Lung Injury, AcutePhase 1LOCONOZ2NCT05680831
Pulmonary and Inflammatory Responses Following Exposure to a Low Concentration of Ozone or Clean Air
A Phase 1 study testing 0.070 ppm ozone concentration and Clean air (0.0 ppm ozone) in people with Lung Injury, Acute and Symptoms and Signs, run by Martin W. Case at 1 site in United States.
Trial 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. Read more about this study
- Who is it for?
- Ages 18 to 35 yearsHealthy volunteers can take part
- Conditions the study is for
- Lung Injury, Acute, Symptoms and Signs, Neutrophilia Acute
- What is being tested?
- 0.070 ppm ozone concentration and Clean air (0.0 ppm ozone)
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 60 participants
- Where
- 1 siteUnited States
- Study dates
- 13 Oct 2022to 1 Feb 2025
- Phase
- Phase 1
- Are there results?
- None posted in the registry
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 to 35 years
- All sexes
- Healthy volunteers accepted
- Adult
Who may be able to join
- 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.
Who cannot join
- 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.
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- 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.
- -
Trial locations and contacts
1 site in 1 country.
United States1 site, 1 recruiting
- Recruiting
EPA Human Studies Facility
Chapel Hill, North Carolina, 27599-7315
Al Little, 919-966-5884, little.al@epa.gov
Ana Rappold, Ph.D.
About this study
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
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.
Read the 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.
- Conditions
- Lung Injury, Acute, Symptoms and Signs, Neutrophilia Acute
- Being tested
- 0.070 ppm ozone concentration, Clean air (0.0 ppm ozone)
- Keywords
- lungs, ozone concentration, exercise, inflammation, symptoms
- Medical subject headings
- Acute Lung Injury, Signs and Symptoms, Motor Activity, Inflammation
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
0.070 ppm ozone concentrationBiological
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.
Clean air (0.0 ppm ozone)Biological
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.
| Study group | Role | What they receive |
|---|---|---|
| 0.070 ppm ozone concentration | Experimental | Exposure to 0.070 ppm ozone for 6.6 hours while performing moderate intermittent exercise. Receives: Biological: 0.070 ppm ozone concentration |
| Clean air (0.0 ppm ozone) | Experimental | Exposure to clean air (0.0 ppm ozone) for 6.6 hours while performing moderate intermittent exercise. Receives: Biological: Clean air (0.0 ppm ozone) |
What is being measured
The primary outcome is the main question the study is designed to answer.
FVC
forced vital capacity
Measured: measured (pre) before starting 6.6 hours of exercise
Change in FVC
change in forced vital capacity
Measured: change measured (post) immediately after 6.6 hours of exercise
FEV1
forced expiratory volume in 1 second
Measured: measured (pre) before starting 6.6 hours of exercise
Change in FEV1
change in forced expiratory volume in 1 second
Measured: change measured (post) immediately after 6.6 hours of exercise
Secondary outcomes (2)
% 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
Measured: baseline: training/qualification day
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
Measured: 18 hours post exposure
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted11 Jan 2023
- Study start13 Oct 2022
- Primary completion1 Feb 2024 (estimated)
- Study completion1 Feb 2025 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Lung Injury, AcuteStudies of the same condition, open and under way.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 1
- Primary purpose
- Basic science
- Allocation
- Randomised
- Intervention model
- Crossover
- Model description
- This is a randomized, double-blind, cross-over study with two arms.
- Masking
- Quadruple blind
- Who is masked
- Participant, Care provider, Investigator, Outcomes assessor
- Enrolment
- 60 participants (estimated)
Sponsor and investigators
- Lead sponsor
- Martin W. Case
- Sponsor type
- US federal agency
- Collaborators
- University of North Carolina
- Responsible party
- Sponsor-investigator, Martin W. Case, Environmental Protection Agency (EPA)
- Investigators
- Andy Ghio, M.D., Principal investigator, EPA/ORD/CPHEA/PHITD/CRB
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT05680831
- Sponsor's protocol ID
- IRB# 21-3193
- Acronym
- LOCONOZ2
- Status last verified
- Jan 2023
- First submitted
- 16 Dec 2022
- Last updated
- 11 Jan 2023
- Results posted
- No
- Data monitoring committee
- No
- FDA-regulated drug
- Yes
- FDA-regulated device
- No
- Individual data sharing
- No
Study at a glance
From the registry record, last updated by the sponsor on 11 Jan 2023. Recruitment status is as the sponsor reported it: confirm with the study team.
- 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
- ClinicalTrials.gov ID
- NCT05680831
- Acronym / sponsor ID
- LOCONOZ2 / IRB# 21-3193
- Conditions
- Lung Injury, Acute, Symptoms and Signs, Neutrophilia Acute
- Keywords
- lungs, ozone concentration, exercise, inflammation, symptoms
- Phase
- Phase 1
- Study type
- Interventional
- Recruitment status
- Unknown status
- Enrolment
- 60 participants (estimated)
- Lead sponsor
- Martin W. CaseUS federal agency
- Collaborators
- University of North Carolina
- Study start
- 13 Oct 2022 (actual)
- Primary completion
- 1 Feb 2024 (estimated)
- Study completion
- 1 Feb 2025 (estimated)
- First posted
- 11 Jan 2023 (actual)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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.
Study design
- Primary purpose
- Basic science
- Allocation
- Randomised
- Intervention model
- Crossover
- Masking
- Quadruple blind (participant, care provider, investigator, outcomes assessor)
- Number of arms
- 2
- Model description
- This is a randomized, double-blind, cross-over study with two arms.
| Arm | Type | Receives |
|---|---|---|
| 0.070 ppm ozone concentration | Experimental | Biological: 0.070 ppm ozone concentrationExposure to 0.070 ppm ozone for 6.6 hours while performing moderate intermittent exercise. |
| Clean air (0.0 ppm ozone) | Experimental | Biological: Clean air (0.0 ppm ozone)Exposure to clean air (0.0 ppm ozone) for 6.6 hours while performing moderate intermittent exercise. |
Who may qualify
- Ages
- 18 to 35 years
- Sex
- All
- Healthy volunteers
- Accepted
- Age groups
- Adult
Key inclusion criteria (8 listed)
- 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):
- 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.
Key exclusion criteria (25 listed)
- 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.
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| 0.070 ppm ozone concentrationThe 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. | Biological | 0.070 ppm ozone concentration |
| Clean air (0.0 ppm ozone)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. | Biological | Clean air (0.0 ppm ozone) |
Primary outcome
FVC
Time frame: measured (pre) before starting 6.6 hours of exercise
forced vital capacity
Change in FVC
Time frame: change measured (post) immediately after 6.6 hours of exercise
change in forced vital capacity
FEV1
Time frame: measured (pre) before starting 6.6 hours of exercise
forced expiratory volume in 1 second
Change in FEV1
Time frame: change measured (post) immediately after 6.6 hours of exercise
change in forced expiratory volume in 1 second
2 secondary outcomes
% neutrophils collected by induced sputum
Time frame: baseline: training/qualification day
change in % neutrophils collected by induced sputum
Time frame: 18 hours post exposure
Results and safety
Results are not available in the source record.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 11 Jan 2023.
- Individual participant dataSharing planned: No
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Andy Ghio, M.D. principal investigator
EPA/ORD/CPHEA/PHITD/CRB
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 1 study testing 0.070 ppm ozone concentration and Clean air (0.0 ppm ozone) in people with Lung Injury, Acute and Symptoms and Signs, run by Martin W. Case at 1 site in United States.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 8 inclusion and 25 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: status not confirmed, as of the sponsor's last update on 11 Jan 2023. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in United States. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 1 studies test a treatment in a small group of people for the first time or in a new way, mainly to check safety and find the right dose.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
Results are not available in the source record.
How can a doctor refer a patient or contact the research team?
Contact Martin W Case, B.S. (919-966-6211, case.martin@epa.gov), or a site near the patient. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
FVC (time frame: measured (pre) before starting 6.6 hours of exercise). The study lists 4 primary outcomes in all. It is what the study was designed to measure, not a finding.
Where can I read the original study information?
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 11 Jan 2023.