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| ID | Type | Description | Link |
|---|---|---|---|
| ES028829 | Other Grant/Funding Number | NIH |
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| Name | Class |
|---|---|
| National Institutes of Health (NIH) | NIH |
| Ohio State University | OTHER |
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The purpose of this research study to understand how environmental and genetic factors may be involved in lung function. Healthy Study participants will undergo a 1-day screening that includes a blood draw and breathing testing, return for a two-day series of testing to include blood draw, and brief breathing test before and after an inhaled challenge with either filtered air (FA) or ozone (O3). Participants return the next day for a brief breathing test, a blood draw and a procedure called bronchoscopy performed under conscious sedation to evaluate the lung after the challenge.
Participants then return 18 - 20 days later to repeat the two-day series of testing to be challenged with the exposure not received on the first series, (FA or O3). Each visit will take about 3 - 3.5 hours. Follow-up phone calls from the study team will occur at 24 hours after each 2-day test series. Total study duration is about one to one-and a half months.
In brief, at V1 subjects will be assessed for baseline spirometry and venous blood analysis prior to exposure. The venous blood will be used to obtain PMNs for apoptosis assays, and serum for CFH and sCD163 levels. Additionally, this will be used to measure cytokines and growth factors. At each visit, if the subject is female, there will be a urine pregnancy test performed. Following this initial assessment, subjects will be challenged with FA or O3 and then spirometry will be performed, and venous blood will be obtained immediately following the exposure (V2). The subjects will then return 20 hours ±4h later for follow up studies (V3). There will be spirometry, a venous blood draw and urine pregnancy testing (if female) followed by bronchoscopy. At bronchoscopy, vital signs will be determined, including O2 sat. Patient then undergo an 18-20 day washout period before they are brought back in for V4 for the alternate challenge. This will follow the same protocol as outline above in the initial exposure and use the same series of analysis as the first set of visits. Therefore, we will fully characterize the biological response to ozone and filtered air in these same subjects.
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| Label | Type | Description | Intervention Names |
|---|---|---|---|
| Ozone (O3) | Experimental | The O3 level during the exposures will be 200 ppb, which has previously been used in human exposure studies without short or long term, untoward side effects (and comparable to peak levels attained during the summer in the Raleigh-Durham area of North Carolina) (REF - Bromberg review). |
|
| Filtered Air (FA) | Placebo Comparator | Control will be treadmill walk with filtered room air in chamber. |
|
| Name | Type | Description | Arm Group Labels | Other Names |
|---|---|---|---|---|
| Ozone | Drug | Subjects will perform alternating 15 minutes rest with 15 minutes treadmill walk exercise periods for 135 minutes in while breathing Ozone (O3). |
|
| Measure | Description | Time Frame |
|---|---|---|
| Change in Ozone Induced Efferocytosis of Lung Macrophages (Ability to Clear Dead or Dying Cells) | Efferocytosis is defined by determining the number of apoptotic PMNs phagocytized by alveolar macrophages (BAL cytospins) versus the total number of macrophages ('efferocytic index'). The efferocytic index is a measure of how efficiently macrophages engulf and clear apoptotic (dying) cells. It can be determined by counting the number of macrophages that have a phagocytosed apoptotic body and dividing it by the total number of macrophages counted. A higher value is considered better. | Baseline, 21 days |
| Change in Ozone Induced Phagocytosis of Lung Macrophages (Ability to Clear Debris or Bacteria) | Bronchoalveolar macrophages are incubated with pHrodo™ dye-labeled particles. Macrophage phagocytosis will be defined by determining the number of macrophages that contain fluorescent particles versus the total macrophages. Cell free hemoglobin and soluble CD163 - both are measured by commercial ELISA kit. | Baseline, 21 days |
| Measure | Description | Time Frame |
|---|---|---|
| Change in Ozone Induced Increase in Cell Free Hemoglobin in Bronchoalveolar Lavage Fluid | Measured by spectroscopy. | Baseline, 21 days |
| Change in Ozone Induced Increase in Soluble CD163 in Bronchoalveolar Lavage Fluid |
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Inclusion Criteria
• Individuals between 18-35 yrs. of age (No subject will be excluded from the study on the basis of gender or ethnicity)
Exclusion Criteria
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| Name | Affiliation | Role |
|---|---|---|
| Robert Tighe, MD | Duke University | Principal Investigator |
| Facility | Status | City | State | ZIP | Country | Contacts |
|---|---|---|---|---|---|---|
| Duke University Medical Center | Durham | North Carolina | 27710 | United States |
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Subjects were recruited from Duke University campus and surrounding Durham, NC, community using advertisement in newspapers, mailings, and the campus student newspaper. Subjects were screened to determine eligibility per protocol inclusion and exclusion criteria.
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| ID | Title | Description |
|---|---|---|
| FG000 | Ozone (O3), Then Filtered Air (FA) | The O3 level during the exposures will be 200 ppb, which has previously been used in human exposure studies without short or long term, untoward side effects (and comparable to peak levels attained during the summer in the Raleigh-Durham area of North Carolina). Ozone: Subjects will perform alternating 15 minutes rest with 15 minutes treadmill walk exercise periods for 135 minutes in while breathing Ozone (O3). Control will be treadmill walk with filtered room air in chamber. Filtered Air: Subjects will perform alternating 15 minutes rest with 15 minutes treadmill walk exercise periods for 135 minutes in while breathing filtered air. |
| FG001 | Filtered Air (FA), Then Ozone (O3) | Control will be treadmill walk with filtered room air in chamber. Filtered Air: Subjects will perform alternating 15 minutes rest with 15 minutes treadmill walk exercise periods for 135 minutes in while breathing filtered air. The O3 level during the exposures will be 200 ppb, which has previously been used in human exposure studies without short or long term, untoward side effects (and comparable to peak levels attained during the summer in the Raleigh-Durham area of North Carolina). Ozone: Subjects will perform alternating 15 minutes rest with 15 minutes treadmill walk exercise periods for 135 minutes in while breathing Ozone (O3). |
| Title | Milestones | Reasons Not Completed | ||||||||||||
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Overall Study |
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Participants who completed the study.
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| ID | Title | Description |
|---|---|---|
| BG000 | Ozone (O3) and Filtered Air (FA) | The O3 level during the exposures will be 200 ppb, which has previously been used in human exposure studies without short or long term, untoward side effects (and comparable to peak levels attained during the summer in the Raleigh-Durham area of North Carolina) (REF - Bromberg review). Ozone: Subjects will perform alternating 15 minutes rest with 15 minutes treadmill walk exercise periods for 135 minutes in while breathing Ozone (O3). Control will be treadmill walk with filtered room air in chamber. Filtered Air: Subjects will perform alternating 15 minutes rest with 15 minutes treadmill walk exercise periods for 135 minutes in while breathing filtered air. |
| Units | Counts |
|---|---|
| Participants |
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| Title | Description | Population Description | Parameter Type | Dispersion Type | Unit of Measure | Calculate Percentage | Denominator Units Selected | Denominators | Classes |
|---|---|---|---|---|---|---|---|---|---|
| Age, Continuous | Mean |
| Type | Title | Description | Population Description | Reporting Status | Anticipated Posting Date | Parameter Type | Dispersion Type | Unit of Measure | Calculate Percentage | Time Frame | Units Analyzed | Denominator Units Selected | Arm/Group Information | Denominators | Classes | Analyses | |||
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Primary | Change in Ozone Induced Efferocytosis of Lung Macrophages (Ability to Clear Dead or Dying Cells) | Efferocytosis is defined by determining the number of apoptotic PMNs phagocytized by alveolar macrophages (BAL cytospins) versus the total number of macrophages ('efferocytic index'). The efferocytic index is a measure of how efficiently macrophages engulf and clear apoptotic (dying) cells. It can be determined by counting the number of macrophages that have a phagocytosed apoptotic body and dividing it by the total number of macrophages counted. A higher value is considered better. | Participants with complete data sets for both O3 and FA. | Posted | Mean | Standard Deviation | ratio | Baseline, 21 days |
|
Up to 21 days
All participants received both interventions.
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| ID | Title | Description | Deaths (Affected) | Deaths (At Risk) | Serious Events (Affected) | Serious Events (At Risk) | Other Events (Affected) | Other Events (At Risk) |
|---|---|---|---|---|---|---|---|---|
| EG000 | Ozone (O3) | The O3 level during the exposures will be 200 ppb, which has previously been used in human exposure studies without short or long term, untoward side effects (and comparable to peak levels attained during the summer in the Raleigh-Durham area of North Carolina) (REF - Bromberg review). Ozone: Subjects will perform alternating 15 minutes rest with 15 minutes treadmill walk exercise periods for 135 minutes in while breathing Ozone (O3). |
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| Term | Organ System | Source Vocabulary | Assessment Type | Notes | Statistical Information |
|---|---|---|---|---|---|
| Near syncope | Nervous system disorders | Systematic Assessment |
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| Title | Organization | Phone | Extension | |
|---|---|---|---|---|
| Robert Tighe, MD | Duke University | 919-684-4894 | robert.tighe@duke.edu |
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| Type | Includes Protocol | Includes SAP | Includes ICF | Document Label | Document Date | Document Uploaded Date | Document File Name |
|---|---|---|---|---|---|---|---|
| Prot_SAP | Yes | Yes | No | Study Protocol and Statistical Analysis Plan | Dec 13, 2021 | Jul 22, 2024 | Prot_SAP_000.pdf |
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| ID | Term |
|---|---|
| D010126 | Ozone |
| ID | Term |
|---|---|
| D010100 | Oxygen |
| D005740 | Gases |
| D007287 | Inorganic Chemicals |
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| Filtered Air | Other | Subjects will perform alternating 15 minutes rest with 15 minutes treadmill walk exercise periods for 135 minutes in while breathing filtered air. |
|
Measured by enzyme-linked immunosorbent assay (ELISA)
| Baseline, 21 days |
| years |
|
| Sex: Female, Male | Count of Participants | Participants |
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| Ethnicity (NIH/OMB) | Count of Participants | Participants |
|
| Race (NIH/OMB) | Count of Participants | Participants |
|
| Region of Enrollment | Count of Participants | Participants |
|
| OG001 | Filtered Air (FA) | Control will be treadmill walk with filtered room air in chamber. Filtered Air: Subjects will perform alternating 15 minutes rest with 15 minutes treadmill walk exercise periods for 135 minutes in while breathing filtered air. |
|
|
|
| Primary | Change in Ozone Induced Phagocytosis of Lung Macrophages (Ability to Clear Debris or Bacteria) | Bronchoalveolar macrophages are incubated with pHrodo™ dye-labeled particles. Macrophage phagocytosis will be defined by determining the number of macrophages that contain fluorescent particles versus the total macrophages. Cell free hemoglobin and soluble CD163 - both are measured by commercial ELISA kit. | Data not collected. | Posted | Baseline, 21 days |
|
|
| Secondary | Change in Ozone Induced Increase in Cell Free Hemoglobin in Bronchoalveolar Lavage Fluid | Measured by spectroscopy. | Participants with complete data sets for both O3 and FA. | Posted | Mean | Standard Deviation | micromolar (uM) | Baseline, 21 days |
|
|
|
|
| Secondary | Change in Ozone Induced Increase in Soluble CD163 in Bronchoalveolar Lavage Fluid | Measured by enzyme-linked immunosorbent assay (ELISA) | Participants with complete data sets for both O3 and FA. | Posted | Mean | Standard Deviation | ng/mL | Baseline, 21 days |
|
|
|
|
| 0 |
| 35 |
| 0 |
| 35 |
| 1 |
| 35 |
| EG001 | Filtered Air (FA) | Control will be treadmill walk with filtered room air in chamber. Filtered Air: Subjects will perform alternating 15 minutes rest with 15 minutes treadmill walk exercise periods for 135 minutes in while breathing filtered air. | 0 | 35 | 0 | 35 | 0 | 35 |
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