Air Pollution and Inhaled Corticosteroids in COPD

NCT06552364 | Not Yet Recruiting Phase 4

• 1 other identifier: H22-03008
• Study Type: interventional
• Target: 48
• Locations: 0 countries
• Sites: N/A

Brief Summary

Studies have shown that people with chronic obstructive pulmonary disease (COPD) have worse symptoms after breathing polluted air. People with COPD also often need to go to the hospital if they get a virus or other bug. One of the main drugs taken for COPD treatment (inhaled corticosteroid) may change COPD patients' lungs in ways that make it harder to deal with bugs, especially if they breathe in polluted air. If so, this could cause more frequent hospital visits. On the other hand, the same drug (inhaled corticosteroid) helps some people control symptoms, and may help them avoid hospital visits. The APEL investigators are conducting this study (APIC) to understand if this drug (inhaled corticosteroid), in combination with polluted air, will change the lungs of those with COPD in ways that make it more likely to catch bugs or have other problems.

Conditions

COPD

Keywords

Air Pollution; Inhaled Corticosteroid; LABA/LAMA; Triple Therapy (LABA/LAMA/ICS)

Outcome Measures

Primary Outcomes (6)

• Inhaled corticosteroid (ICS) and/or diesel exhaust exposure effects on inflammatory cells.

  Differentially count lung cells.

  Comparison of the different arms over the span of 5 months.

• Inhaled corticosteroid (ICS) and/or diesel exhaust exposure effects on exhaled nitric oxide.

  Measurement of fractional exhaled nitric oxide (FeNO).

  Comparison of the different arms over the span of 5 months.

• Inhaled corticosteroid (ICS) and/or diesel exhaust exposure effects on anti-microbial host defense proteins.

  Anti-microbial host defense (AMP) matrix, determined from, for example, human neutrophil peptide 1 (HNP1; DEFA1), calprotectin (S100A8/S100A9), cathelicidin antimicrobial peptide/LL-37, Lipocalin-2 (LCN2), and S100 calcium-binding protein A7 (S100A7) in the lungs. And dermcidin (DCD), calprotectin (S100A8/S100A9), cathelicidin antimicrobial peptide/LL-37, and amphiregulin (AREG) in peripheral blood.

  Comparison of the different arms over the span of 5 months.

• Inhaled corticosteroid (ICS) and/or diesel exhaust exposure effects on oxidative stress in the lungs.

  Determine oxidative stress (e.g. H2DCFDA) in the lungs.

  Comparison of the different arms over the span of 5 months.

• Inhaled corticosteroid (ICS) and/or diesel exhaust exposure effects on neutrophil extracellular TRAPs (NETs).

  Analysis of counts of neutrophil extracellular TRAPs (NETs).

  Comparison of the different arms over the span of 5 months.

• Inhaled corticosteroid (ICS) and/or diesel exhaust exposure effects on lung inflammatory markers.

  An inflammation matrix will be generated, including data from RNA and proteins (e.g. serum amyloid A (SAA), c-reactive protein (CRP), chemokine ligand 18 (CCL18) and fibrinogen), in the lungs.

  Comparison of the different arms over the span of 5 months.

Secondary Outcomes (10)

• Inhaled corticosteroids (ICS) and/or diesel exhaust exposure induced modulation of circulating markers of inflammation.

  Comparison of the different arms over the span of 5 months.

• Inhaled corticosteroid (ICS) and/or diesel exhaust exposure induced modulation of circulating cells and inflammatory cellular markers.

  Comparison of the different arms over the span of 5 months.

• Inhaled corticosteroid (ICS) and/or diesel exhaust exposure induced modulation of lung resistance as assessed by oscillometry.

  Comparison of the different arms over the span of 5 months.

• Inhaled corticosteroid (ICS) and/or diesel exhaust exposure effects on lung function.

  Comparison of the different arms over the span of 5 months.

• Effects of inhaled corticosteroids (ICS) and/or diesel exhaust on neutrophil function.

  Comparison of the different arms over the span of 5 months.

Study Arms (4)

Filtered Air with LABA/LAMA

PLACEBO COMPARATOR

Participants will inhale a ultra Long-Acting Beta-Agonist (LABA; vilanterol (25mcg)) + Long-acting Muscarinic Antagonist (LAMA; umeclidinium (62.5mcg)) combination medication once daily for 28+ days before sitting in a booth and being exposed to high-efficiency particulate air (HEPA) filtered air for 2 hours.

Drug: LABA+LAMA; Other: Filtered Air

Filtered Air with LABA/LAMA + ICS

ACTIVE COMPARATOR

Participants will inhale a LABA (vilanterol (25mcg)) + LAMA (umeclidinium (62.5mcg))+ Inhaled Corticosteroid (ICS; fluticasone furoate (100mcg)) medication once daily for 28+ days before sitting in a booth and being exposed to HEPA-filtered air for 2 hours.

Drug: LABA+LAMA+ICS; Other: Filtered Air

Diesel Exhaust with LABA/LAMA

ACTIVE COMPARATOR

Participants will inhale a LABA (vilanterol (25mcg)) + LAMA (umeclidinium (62.5mcg)) medication once daily for 28+ days before sitting in a booth and being exposed to diesel exhaust (standardized to 300µg/m³ of particulate matter with a diameter of 2.5 micrometers or less (PM2.5)) for 2 hours.

Drug: LABA+LAMA; Other: Diesel Exhaust

Diesel Exhaust with LABA/LAMA + ICS

EXPERIMENTAL

Participants will inhale a LABA (vilanterol (25mcg)) + LAMA (umeclidinium (62.5mcg))+ Inhaled Corticosteroid (ICS; fluticasone furoate (100mcg)) medication once daily for 28+ days before sitting in a booth and being exposed to diesel exhaust (300ug/m3 of PM2.5) for 2 hours.

Drug: LABA+LAMA+ICS; Other: Diesel Exhaust

Interventions

LABA+LAMA DRUG

1 dose per day (AM)

Also known as: Anoro Ellipta

Diesel Exhaust with LABA/LAMA; Filtered Air with LABA/LAMA

LABA+LAMA+ICS DRUG

1 dose per day (AM)

Also known as: Trelegy Ellipta

Diesel Exhaust with LABA/LAMA + ICS; Filtered Air with LABA/LAMA + ICS

Filtered Air OTHER

Exposure to HEPA filtered air, as a control

Filtered Air with LABA/LAMA; Filtered Air with LABA/LAMA + ICS

Diesel Exhaust OTHER

Diesel exhaust standardized to 300µg/m³ of particulate matter with a diameter of 2.5 micrometers or less (PM2.5).

Also known as: Traffic Related Air Pollution

Diesel Exhaust with LABA/LAMA; Diesel Exhaust with LABA/LAMA + ICS

Eligibility Criteria

• Age: 40 Years - 80 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Between the ages of 40 to 80
• Mild-to-moderate COPD diagnosis (Global Initiative for Chronic Obstructive Lung Disease stage 1-2) as confirmed by medical history, questionnaires, and spirometry (a test that measures the amount of air one can breathe in and out of the lungs) results
• Spirometry results will be assessed by the study physician to determine eligibility

You may not qualify if:

• Currently smoking or have been smoking within six months of your screening visit for this study
• Have had an acute exacerbation of COPD (AECOPD) diagnosis within 365 days of the screening visit
• Have a history of asthma or asthma-COPD overlap syndrome
• Existing medical condition or other health concerns as assessed by the study physician

Sponsors & Collaborators

• University of British Columbia: lead
• University of Calgary: collaborator
• University of Ottawa: collaborator
• University of Manitoba: collaborator
• University of North Carolina, Chapel Hill: collaborator

MeSH Terms

Conditions

Pulmonary Disease, Chronic Obstructive

Interventions

Vehicle Emissions

Condition Hierarchy (Ancestors)

Lung Diseases, Obstructive; Lung Diseases; Respiratory Tract Diseases; Chronic Disease; Disease Attributes; Pathologic Processes; Pathological Conditions, Signs and Symptoms

Intervention Hierarchy (Ancestors)

Complex Mixtures

Study Officials

• Christopher Carlsten, MD, MPH

  University of British Columbia

  PRINCIPAL INVESTIGATOR

• Neeloffer Mookherjee, PhD

  University of Manitoba

  PRINCIPAL INVESTIGATOR

• Shawn Aaron, MD, FRCPC

  University of Ottawa/Université d'Ottawa

  PRINCIPAL INVESTIGATOR

• Janice Leung, MD, FRCPC

  University of British Columbia

  PRINCIPAL INVESTIGATOR

• Christopher F Rider, PhD

  University of British Columbia

  PRINCIPAL INVESTIGATOR

• Neil Alexis, PhD

  University of North Carolina, Chapel Hill

  PRINCIPAL INVESTIGATOR

Central Study Contacts

PJ (Parteek) Johal, BCS

CONTACT

604-875-5132; p.johal@ubc.ca

Agnes Yuen, BSc

CONTACT

604-875-4111; agnes.yuen@ubc.ca

Study Design

• Study Type: interventional
• Phase: phase 4
• Allocation: RANDOMIZED
• Masking: TRIPLE
• Who Masked: PARTICIPANT, INVESTIGATOR, OUTCOMES ASSESSOR
• Masking Details: Blinding of exposures will be performed by the air pollution exposure laboratory (APEL) engineer. Visually indistinguishable inhalers will be coded by research pharmacy staff. All assays will be performed by personnel who do not know the exposure conditions of individual samples.
• Purpose: PREVENTION
• Intervention Model: CROSSOVER
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Professor

Model Details: Participants will become their own control as they experience all four combinations of exposures at four different time intervals, each separated by at least a month for washout: 1) Filtered Air-Inhaled Corticosteroid (FA-ICS), 2) Filtered Air- No Inhaled Corticosteroid (FA-no ICS), 3) Diesel Exhaust-Inhaled Corticosteroid (DE-ICS), and 4) Diesel Exhaust- No Inhaled Corticosteroid (DE-no ICS).

Study Record Dates

• First Submitted: March 28, 2024
• First Posted: August 14, 2024
• Study Start: April 1, 2025
• Primary Completion (Estimated): December 31, 2026
• Study Completion (Estimated): December 31, 2028
• Last Updated: March 27, 2025

Record last verified: 2025-03