Clinical trial NCT03646877: Mechanisms of Ozone-Induced Alterations in Efferocytosis and Phagocytosis
Official title: Mechanisms of Ozone-Induced Alterations in Efferocytosis and Phagocytosis
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE1
Conditions: Healthy
Lead sponsor: Duke University
Sponsor class: OTHER
Collaborators: name: National Institutes of Health (NIH)
name: Ohio State University
First posted: 2018-08-24
Enrollment: 22
Sex: ALL
Minimum age (years): 18
Maximum age (years): 35
Standard ages: ADULT
Accepts healthy volunteers: yes
Allocation: RANDOMIZED
Intervention model: CROSSOVER
Primary purpose: OTHER

Brief summary: 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.

Detailed description: 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.

Eligibility criteria: 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

* Current smokers of tobacco products including e-cigarettes or those with previous smoking history within the prior 5 years
* Pregnant women and women who are presently lactating.
* Subjects that have received antibiotic administration or an upper respiratory infection within the previous 4 weeks
* College and graduate students or employees who are under direct supervision by any of the investigators in this protocol
* Alcohol or illicit substance abuse
* Chronic cardio/pulmonary respiratory disorders or other medical conditions as determined by the investigator
* Increased airway hyperresponsiveness at baseline as measured by a positive methacholine challenge response (methacholine PC20 FEV1 \< 8 mg/ml)
* Subjects will be requested to refrain from antihistamines, nonsteroidal anti-inflammatory agents, antioxidants (e.g. beta-carotene, selenium, and lutein) and supplemental vitamins (e.g. C and E), for 1 week prior to, and during testing.

Primary outcomes:
measure: change in ozone induced efferocytosis of lung macrophages (ability to clear dead or dying cells)
timeFrame: Baseline, 21 days
measure: Change in ozone induced phagocytosis of lung macrophages (ability to clear debris or bacteria)
timeFrame: Baseline, 21 days
Secondary outcomes:
measure: Change in ozone induced increase in cell free hemoglobin in bronchoalveolar lavage fluid and serum
timeFrame: Baseline, 21 days
measure: Change in ozone induced increase in soluble CD163 in bronchoalveolar lavage fluid and serum
timeFrame: Baseline, 21 days
Other outcomes:
Locations:
city: Durham
country: United States
facility: Duke University Medical Center
state: North Carolina
Study officials:
affiliation: Duke University
name: Robert Tighe, MD
role: PRINCIPAL_INVESTIGATOR
References: