Mechanisms of Ozone-Induced Alterations in Efferocytosis and Phagocytosis

NCT03646877 | Completed Phase 1 DMC FDA Drug

• 2 other identifiers: PRO00100375ES028829
• Study Type: interventional
• Target: 22
• Locations: 1 country
• Sites: 1

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.

Conditions

Healthy

Outcome Measures

Primary Outcomes (2)

• 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')

  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

Secondary Outcomes (2)

• Change in ozone induced increase in cell free hemoglobin in bronchoalveolar lavage fluid and serum

  Baseline, 21 days

• Change in ozone induced increase in soluble CD163 in bronchoalveolar lavage fluid and serum

  Baseline, 21 days

Study Arms (2)

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).

Drug: Ozone

Filtered Air (FA)

PLACEBO COMPARATOR

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

Other: Filtered Air

Interventions

Ozone DRUG

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

Also known as: O3

Ozone (O3)

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.

Filtered Air (FA)

Eligibility Criteria

• Age: 18 Years - 35 Years
• Sex: all
• Healthy Volunteers: Yes
• Age Groups: Adult (18-64)

You may qualify if:

• Individuals between 18-35 yrs. of age (No subject will be excluded from the study on the basis of gender or ethnicity)

You may not qualify if:

• 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.

Sponsors & Collaborators

• Robert Tighe, MD: lead
• National Institutes of Health (NIH): collaborator
• Ohio State University: collaborator

Study Sites (1)

Duke University Medical Center

Durham, North Carolina, 27710, United States

Location

MeSH Terms

Interventions

Ozone

Intervention Hierarchy (Ancestors)

Oxygen; Gases; Inorganic Chemicals

Study Officials

• Robert Tighe, MD

  Duke University

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: RANDOMIZED
• Masking: SINGLE
• Who Masked: PARTICIPANT
• Purpose: OTHER
• Intervention Model: CROSSOVER
• Sponsor Type: OTHER
• Responsible Party: SPONSOR INVESTIGATOR
• PI Title: Associate Professor of Medicine

Study Record Dates

• First Submitted: August 23, 2018
• First Posted: August 24, 2018
• Study Start: March 19, 2019
• Primary Completion: July 26, 2023
• Study Completion: July 27, 2023
• Last Updated: March 12, 2024

Record last verified: 2024-03

Data Sharing

• IPD Sharing: Will not share

Locations

US (1)