Mechanisms of Ozone-Induced Alterations in Efferocytosis and Phagocytosis

NCT ID: NCT03646877

Last Updated: 2024-03-12

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: PHASE1
• Total Enrollment: 22 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2019-03-19
• Study Completion Date: 2023-07-27

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.

Conditions

Healthy

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: CROSSOVER
• Primary Study Purpose: OTHER
• Blinding Strategy: SINGLE

Study Groups

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).

Group Type: EXPERIMENTAL

Ozone

Intervention Type: DRUG

Subjects will perform alternating 15 minutes rest with 15 minutes treadmill walk exercise periods for 135 minutes in while breathing Ozone (O3).

Filtered Air (FA)

Control will be treadmill walk with filtered room air in chamber.

Group Type: PLACEBO_COMPARATOR

Filtered Air

Intervention Type: OTHER

Subjects will perform alternating 15 minutes rest with 15 minutes treadmill walk exercise periods for 135 minutes in while breathing filtered air.

Interventions

Ozone

Subjects will perform alternating 15 minutes rest with 15 minutes treadmill walk exercise periods for 135 minutes in while breathing Ozone (O3).

Intervention Type: DRUG

Filtered Air

Subjects will perform alternating 15 minutes rest with 15 minutes treadmill walk exercise periods for 135 minutes in while breathing filtered air.

Intervention Type: OTHER

Other Intervention Names

O3

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.

• Minimum Eligible Age: 18 Years
• Maximum Eligible Age: 35 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: Yes

Sponsors

National Institutes of Health (NIH)

NIH

Sponsor Role: collaborator

Ohio State University

OTHER

Sponsor Role: collaborator

Robert Tighe, MD

OTHER

Sponsor Role: lead

Responsible Party

Robert Tighe, MD

Associate Professor of Medicine

Responsibility Role: SPONSOR_INVESTIGATOR

Principal Investigators

Robert Tighe, MD

Role: PRINCIPAL_INVESTIGATOR

Duke University

Locations

Duke University Medical Center

Durham, North Carolina, United States

Countries

United States

Other Identifiers

ES028829

Identifier Type: OTHER_GRANT

Identifier Source: secondary_id

PRO00100375

Identifier Type: -

Identifier Source: org_study_id