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Cardiopulmonary Responses to Exposure to Ozone and Diesel Exhaust (DEPOZ)

Primary Purpose

Respiratory Depression, Blood Pressure

Status
Completed
Phase
Not Applicable
Locations
United States
Study Type
Interventional
Intervention
ozone
Sponsored by
Environmental Protection Agency (EPA)
About
Eligibility
Locations
Arms
Outcomes
Full info

About this trial

This is an interventional diagnostic trial for Respiratory Depression focused on measuring ozone, diesel, lung function, cardiac electrophysiology, mediators of inflammation and clotting

Eligibility Criteria

18 Years - 55 Years (Adult)All SexesAccepts Healthy Volunteers

Inclusion Criteria:

  • Healthy men and women between 18 and 55 years of age
  • Physical conditioning allowing intermittent, moderate exercise for 2 hours

  • Normal lung function:

    1. FVC > 75 % of that predicted for gender, ethnicity, age and height.
    2. FEV1 > 75 % of that predicted for gender, ethnicity, age and height.
    3. FEV1/FVC ratio > 75 % of predicted values.
  • Oxygen saturation > 96 %.

Exclusion Criteria:

  • A history of acute and chronic cardiovascular disease, chronic respiratory disease, diabetes, rheumatologic diseases, immunodeficiency state, and acute respiratory illness within 4 weeks.
  • Subjects who are asthmatic or have a history of asthma.
  • Allergic to chemical vapors or gases.
  • Any allergic symptoms during the time of participation in the study
  • Female subjects who are currently pregnant, attempting to become pregnant, or breastfeeding
  • Subjects unwilling or unable to stop taking vitamin C or E or medications which may impact the results of the ozone challenge (such as, systemic steroids and beta blockers) at least 2 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 a subject's inclusion in the study.
  • Current and past smokers within 1 year.
  • Uncontrolled hypertension (> 150 systolic, > 90 diastolic).
  • Subjects who do not understand or speak English
  • Subjects unable to perform the moderately active exercise required for the study.
  • Subjects with a history of skin allergies to adhesives used in securing heart rate monitor electrodes.
  • Unspecified diseases or conditions, which in the judgment of the investigator might influence the responses to the exposures, will be a basis for exclusion.
  • Subjects unwilling to stop taking over-the-counter pain medications such as aspirin, Advil, Aleve or other non-steroidal anti-inflammatory medications ("NSAIDS") for 48 hr prior to the exposures and post-exposure visits.
  • Subjects with a marked baseline prolongation of QT/QTc interval (e.g., repeated demonstration of a QTc interval >450 milliseconds (ms))

Sites / Locations

  • US EPA Human Studies Facility

Arms of the Study

Arm 1

Arm 2

Arm 3

Arm 4

Arm Type

Placebo Comparator

Experimental

Experimental

Experimental

Arm Label

Filtered air exposure

Ozone

Diesel Exhaust, No ozone

Ozone + Diesel Exhaust

Arm Description

2 hr exposure to clean, filtered air with intermittent exercise

2 hr exposure to 300 ppb ozone with intermittent exercise

2 hr exposure to whole diesel exhaust (300 ug/m3; gases + particles) with intermittent exercise; no ozone

2 hr exposure to a combination of 300 ppb ozone an 300 ug/m3 whole diesel exhaust with intermittent exercise

Outcomes

Primary Outcome Measures

Lung Function Decrement
Lung function decrements are typically expressed as changes in FEV1 and FVC. Measurements are made pre-exposure (defined as baseline, immediately post exposure, 1-4 hr post exposure, and 24 hr post exposure (follow up).

Secondary Outcome Measures

Heart rate variability

Full Information

First Posted
June 7, 2013
Last Updated
June 10, 2013
Sponsor
Environmental Protection Agency (EPA)
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1. Study Identification

Unique Protocol Identification Number
NCT01874834
Brief Title
Cardiopulmonary Responses to Exposure to Ozone and Diesel Exhaust
Acronym
DEPOZ
Official Title
Cardiopulmonary Responses to Exposure to Ozone and Diesel Exhaust With Moderate Exercise in Healthy Adults
Study Type
Interventional

2. Study Status

Record Verification Date
June 2013
Overall Recruitment Status
Completed
Study Start Date
August 2010 (undefined)
Primary Completion Date
April 2012 (Actual)
Study Completion Date
January 2013 (Actual)

3. Sponsor/Collaborators

Responsible Party, by Official Title
Principal Investigator
Name of the Sponsor
Environmental Protection Agency (EPA)

4. Oversight

Data Monitoring Committee
No

5. Study Description

Brief Summary
The US EPA Clean Air Multiyear research program is moving toward a multi-pollutant approach to the assessment of air pollution in response to recommendations by the NRC 2004 and the BOSC in 2005. Such an approach better reflects the complexity of real-world air pollution problems and parallels evolving scientific and regulatory considerations. Ozone (O3) and diesel exhaust (DE) generally are major and important components of ambient air pollution. This proposed study will address the agency's goals by investigating the cardiopulmonary health effects in healthy human subjects co-exposed to O3 and DE. The findings derived from these exposures will provide NCEA findings for risk assessments of O3 and DE, as well as the Office of Air and Radiation (includes OTAQ and OAQPS) with information relevant to possible modulation of PM-induced health effects and responses by a gaseous co-pollutant for potential standard setting. Additionally the findings will address the fundamental driving principle of the Clean Air Research strategy related to reduction of health due to air pollutant exposures.
Detailed Description
Numerous epidemiological studies have demonstrated an association between acute and chronic exposure to air pollution and various adverse cardiopulmonary effects including mortality, respiratory tract infections, exacerbation of asthma symptoms, chronic bronchitis, ischemic heart disease, and stroke [1] and other health effects. Understanding the components responsible for these effects is difficult because ambient air pollution is a complex mixture of gases and particulate matter (PM). In this complex mixture of ambient air pollution, ozone (O3) and diesel exhaust (DE) are generally major and important components. Controlled exposure of volunteers to either pollutant have resulted in biological effects such as lung physiological changes. However it is not known if co-exposure to both pollutants, similar to polluted ambient air, can induce additive or synergistic effects. Additionally it is also uncertain if exposure to DE, or DE with O3, can alter a subsequent exposure to O3 similar to multiple day exposures that the general population receives. This study proposes to examine whether co-exposures to O3 and DE can induce additive or synergistic effects, and whether a previous DE exposure alters a response upon subsequent exposure to O3. The potential effects of O3 on cardiac electrophysiology are also not clear. Approximately 15 healthy non-smoking volunteers between the ages of 18 and 55 will be exposed in a controlled manner to O3 (approximately mean concentration of 0.3 ppm over the 2 hr exposure period), or diesel exhaust (DE; ~300 µg/m3), or a combined O3 and DE exposure while undergoing moderate intermittent exercise at the EPA Human Studies Facility. A clean air exposure will serve as a control. Primary endpoints for evaluating health effects and surrogate responses are changes in lung function and heart rate variability. In addition, other cardiopulmonary and vascular biological endpoints will be measured, as well as markers of exposure and genetic markers of susceptibility.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Respiratory Depression, Blood Pressure
Keywords
ozone, diesel, lung function, cardiac electrophysiology, mediators of inflammation and clotting

7. Study Design

Primary Purpose
Diagnostic
Study Phase
Not Applicable
Interventional Study Model
Factorial Assignment
Masking
ParticipantInvestigator
Allocation
Randomized
Enrollment
15 (Actual)

8. Arms, Groups, and Interventions

Arm Title
Filtered air exposure
Arm Type
Placebo Comparator
Arm Description
2 hr exposure to clean, filtered air with intermittent exercise
Arm Title
Ozone
Arm Type
Experimental
Arm Description
2 hr exposure to 300 ppb ozone with intermittent exercise
Arm Title
Diesel Exhaust, No ozone
Arm Type
Experimental
Arm Description
2 hr exposure to whole diesel exhaust (300 ug/m3; gases + particles) with intermittent exercise; no ozone
Arm Title
Ozone + Diesel Exhaust
Arm Type
Experimental
Arm Description
2 hr exposure to a combination of 300 ppb ozone an 300 ug/m3 whole diesel exhaust with intermittent exercise
Intervention Type
Other
Intervention Name(s)
ozone
Other Intervention Name(s)
cas # 10028-15-6, trioxygen
Intervention Description
Exposure to 300 ppb ozone with intermittent exercise about 20 hr after exposure to each arm (ie, either air, ozone, diesel exhaust, or ozone combined with diesel exhaust)
Primary Outcome Measure Information:
Title
Lung Function Decrement
Description
Lung function decrements are typically expressed as changes in FEV1 and FVC. Measurements are made pre-exposure (defined as baseline, immediately post exposure, 1-4 hr post exposure, and 24 hr post exposure (follow up).
Time Frame
Immediately post to 24 hr post exposure
Secondary Outcome Measure Information:
Title
Heart rate variability
Time Frame
immediately post to 24 hr post exposure
Other Pre-specified Outcome Measures:
Title
plasma cytokine levels
Description
Inflammation markers such as interleukin 8
Time Frame
immediately post to 24 hr post exposur

10. Eligibility

Sex
All
Minimum Age & Unit of Time
18 Years
Maximum Age & Unit of Time
55 Years
Accepts Healthy Volunteers
Accepts Healthy Volunteers
Eligibility Criteria
Inclusion Criteria: Healthy men and women between 18 and 55 years of age Physical conditioning allowing intermittent, moderate exercise for 2 hours Normal lung function: FVC > 75 % of that predicted for gender, ethnicity, age and height. FEV1 > 75 % of that predicted for gender, ethnicity, age and height. FEV1/FVC ratio > 75 % of predicted values. Oxygen saturation > 96 %. Exclusion Criteria: A history of acute and chronic cardiovascular disease, chronic respiratory disease, diabetes, rheumatologic diseases, immunodeficiency state, and acute respiratory illness within 4 weeks. Subjects who are asthmatic or have a history of asthma. Allergic to chemical vapors or gases. Any allergic symptoms during the time of participation in the study Female subjects who are currently pregnant, attempting to become pregnant, or breastfeeding Subjects unwilling or unable to stop taking vitamin C or E or medications which may impact the results of the ozone challenge (such as, systemic steroids and beta blockers) at least 2 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 a subject's inclusion in the study. Current and past smokers within 1 year. Uncontrolled hypertension (> 150 systolic, > 90 diastolic). Subjects who do not understand or speak English Subjects unable to perform the moderately active exercise required for the study. Subjects with a history of skin allergies to adhesives used in securing heart rate monitor electrodes. Unspecified diseases or conditions, which in the judgment of the investigator might influence the responses to the exposures, will be a basis for exclusion. Subjects unwilling to stop taking over-the-counter pain medications such as aspirin, Advil, Aleve or other non-steroidal anti-inflammatory medications ("NSAIDS") for 48 hr prior to the exposures and post-exposure visits. Subjects with a marked baseline prolongation of QT/QTc interval (e.g., repeated demonstration of a QTc interval >450 milliseconds (ms))
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Michael Madden, PhD
Organizational Affiliation
Environmental Protection Agency (EPA)
Official's Role
Principal Investigator
Facility Information:
Facility Name
US EPA Human Studies Facility
City
Chapel Hill
State/Province
North Carolina
ZIP/Postal Code
27514
Country
United States

12. IPD Sharing Statement

Citations:
PubMed Identifier
25178924
Citation
Madden MC, Stevens T, Case M, Schmitt M, Diaz-Sanchez D, Bassett M, Montilla TS, Berntsen J, Devlin RB. Diesel exhaust modulates ozone-induced lung function decrements in healthy human volunteers. Part Fibre Toxicol. 2014 Sep 2;11:37. doi: 10.1186/s12989-014-0037-5.
Results Reference
derived

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Cardiopulmonary Responses to Exposure to Ozone and Diesel Exhaust

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