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Pulmonary and Inflammatory Responses Following Exposure to a Low Concentration of Ozone or Clean Air (LOCONOZ2)

Primary Purpose

Lung Injury, Acute, Symptoms and Signs, Neutrophilia Acute

Status
Recruiting
Phase
Phase 1
Locations
United States
Study Type
Interventional
Intervention
0.070 ppm ozone concentration
Clean air (0.0 ppm ozone)
Sponsored by
Martin W. Case
About
Eligibility
Locations
Arms
Outcomes
Full info

About this trial

This is an interventional basic science trial for Lung Injury, Acute focused on measuring lungs, ozone concentration, exercise, inflammation, symptoms

Eligibility Criteria

18 Years - 35 Years (Adult)All SexesAccepts Healthy Volunteers

Inclusion Criteria: Healthy men and women between 18 and 35 years of age. Physical conditions allowing sustained moderate exercise for 6.6 hours. Normal lung function (NHANES III): FVC > 80 % of that predicted for gender, ethnicity, age and height. FEV1 > 80 % of that predicted for gender, ethnicity, age and height. FEV1/FVC ratio > 80 % of predicted values Oxygen saturation > 94 %. Total symptom Score no greater than 20 (out of a possible 60-see accompanying score sheet) with a value no greater than 3 for any one score. No more than one score may be equal to 3. Exclusion Criteria: Individuals with a diagnosis of COVID-19 and/or hospitalized for COVID-19. Individuals who are not "up to date," [meaning a person has received all recommended COVID-19 vaccines, including any booster dose(s) when eligible with their COVID vaccines as defined by the CDC.] A history of acute and chronic cardiovascular disease, chronic respiratory disease, diabetes,rheumatologic diseases, immunodeficiency state. An 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 currently taking mega doses of vitamins and supplements, homeopathic/naturopathic medicines or medications which may impact the results of the ozone challenge or interfere with any other medications potentially used in the study (to include systemic steroids and beta blockers). 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 2 years, or subjects with a smoking history of at least a pack of cigarettes a day for more than 10 years over your lifetime. This includes vaping, hookah,and e-cigarettes. Uncontrolled hypertension (> 140 systolic, > 90 diastolic). Blood pressure readings equal to or greater that 140 Systolic and equal to or greater that 90 diastolic. Subjects who do not understand or speak English Unspecified illnesses, which in the judgment of the investigator might increase the risk associated with ozone inhalation challenge or exercise, will be a basis for exclusion. Temporary exclusion criteria: Individuals who have had an acute respiratory illness within 4 weeks. Individuals who have active allergies. Individuals that have engaged in strenuous exercise within 24 hours of any study visit. Individuals unable to avoid drinking alcohol for 24 hours prior to all study visits. Individuals who have been exposed to smoke and fumes for 24 hours before all visits. Individuals that have used an ozone-based home air purifier for 24 hours before all visits. Individuals that have eaten or drank anything for 2 hours prior to the sputum training/screening day visit. Individuals should avoid caffeine for 12 hours prior to all study visits. Individuals should refrain from all over the counter anti-inflammatory agents including those for allergies, and anti-inflammatory drugs or antioxidants for a period of one week prior to the train and to the exposure. Individuals that have been exposed to or have consumed any agent or have undertaken any activity within 24 hours of any study visit that the investigators believe may compromise the results of the study. -

Sites / Locations

  • EPA Human Studies FacilityRecruiting

Arms of the Study

Arm 1

Arm 2

Arm Type

Experimental

Experimental

Arm Label

0.070 ppm ozone concentration

Clean air (0.0 ppm ozone)

Arm Description

Exposure to 0.070 ppm ozone for 6.6 hours while performing moderate intermittent exercise.

Exposure to clean air (0.0 ppm ozone) for 6.6 hours while performing moderate intermittent exercise.

Outcomes

Primary Outcome Measures

FVC
forced vital capacity
Change in FVC
change in forced vital capacity
FEV1
forced expiratory volume in 1 second
Change in FEV1
change in forced expiratory volume in 1 second

Secondary Outcome Measures

% neutrophils collected by induced sputum
Subjects will breathe a hypertonic saline solution from an ultrasonic nebulizer through a mouthpiece at saline concentrations of 3%, 4%, and 5%. After each inhalation period subjects be asked to cough up the expectorate in a sterile cup for analysis of neutrophil cells influx
change in % neutrophils collected by induced sputum
Subjects will breathe a hypertonic saline solution from an ultrasonic nebulizer through a mouthpiece at saline concentrations of 3%, 4%, and 5%. After each inhalation period subjects be asked to cough up the expectorate in a sterile cup for analysis/quantitation of neutrophil cells influx

Full Information

First Posted
December 16, 2022
Last Updated
January 9, 2023
Sponsor
Martin W. Case
Collaborators
University of North Carolina
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1. Study Identification

Unique Protocol Identification Number
NCT05680831
Brief Title
Pulmonary and Inflammatory Responses Following Exposure to a Low Concentration of Ozone or Clean Air
Acronym
LOCONOZ2
Official Title
Pulmonary and Inflammatory Responses Following Exposure to a Low Concentration of Ozone or Clean Air for 6.6 Hours With Moderate Exercise in Healthy Young Adults
Study Type
Interventional

2. Study Status

Record Verification Date
January 2023
Overall Recruitment Status
Recruiting
Study Start Date
October 13, 2022 (Actual)
Primary Completion Date
February 1, 2024 (Anticipated)
Study Completion Date
February 1, 2025 (Anticipated)

3. Sponsor/Collaborators

Responsible Party, by Official Title
Sponsor-Investigator
Name of the Sponsor
Martin W. Case
Collaborators
University of North Carolina

4. Oversight

Studies a U.S. FDA-regulated Drug Product
Yes
Studies a U.S. FDA-regulated Device Product
No
Data Monitoring Committee
No

5. Study Description

Brief Summary
Purpose: The primary purpose of this study is to measure pulmonary function, symptoms, and pulmonary inflammatory responses in healthy young adults during and immediately after exposure to a low concentration of ozone (0.070 ppm) or clean air for 6.6 hours while undergoing moderate intermittent exercise. This concentration is the current EPA NAAQS standard for ozone.
Detailed Description
Potential health effects of ozone have been extensively studied over decades at various levels of exposure concentration and for varying time periods in young healthy adult subjects. Effects of ozone have been well documented particularly for decrements of lung function and an influx of neutrophils and other markers of pulmonary inflammation. The majority of those studies were done at ozone concentrations between 0.12 and 0.40 ppm, considerably higher than the current EPA NAAQS ozone standard of 0.070 ppm, and at exposure durations of two hours, even though the current standard is an 8-hour standard. However, a small number of studies have assessed changes in lung function following exposure to low levels of ozone for several hours. These latter studies have shown that exposure to ozone for 6.6 hours at concentrations between 0.06 and 0.08 ppm causes mild reversible decrements in lung function (1.7-10%) as measured by forced vital capacity (FVC) and forced expired volume at 1 s (FEV1) immediately after exposure in healthy young adults. In addition, in one study an increase in ozone-induced neutrophils was seen in induced sputum following exposure to 0.06 ppm ozone (8) and in bronchoalveolar lavage fluid) following exposure to 0.08 ppm ozone (9). The EPA is considering whether the current ozone NAAQS standard at 0.070 is protective and has asked EPA researchers to conduct a study similar to those done at 0.06 and 0.08 ppm.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Lung Injury, Acute, Symptoms and Signs, Neutrophilia Acute
Keywords
lungs, ozone concentration, exercise, inflammation, symptoms

7. Study Design

Primary Purpose
Basic Science
Study Phase
Phase 1
Interventional Study Model
Crossover Assignment
Model Description
This is a randomized, double-blind, cross-over study with two arms.
Masking
ParticipantCare ProviderInvestigatorOutcomes Assessor
Masking Description
TRC Environmental Corporation, who is on-site contractor responsible for the exposure operation will randomize the subjects into either air or ozone arms, neither subjects nor staff involved in conduct of experiments will be informed of exposure conditions.
Allocation
Randomized
Enrollment
60 (Anticipated)

8. Arms, Groups, and Interventions

Arm Title
0.070 ppm ozone concentration
Arm Type
Experimental
Arm Description
Exposure to 0.070 ppm ozone for 6.6 hours while performing moderate intermittent exercise.
Arm Title
Clean air (0.0 ppm ozone)
Arm Type
Experimental
Arm Description
Exposure to clean air (0.0 ppm ozone) for 6.6 hours while performing moderate intermittent exercise.
Intervention Type
Biological
Intervention Name(s)
0.070 ppm ozone concentration
Intervention Description
The concentration of ozone a subject will randomly receive on a visit for 6.6 hours in a controlled atmospheric chamber while performing moderate intermittent exercise.
Intervention Type
Biological
Intervention Name(s)
Clean air (0.0 ppm ozone)
Intervention Description
Same subject will randomly receive clean air on another visit separated by at least one week for 6.6 hours in the same controlled atmospheric chamber while performing moderate intermittent exercise.
Primary Outcome Measure Information:
Title
FVC
Description
forced vital capacity
Time Frame
measured (pre) before starting 6.6 hours of exercise
Title
Change in FVC
Description
change in forced vital capacity
Time Frame
change measured (post) immediately after 6.6 hours of exercise
Title
FEV1
Description
forced expiratory volume in 1 second
Time Frame
measured (pre) before starting 6.6 hours of exercise
Title
Change in FEV1
Description
change in forced expiratory volume in 1 second
Time Frame
change measured (post) immediately after 6.6 hours of exercise
Secondary Outcome Measure Information:
Title
% neutrophils collected by induced sputum
Description
Subjects will breathe a hypertonic saline solution from an ultrasonic nebulizer through a mouthpiece at saline concentrations of 3%, 4%, and 5%. After each inhalation period subjects be asked to cough up the expectorate in a sterile cup for analysis of neutrophil cells influx
Time Frame
baseline: training/qualification day
Title
change in % neutrophils collected by induced sputum
Description
Subjects will breathe a hypertonic saline solution from an ultrasonic nebulizer through a mouthpiece at saline concentrations of 3%, 4%, and 5%. After each inhalation period subjects be asked to cough up the expectorate in a sterile cup for analysis/quantitation of neutrophil cells influx
Time Frame
18 hours post exposure

10. Eligibility

Sex
All
Minimum Age & Unit of Time
18 Years
Maximum Age & Unit of Time
35 Years
Accepts Healthy Volunteers
Accepts Healthy Volunteers
Eligibility Criteria
Inclusion Criteria: Healthy men and women between 18 and 35 years of age. Physical conditions allowing sustained moderate exercise for 6.6 hours. Normal lung function (NHANES III): FVC > 80 % of that predicted for gender, ethnicity, age and height. FEV1 > 80 % of that predicted for gender, ethnicity, age and height. FEV1/FVC ratio > 80 % of predicted values Oxygen saturation > 94 %. Total symptom Score no greater than 20 (out of a possible 60-see accompanying score sheet) with a value no greater than 3 for any one score. No more than one score may be equal to 3. Exclusion Criteria: Individuals with a diagnosis of COVID-19 and/or hospitalized for COVID-19. Individuals who are not "up to date," [meaning a person has received all recommended COVID-19 vaccines, including any booster dose(s) when eligible with their COVID vaccines as defined by the CDC.] A history of acute and chronic cardiovascular disease, chronic respiratory disease, diabetes,rheumatologic diseases, immunodeficiency state. An 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 currently taking mega doses of vitamins and supplements, homeopathic/naturopathic medicines or medications which may impact the results of the ozone challenge or interfere with any other medications potentially used in the study (to include systemic steroids and beta blockers). 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 2 years, or subjects with a smoking history of at least a pack of cigarettes a day for more than 10 years over your lifetime. This includes vaping, hookah,and e-cigarettes. Uncontrolled hypertension (> 140 systolic, > 90 diastolic). Blood pressure readings equal to or greater that 140 Systolic and equal to or greater that 90 diastolic. Subjects who do not understand or speak English Unspecified illnesses, which in the judgment of the investigator might increase the risk associated with ozone inhalation challenge or exercise, will be a basis for exclusion. Temporary exclusion criteria: Individuals who have had an acute respiratory illness within 4 weeks. Individuals who have active allergies. Individuals that have engaged in strenuous exercise within 24 hours of any study visit. Individuals unable to avoid drinking alcohol for 24 hours prior to all study visits. Individuals who have been exposed to smoke and fumes for 24 hours before all visits. Individuals that have used an ozone-based home air purifier for 24 hours before all visits. Individuals that have eaten or drank anything for 2 hours prior to the sputum training/screening day visit. Individuals should avoid caffeine for 12 hours prior to all study visits. Individuals should refrain from all over the counter anti-inflammatory agents including those for allergies, and anti-inflammatory drugs or antioxidants for a period of one week prior to the train and to the exposure. Individuals that have been exposed to or have consumed any agent or have undertaken any activity within 24 hours of any study visit that the investigators believe may compromise the results of the study. -
Central Contact Person:
First Name & Middle Initial & Last Name or Official Title & Degree
Martin W Case, B.S.
Phone
919-966-6211
Email
case.martin@epa.gov
First Name & Middle Initial & Last Name or Official Title & Degree
Andrea Davis, R.N.
Phone
919-966-6241
Email
davis.andrea@epa.gov
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Andy Ghio, M.D.
Organizational Affiliation
EPA/ORD/CPHEA/PHITD/CRB
Official's Role
Principal Investigator
Facility Information:
Facility Name
EPA Human Studies Facility
City
Chapel Hill
State/Province
North Carolina
ZIP/Postal Code
27599-7315
Country
United States
Individual Site Status
Recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Al Little
Phone
919-966-5884
Email
little.al@epa.gov
First Name & Middle Initial & Last Name & Degree
Ana Rappold, Ph.D.

12. IPD Sharing Statement

Plan to Share IPD
No

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Pulmonary and Inflammatory Responses Following Exposure to a Low Concentration of Ozone or Clean Air

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