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

This study is currently recruiting participants. (see Contacts and Locations)
Verified May 2014 by Environmental Protection Agency (EPA)
Sponsor:
Information provided by (Responsible Party):
Shaun D. McCullough, Environmental Protection Agency (EPA)
ClinicalTrials.gov Identifier:
NCT02133586
First received: May 6, 2014
Last updated: NA
Last verified: May 2014
History: No changes posted
  Purpose

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.


Condition Intervention
Respiratory Depression
Other: Ozone
Other: Nitrogen dioxide

Study Type: Interventional
Study Design: Allocation: Randomized
Intervention Model: Crossover Assignment
Masking: Single Blind (Subject)
Primary Purpose: Basic Science
Official Title: Effects of Sequential Exposure to Nitrogen Dioxide and Ozone in Healthy Adult Human Volunteers.

Resource links provided by NLM:


Further study details as provided by Environmental Protection Agency (EPA):

Primary Outcome Measures:
  • Pulmonary Function [ Time Frame: Pre-exposure ("baseline"), immediately post-exposure, and 24 hours post-exposure ] [ Designated as safety issue: No ]
    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.


Secondary Outcome Measures:
  • Heart Rate Variability [ Time Frame: Pre-exposure ("baseline"), immediately post-exposure, and 24 hours post-exposure ] [ Designated as safety issue: No ]

Other Outcome Measures:
  • Plasma cytokine levels [ Time Frame: Pre-exposure ("baseline"), immediately post-exposure, and 24 hours post-exposure ] [ Designated as safety issue: No ]

Estimated Enrollment: 40
Study Start Date: January 2014
Estimated Primary Completion Date: January 2016 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Placebo Comparator: Clean Air - O3

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
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.
Other Names:
  • Trioxygen
  • CAS #10028-15-6
Experimental: NO2-O3

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
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.
Other Names:
  • Trioxygen
  • CAS #10028-15-6
Other: Nitrogen dioxide
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.
Other Names:
  • Nitrogen peroxide
  • CAS 310102-44-0
Placebo Comparator: Clean Air - NO2

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
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.
Other Names:
  • Nitrogen peroxide
  • CAS 310102-44-0
Experimental: O3 - NO2

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
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.
Other Names:
  • Trioxygen
  • CAS #10028-15-6
Other: Nitrogen dioxide
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.
Other Names:
  • Nitrogen peroxide
  • CAS 310102-44-0

  Show Detailed Description

  Eligibility

Ages Eligible for Study:   18 Years to 45 Years
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   Yes
Criteria

Inclusion Criteria:

  1. Healthy men and women between 18 and 45 years of age.
  2. Physical conditioning allowing intermittent, moderate exercise for two hours.
  3. Ability to complete the exposure exercise regimen without reaching 80% of predicted maximal heart rate.
  4. Normal baseline 12-lead baseline EKG or if not normal the EKG must be approved by a study cardiologist.
  5. Normal lung function

    1. Forced vital capacity (FVC) >75% of that predicted for gender, ethnicity, age, and height (according to National Health and Nutrition Examination Survey [NHANESIII] guidelines).
    2. Forced expiratory volume in one second (FEV1) > 75% of that predicted for gender, ethnicity, age, and height (according to NHANESIII guidelines).
    3. FEV1/FVC ration >75% of predicted values (according to NHANESIII guidelines).
  6. Oxygen saturation >96% on room air.

Exclusion Criteria:

  1. Individuals with a history of acute or chronic cardiovascular disease, chronic respiratory disease, diabetes, rheumatologic disease, or immunodeficiency state.
  2. Individuals with a Framingham risk score (Hard Coronary Heard Disease [HCHD] 10-year risk) ≥10.
  3. Individuals with asthma or a history of asthma.
  4. Individuals who are allergic to chemical vapors or gases.
  5. Females who are pregnant, attempting to become pregnant, or breastfeeding.
  6. Individuals that are unwilling or unable to stop taking vitamin C or E, or medications that may impact the results of ozone challenge such at least two weeks prior to the study and for the duration of the study. Medications not specifically mentioned here may be reviewed by the investigators prior to an individual's inclusion in the study.
  7. Individuals who have smoked tobacco during the last five years or those with a history of >5 pack years.
  8. Individuals living with a smoker who smokes inside the house.
  9. Individuals with a body mass index (BMI) >35 or <18. Body mass index is calculated by dividing the weight in kilograms by the square of the height in meters.
  10. Individuals with occupational exposures to high levels of vapors, dust, gases, or fumes on an on-going basis.
  11. Individuals with uncontrolled hypertension (≥150 systolic or ≥90 diastolic).
  12. Individuals that do not understand or speak English.
  13. Individuals that are unable to perform the exercise required for the study.
  14. Individuals that are taking beta blocker medications.
  15. Individuals with a history of skin allergies to adhesives used in securing EKG electrodes.
  16. Individuals with unspecified diseases, conditions, or medications that might influence the responses to the exposures, as judged by the medical staff.
  17. Individuals that are unwilling or unable to stop taking over-the-counter pain medications such as aspirin, ibuprofen (Advil, Motrin), naproxen (Aleve), or other non-steroidal anti-inflammatory ("NSAID") medications for 48 hours prior to the exposures and post-exposure visits.
  18. Individuals that are taking systemic steroids or beta-blocker medications.
  19. Individuals with a hemoglobin A1c (HbA1c) level > 6.4%.

Temporary Exclusion Criteria

  1. Individuals with active seasonal allergies during the time of participation in the study.
  2. Individuals suffering from acute respiratory illness within four weeks prior to any of the study exposure series.
  3. Individuals that have been exposed to smoke and fumes within 24 hours of any study visit.
  4. Individuals that have consumed alcohol within 24 hours of any study visit.
  5. Individuals that have engaged in strenuous exercise within 24 hours of any study visit.
  6. Individuals that have been exposed to ozone-based home air purifiers within 24 hours of any study visit.
  7. Individuals that have been exposed to unvented household combustion sources (gas stoves, lit fireplaces, oil/kerosene heaters) within 48 hours of any study visit.
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT02133586

Contacts
Contact: Bridget Smallwood-Hurdle, MSPH 919-966-0610 smallwood-hurdle.bridget@epa.gov
Contact: Patrice Ratliffe 919-966-0607 ratliffe.patrice@epa.gov

Locations
United States, North Carolina
E.P.A. Human Studies Facility Recruiting
Chapel Hill, North Carolina, United States, 27514
Contact: Shaun McCullough, M.S., Ph.D.    919-843-8031    mccullough.shaun@epa.gov   
Principal Investigator: Shaun McCullough, M.S., Ph.D.         
Sponsors and Collaborators
Investigators
Principal Investigator: Shaun McCullough, M.S., Ph.D. U.S. Environmental Protection Agency
  More Information

Additional Information:
No publications provided

Responsible Party: Shaun D. McCullough, Research Biologist, Environmental Protection Agency (EPA)
ClinicalTrials.gov Identifier: NCT02133586     History of Changes
Other Study ID Numbers: ENDZONE
Study First Received: May 6, 2014
Last Updated: May 6, 2014
Health Authority: United States: Federal Government

Keywords provided by Environmental Protection Agency (EPA):
Air pollution
Ozone
Nitrogen dioxide
Lung function
Cytokines

Additional relevant MeSH terms:
Depression
Respiratory Insufficiency
Behavioral Symptoms
Respiration Disorders
Respiratory Tract Diseases

ClinicalTrials.gov processed this record on September 18, 2014