Diesel Exhaust Induces Glucocorticoid Resistance

NCT03615742 | Recruiting Phase 4

• 1 other identifier: H17-01336
• Study Type: interventional
• Target: 30
• Locations: 1 country
• Sites: 1

Brief Summary

The investigators are studying the effects of exposure to diesel exhaust on lung inflammation in the presence and absence of an inhaled corticosteroid. Although data is mixed, studies show that asthmatics have increased lung inflammation and worse symptoms during periods of higher air pollution despite taking their anti-inflammatory corticosteroid medication. One possible reason is that air pollution exposure may decrease the ability of corticosteroids to combat inflammation. To test this volunteers will inhale either a placebo or a corticosteroid, before sitting in an exposure booth for 2 hours breathing either filtered air or diluted diesel exhaust. Samples will be collected before and after exposure to analyze the effects of budesonide and diesel exhaust exposure.

Conditions

Exposure to Pollution; Glucocorticoid Resistance

Keywords

Diesel Exhaust; Air Pollution; Inhaled Corticosteroids; Gene Expression; Asthma; Controlled Human Exposure Study

Outcome Measures

Primary Outcomes (1)

• Change in DNA methylation, mRNA and protein expression attributable to diesel exhaust and inhaled corticosteroid

  EPIC arrays and RNA Seq will be used to determine effect of exposure(s)

  Baseline versus 6 hours

Secondary Outcomes (1)

• Modification by variants in genes governing inflammation and responses to oxidative stress after DE exposure and ICS.

  Baseline versus 6 hours

Study Arms (4)

Placebo and Filtered Air

PLACEBO COMPARATOR

Volunteers will use an inhaler that does not contain any medication, before sitting in a booth and being exposed to high-efficiency particulate air (HEPA) filtered air for 2 hours.

Other: Placebo; Other: Filtered Air

Budesonide and Filtered Air

ACTIVE COMPARATOR

Volunteers will inhale 1.6mg of budesonide before sitting in a booth and being exposed to HEPA filtered air for 2 hours.

Drug: Budesonide; Other: Filtered Air

Placebo and Diesel Exhaust

ACTIVE COMPARATOR

Volunteers will use an inhaler that does not contain any medication, before sitting in a booth and being exposed to 300µg/m³ concentration of diesel exhaust for 2 hours.

Other: Placebo; Other: Diesel Exhaust

Budesonide and Diesel Exhaust

EXPERIMENTAL

Volunteers will inhale 1.6mg of budesonide before sitting in a booth and being exposed to 300µg/m³ concentration of diesel exhaust for 2 hours.

Drug: Budesonide; Other: Diesel Exhaust

Interventions

Placebo OTHER

Inhalation of air through a Turbuhaler that contains no medication, as a control.

Placebo and Diesel Exhaust; Placebo and Filtered Air

Budesonide DRUG

1.6mg of budesonide from a Turbuhaler.

Also known as: Pulmicort

Budesonide and Diesel Exhaust; Budesonide and Filtered Air

Filtered Air OTHER

Exposure to HEPA filtered air, as a control.

Budesonide and Filtered Air; Placebo and Filtered Air

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

Budesonide and Diesel Exhaust; Placebo and Diesel Exhaust

Eligibility Criteria

• Age: 19 Years - 49 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64)

You may qualify if:

• Aged 19-49
• Have physician-diagnosed asthma confirmed by the study physician examination, spirometry, methacholine challenge provocative concentration causing a 20% fall (PC20) of \<16 mg/mL, and questionnaires during a screening visit

You may not qualify if:

• Smoking of any kind (0.5 pack-years ever, or any current) or use of vape/vaporizing devices
• Regular anti-histamine, NSAID, corticosteroid or other controller medication use
• Pregnancy or breastfeeding
• Methacholine PC20 \>16
• Relevant cardiac condition or arrhythmia
• Body mass index of \>35
• Currently participating in another study that may interfere with this study
• Use of either inhaled or oral corticosteroids in preceding 6 months
• Substantial comorbidities on study physician's examination or other concerns
• Surgery scheduled before anticipated study completion

Sponsors & Collaborators

• University of British Columbia: lead
• Canadian Institutes of Health Research (CIHR): collaborator
• AllerGen NCE Inc.: collaborator

Study Sites (1)

University of British Columbia

Vancouver, British Columbia, V5Z1M9, Canada

RECRUITING

MeSH Terms

Conditions

Glucocorticoid Receptor Deficiency; Asthma

Interventions

Budesonide; Vehicle Emissions

Condition Hierarchy (Ancestors)

Bronchial Diseases; Respiratory Tract Diseases; Lung Diseases, Obstructive; Lung Diseases; Respiratory Hypersensitivity; Hypersensitivity, Immediate; Hypersensitivity; Immune System Diseases

Intervention Hierarchy (Ancestors)

Pregnenediones; Pregnenes; Pregnanes; Steroids; Fused-Ring Compounds; Polycyclic Compounds; Complex Mixtures

Study Officials

• Chris Carlsten, MD

  University of British Columbia

  PRINCIPAL INVESTIGATOR

• Christopher F Rider, PhD

  University of British Columbia

  STUDY DIRECTOR

• Robert Newton, PhD

  University of Calgary

  STUDY DIRECTOR

Central Study Contacts

Parteek (PJ) Johal, BCS

CONTACT

6048755132; de.study@ubc.ca

Agnes CY Yuen, BSc

CONTACT

6048754111; 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, who will not interact with volunteers. Visually indistinguishable placebo and budesonide 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: Principal Investigator

Model Details: Volunteers will visit our lab four different times to be exposed to: 1) placebo \& filtered air, 2) placebo \& diesel exhaust, 3) budesonide and filtered air, and 4) budesonide and diesel exhaust

Study Record Dates

• First Submitted: July 23, 2018
• First Posted: August 6, 2018
• Study Start: December 1, 2018
• Primary Completion: December 31, 2025
• Study Completion: December 31, 2025
• Last Updated: July 24, 2024

Record last verified: 2024-07

Data Sharing

• IPD Sharing: Will not share

Locations

CA (1)