorders; Respiratory Tract Diseases

Intervention Hierarchy (Ancestors)

Oxygen; Gases; Inorganic Chemicals; Nitrogen Oxides; Nitrogen Compounds; Oxides; Oxygen Compounds

Study Officials

• Shaun McCullough, M.S., Ph.D.

  U.S. Environmental Protection Agency

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: not applicable
• Allocation: RANDOMIZED
• Masking: SINGLE
• Who Masked: PARTICIPANT
• Purpose: BASIC SCIENCE
• Intervention Model: CROSSOVER
• Sponsor Type: FED
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Research Biologist

Study Record Dates

• First Submitted: May 6, 2014
• First Posted: May 8, 2014
• Study Start: January 1, 2014
• Primary Completion: January 1, 2016
• Study Completion: January 1, 2016
• Last Updated: August 17, 2020

Record last verified: 2020-08

Locations

US (1)