Clinical trial NCT06552364: Air Pollution and Inhaled Corticosteroids in COPD
Official title: Air Pollution and Inhaled Corticosteroids in COPD
Study type: INTERVENTIONAL
Overall status: NOT_YET_RECRUITING
Phase: PHASE4
Conditions: COPD
Keywords: Air Pollution
Inhaled Corticosteroid
LABA/LAMA
Triple Therapy (LABA/LAMA/ICS)
Lead sponsor: University of British Columbia
Sponsor class: OTHER
Collaborators: name: University of Calgary
name: University of Ottawa
name: University of Manitoba
name: University of North Carolina, Chapel Hill
First posted: 2024-08-14
Enrollment: 48
Sex: ALL
Minimum age (years): 40
Maximum age (years): 80
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: CROSSOVER
Intervention model description: 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).
Primary purpose: PREVENTION

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.

Detailed description: APIC will involve 48 volunteer participants (24 of each biological sex assigned at birth) with mild-to-moderate COPD where the researchers will look at what (if any) are the differences between breathing in fresh air (filtered air - FA) or polluted air (diesel exhaust - DE) while taking the drug (Inhaled corticosteroid - ICS) or not (no ICS), both in combination with two standard COPD medicines that make it easier to breath (a long-acting beta-agonist and a long-acting muscarinic antagonist). The participant will take an inhaled medication daily throughout the study. This study will use a controlled amount of diesel exhaust to model traffic-related air pollution (TRAP), a commonly encountered form of polluted air.

Each participant will act as their own control, as they will experience all four combinations: 1) FA-ICS, 2) FA-no ICS, 3) DE-ICS, and 4) DE-no ICS. These combinations will be randomized in what researchers call a double-blinded crossover study, so that every participant will get these combinations in a different order. However, only the engineer on the team will be allowed to know which participant gets what. Blinding will prevent everyone else, including the participant, from being biased against the conditions and affecting outcomes based on this perception.

The study will span over five months (approximately 121 days of active commitment), which includes ten in-person visits to a research office at the Vancouver General Hospital, for a total of approximately 40 hours. While the participant is on-site, the investigators will supervise a series of questionnaires, sample collection (blood, urine, bronchoscopy lung samples), and lung function tests. The investigators will evaluate multiple endpoints as detailed in the Outcome Measures section. For each applicable endpoint, the investigators will evaluate stratified analyses and effect modification by biological sex, participant age, gene score, and microbiomes.

The investigators do not expect that the participant's responses to either the corticosteroid or diesel exhaust will be noticeable to them. Any responses that may occur will probably only be detectable through careful examination of their cells and tissues (e.g., blood, urine, bronchial samples). However, understanding the subtle changes that may occur could help reduce or prevent health problems associated with TRAP exposure in the future.

Eligibility criteria: Inclusion Criteria:

* 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

Exclusion Criteria:

* 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
* Pregnant, plan to be pregnant, or breastfeeding during your enrolment in the study. Participants of childbearing potential will be required to have a negative pregnancy test prior to study inclusion.

Primary outcomes:
measure: Inhaled corticosteroid (ICS) and/or diesel exhaust exposure effects on inflammatory cells.
timeFrame: Comparison of the different arms over the span of 5 months.
measure: Inhaled corticosteroid (ICS) and/or diesel exhaust exposure effects on exhaled nitric oxide.
timeFrame: Comparison of the different arms over the span of 5 months.
measure: Inhaled corticosteroid (ICS) and/or diesel exhaust exposure effects on anti-microbial host defense proteins.
timeFrame: Comparison of the different arms over the span of 5 months.
measure: Inhaled corticosteroid (ICS) and/or diesel exhaust exposure effects on oxidative stress in the lungs.
timeFrame: Comparison of the different arms over the span of 5 months.
measure: Inhaled corticosteroid (ICS) and/or diesel exhaust exposure effects on neutrophil extracellular TRAPs (NETs).
timeFrame: Comparison of the different arms over the span of 5 months.
measure: Inhaled corticosteroid (ICS) and/or diesel exhaust exposure effects on lung inflammatory markers.
timeFrame: Comparison of the different arms over the span of 5 months.
Secondary outcomes:
measure: Inhaled corticosteroids (ICS) and/or diesel exhaust exposure induced modulation of circulating markers of inflammation.
timeFrame: Comparison of the different arms over the span of 5 months.
measure: Inhaled corticosteroid (ICS) and/or diesel exhaust exposure induced modulation of circulating cells and inflammatory cellular markers.
timeFrame: Comparison of the different arms over the span of 5 months.
measure: Inhaled corticosteroid (ICS) and/or diesel exhaust exposure induced modulation of lung resistance as assessed by oscillometry.
timeFrame: Comparison of the different arms over the span of 5 months.
measure: Inhaled corticosteroid (ICS) and/or diesel exhaust exposure effects on lung function.
timeFrame: Comparison of the different arms over the span of 5 months.
measure: Effects of inhaled corticosteroids (ICS) and/or diesel exhaust on neutrophil function.
timeFrame: Comparison of the different arms over the span of 5 months.
measure: Effects of inhaled corticosteroids (ICS) and/or diesel exhaust on phagocytosis.
timeFrame: Comparison of the different arms over the span of 5 months.
measure: Effects of inhaled corticosteroids (ICS) and/or diesel exhaust on the EXACT (and E-RS:COPD) questionnaire.
timeFrame: Comparison of the different arms over the span of 5 months.
measure: Effects of inhaled corticosteroids (ICS) and/or diesel exhaust on the mMRC dyspnea scale questionnaire.
timeFrame: Comparison of the different arms over the span of 5 months.
measure: Effects of inhaled corticosteroids (ICS) and/or diesel exhaust on the Symptoms and Perception questionnaire.
timeFrame: Comparison of the different arms over the span of 5 months.
measure: Effects of inhaled corticosteroids (ICS) and/or diesel exhaust on the Perceived Stress Scale questionnaire.
timeFrame: Comparison of the different arms over the span of 5 months.
Other outcomes:
Locations:
Study officials:
affiliation: University of British Columbia
name: Christopher Carlsten, MD, MPH
role: PRINCIPAL_INVESTIGATOR
affiliation: University of Manitoba
name: Neeloffer Mookherjee, PhD
role: PRINCIPAL_INVESTIGATOR
affiliation: University of Ottawa/Université d'Ottawa
name: Shawn Aaron, MD, FRCPC
role: PRINCIPAL_INVESTIGATOR
affiliation: University of British Columbia
name: Janice Leung, MD, FRCPC
role: PRINCIPAL_INVESTIGATOR
affiliation: University of British Columbia
name: Christopher F Rider, PhD
role: PRINCIPAL_INVESTIGATOR
affiliation: University of North Carolina, Chapel Hill
name: Neil Alexis, PhD
role: PRINCIPAL_INVESTIGATOR
References: