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Macrophage Regulation of Ozone-Induced Lung Inflammation (MOLI)

Primary Purpose

SARS-CoV-2 Pneumonia

Status
Recruiting
Phase
Phase 1
Locations
United States
Study Type
Interventional
Intervention
Ozone
Sponsored by
Robert Tighe, MD
About
Eligibility
Locations
Arms
Outcomes
Full info

About this trial

This is an interventional other trial for SARS-CoV-2 Pneumonia

Eligibility Criteria

18 Years - 55 Years (Adult)All SexesAccepts Healthy Volunteers

Inclusion Criteria: Individuals between 18-55 yrs. of age (No subject will be excluded from the study on the basis of gender or ethnicity) Individuals with knowledge of prior SARS-CoV-2 infection history allowing them to be segregated into one of three cohorts Cohort 1 - No history of SARS-CoV-2 infection (defined as no symptoms consisted with SARS-CoV-2 nor history of a positive SARS-CoV-2 test) Cohort 2 - Documented mild SARS-CoV-2 infection (a positive test, either PCR- or antigen-based) but with mild to no symptoms and no evidence of a lower respiratory tract infection (including no hospitalization, and no oxygen use) Cohort 3 - History of SARS-CoV-2 infection and symptoms/imaging consistent with a lower respiratory tract infection who have recovered, are >6 months out from their infection, and have normal lung function (spirometry with FVC, FEV1 and FEV1/FVC) There will be no maximal period from SARS-CoV-2 infection for inclusion in the study, the minimal period will be >6 months out from infection Exclusion Criteria: Individuals with prior SARS-CoV-2 pneumonia who have ongoing respiratory symptoms, are still using supplemental oxygen, or have abnormal lung function Individuals with prior SARS-CoV-2 infection that cannot provide documentation of a positive test 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 < 4 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.

Sites / Locations

  • Duke University Medical CenterRecruiting

Arms of the Study

Arm 1

Arm 2

Arm 3

Arm Type

Other

Other

Other

Arm Label

Cohort 1

Cohort 2

Cohort 3

Arm Description

No history of SARS-CoV-2

Documented mild SARS-CoV-2 infection

SARS-CoV-2 pneumonia

Outcomes

Primary Outcome Measures

Change in the abundance of monocyte-derived alveolar macrophages
- Change in the abundance of monocyte-derived alveolar macrophages and association to measures of O3-induced inflammation (BAL cell neutrophils, albumin and cytokine production)

Secondary Outcome Measures

Change in the abundance of autonomous CSF-1 expression in alveolar macrophages
- Change in the abundance of autonomous CSF-1 expression in alveolar macrophages and association to measures of O3-induced inflammation
Association between prior evidence of COVID pneumonia
Association between prior evidence of COVID pneumonia, when compared to non-COVID infected individuals, and O3-induced inflammation
Association between prior evidence of COVID infection without pneumonia
Association between prior evidence of COVID infection without pneumonia, when compared to non-COVID infected individuals and O3-induced inflammation

Full Information

First Posted
March 3, 2023
Last Updated
June 28, 2023
Sponsor
Robert Tighe, MD
Collaborators
National Institutes of Health (NIH), National Institute of Environmental Health Sciences (NIEHS)
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1. Study Identification

Unique Protocol Identification Number
NCT05773001
Brief Title
Macrophage Regulation of Ozone-Induced Lung Inflammation
Acronym
MOLI
Official Title
Macrophage Regulation of Ozone-Induced Lung Inflammation
Study Type
Interventional

2. Study Status

Record Verification Date
June 2023
Overall Recruitment Status
Recruiting
Study Start Date
May 18, 2023 (Actual)
Primary Completion Date
May 2028 (Anticipated)
Study Completion Date
May 2028 (Anticipated)

3. Sponsor/Collaborators

Responsible Party, by Official Title
Sponsor-Investigator
Name of the Sponsor
Robert Tighe, MD
Collaborators
National Institutes of Health (NIH), National Institute of Environmental Health Sciences (NIEHS)

4. Oversight

Studies a U.S. FDA-regulated Drug Product
Yes
Studies a U.S. FDA-regulated Device Product
No
Data Monitoring Committee
No

5. Study Description

Brief Summary
The purpose of this research study to understand how prior respiratory infections affect the susceptibility to lung inflammation following environmental exposures.
Detailed Description
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 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.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
SARS-CoV-2 Pneumonia

7. Study Design

Primary Purpose
Other
Study Phase
Phase 1
Interventional Study Model
Crossover Assignment
Masking
Participant
Allocation
Non-Randomized
Enrollment
100 (Anticipated)

8. Arms, Groups, and Interventions

Arm Title
Cohort 1
Arm Type
Other
Arm Description
No history of SARS-CoV-2
Arm Title
Cohort 2
Arm Type
Other
Arm Description
Documented mild SARS-CoV-2 infection
Arm Title
Cohort 3
Arm Type
Other
Arm Description
SARS-CoV-2 pneumonia
Intervention Type
Drug
Intervention Name(s)
Ozone
Other Intervention Name(s)
O3
Intervention Description
Subjects will perform alternating 15 minutes rest with 15 minutes treadmill walk exercise periods for 135 minutes in while breathing Ozone (O3).
Primary Outcome Measure Information:
Title
Change in the abundance of monocyte-derived alveolar macrophages
Description
- Change in the abundance of monocyte-derived alveolar macrophages and association to measures of O3-induced inflammation (BAL cell neutrophils, albumin and cytokine production)
Time Frame
Baseline, Day 18-20
Secondary Outcome Measure Information:
Title
Change in the abundance of autonomous CSF-1 expression in alveolar macrophages
Description
- Change in the abundance of autonomous CSF-1 expression in alveolar macrophages and association to measures of O3-induced inflammation
Time Frame
Baseline, Day 18-20
Title
Association between prior evidence of COVID pneumonia
Description
Association between prior evidence of COVID pneumonia, when compared to non-COVID infected individuals, and O3-induced inflammation
Time Frame
Baseline, Day 18-20
Title
Association between prior evidence of COVID infection without pneumonia
Description
Association between prior evidence of COVID infection without pneumonia, when compared to non-COVID infected individuals and O3-induced inflammation
Time Frame
Baseline, Day 18-20
Other Pre-specified Outcome Measures:
Title
Change in composition of BAL immune cells following O3 exposure
Description
Change in composition of BAL immune cells following O3 exposure will identify unique immune cells driving inflammation and physiologic responses
Time Frame
Baseline, Day 18-20
Title
Comparison between BAL immune cells and immune cells obtained from bronchial brushings
Description
Comparison between BAL immune cells and immune cells obtained from bronchial brushings and the relationship to O3 induced inflammation and physiologic responses
Time Frame
Baseline, Day 18-20
Title
Interactions between airway epithelial cells and immune cells
Description
o Interactions between airway epithelial cells and immune cells by RNA-sequencing to define an "interactome"
Time Frame
Baseline, Day 18-20

10. Eligibility

Sex
All
Minimum Age & Unit of Time
18 Years
Maximum Age & Unit of Time
55 Years
Accepts Healthy Volunteers
Accepts Healthy Volunteers
Eligibility Criteria
Inclusion Criteria: Individuals between 18-55 yrs. of age (No subject will be excluded from the study on the basis of gender or ethnicity) Individuals with knowledge of prior SARS-CoV-2 infection history allowing them to be segregated into one of three cohorts Cohort 1 - No history of SARS-CoV-2 infection (defined as no symptoms consisted with SARS-CoV-2 nor history of a positive SARS-CoV-2 test) Cohort 2 - Documented mild SARS-CoV-2 infection (a positive test, either PCR- or antigen-based) but with mild to no symptoms and no evidence of a lower respiratory tract infection (including no hospitalization, and no oxygen use) Cohort 3 - History of SARS-CoV-2 infection and symptoms/imaging consistent with a lower respiratory tract infection who have recovered, are >6 months out from their infection, and have normal lung function (spirometry with FVC, FEV1 and FEV1/FVC) There will be no maximal period from SARS-CoV-2 infection for inclusion in the study, the minimal period will be >6 months out from infection Exclusion Criteria: Individuals with prior SARS-CoV-2 pneumonia who have ongoing respiratory symptoms, are still using supplemental oxygen, or have abnormal lung function Individuals with prior SARS-CoV-2 infection that cannot provide documentation of a positive test 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 < 4 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.
Central Contact Person:
First Name & Middle Initial & Last Name or Official Title & Degree
Claudia Salazar
Phone
9196602026
Email
claudia.salazar@duke.edu
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Robert Tighe, MD
Organizational Affiliation
Duke University
Official's Role
Principal Investigator
Facility Information:
Facility Name
Duke University Medical Center
City
Durham
State/Province
North Carolina
ZIP/Postal Code
27710
Country
United States
Individual Site Status
Recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Claudia Salazar, BS
Phone
919-660-2026
Email
claudia.salazar@duke.edu
First Name & Middle Initial & Last Name & Degree
Robert Tigher, MD

12. IPD Sharing Statement

Plan to Share IPD
No

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Macrophage Regulation of Ozone-Induced Lung Inflammation

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