Exposure to PollutionPhase 4DIGRNCT03615742
Diesel Exhaust Induces Glucocorticoid Resistance
A Phase 4 study testing Budesonide, Filtered Air and Diesel Exhaust in people with Exposure to Pollution and Glucocorticoid Resistance, run by University of British Columbia at 1 site in Canada.
Trial 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… Read more about this study
- Who is it for?
- Ages 19 to 49 years
- Conditions the study is for
- Exposure to Pollution, Glucocorticoid Resistance
- What is being tested?
- Budesonide, Filtered Air and Diesel Exhaust
- Could I receive a placebo?
- Yes, some participants may receive a placebo
- How many people
- 30 participants
- Where
- 1 siteCanada
- Study dates
- 1 Dec 2018to 31 Dec 2025
- Phase
- Phase 4
- Are there results?
- None posted in the registry
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 19 to 49 years
- All sexes
- No healthy volunteers
- Adult
Who may be able to join
- 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
Who cannot join
- 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
Show all 10Show fewer
- 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
Trial locations and contacts
1 site in 1 country.
Canada1 site, 1 recruiting
- Recruiting
University of British Columbia
Vancouver, British Columbia, V5Z1M9
Chris Carlsten, MD MPH, 604-875-4729, carlsten@mail.ubc.ca
Ryan D Huff, MSc, 604-875-5132, digr.study@ubc.ca
About this study
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.
Read the detailed description
- Purpose Inhalation of air pollutants leads to both airway inflammation, with increased cytokine expression and inflammatory cell recruitment to the airways, and to airway hyperresponsiveness, which together contribute to airway resistance and breathing difficulties. Correlational data indicate that exposure to air pollution increases inhaled corticosteroids (ICS) use in asthmatics, suggesting that steroidal anti-inflammatory medications are suboptimally effective under these conditions. However, a major issue is that no study has yet been performed specifically to determine the effects of controlled diesel exhaust (DE) exposure on responses to ICS. Furthermore, investigators need better insight into mechanisms, including the effects of epigenetic modifications and polymorphisms in oxidative stress response genes, which remain under explored. Investigators anticipate that an improved understanding of air pollution-induced ICS hyporesponsiveness (reduced effectiveness) could underpin preventative guidelines, guide ICS usage in response to environmental exposures, and inform rational pharmaceutical development. Ultimately this could lead to fewer exacerbations in asthmatic and other susceptible populations.
Hypothesis:
Acute exposure to DE reduces ICS-inducible gene expression in vivo in asthmatics, in part through effects on epigenetic processes.
Justification:
Air pollution exposure correlates with increased use of ICS inhalers in asthmatics, suggesting that ICS offer less control during periods of higher air pollution. As genes induced by ICS are critical in reducing inflammatory messenger ribonucleic acid (mRNA) and protein expression, the investigators have chosen to focus on the effects of DE on ICS-inducible gene expression as our primary endpoint.
Research Method:
To test this the effects of air pollution exposure on a corticosteroid, volunteers will inhale either a placebo (inhaler containing no medication) or budesonide (1.6mg), before sitting in our exposure booth for 2 hours breathing either filtered air (as a control) or diluted diesel exhaust (standardized to 300µg/m³ of particulate matter with a diameter of 2.5 micrometers or less).
Volunteers will visit our lab four different times to be exposed to: 1) placebo \& filtered air, 2) placebo \& diesel exhaust, 3) corticosteroid and filtered air, and 4) corticosteroid and diesel exhaust. Investigators can then compare responses to each of these combinations of exposures.
Investigators will take blood samples before and after volunteers complete each of these exposures to track how they affect the body. Six hours after placebo or budesonide inhalation a research bronchoscopy will be performed during which a very thin flexible tube will be inserted through the mouth and down into lungs to collect samples from each volunteer.
Bronchoalveolar lavage, bronchial washes, bronchial brushes and tissue biopsies will be obtained for analysis of gene expression and epigenetic endpoints. Nasal lavage samples will also be collected to examine responses in the upper airways and blood and urine will be studied to examine systemic responses. Spirometry will be used to assess effects on airway function.
- Conditions
- Exposure to Pollution, Glucocorticoid Resistance
- Being tested
- Placebo, Budesonide, Filtered Air, Diesel Exhaust
- Keywords
- Diesel Exhaust, Air Pollution, Inhaled Corticosteroids, Gene Expression, Asthma, Controlled Human Exposure Study
- Medical subject headings
- Glucocorticoid Receptor Deficiency, Asthma
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
PlaceboOther
Inhalation of air through a Turbuhaler that contains no medication, as a control.
BudesonideDrug
Also called Pulmicort
1.6mg of budesonide from a Turbuhaler.
Filtered AirOther
Exposure to HEPA filtered air, as a control.
Diesel ExhaustOther
Also called Traffic Related Air Pollution
Diesel exhaust standardized to 300µg/m³ of particulate matter with a diameter of 2.5 micrometers or less (PM2.5).
| Study group | Role | What they receive |
|---|---|---|
| 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. Receives: 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. Receives: 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. Receives: 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. Receives: Drug: Budesonide; Other: Diesel Exhaust |
What is being measured
The primary outcome is the main question the study is designed to answer.
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)
Measured: Baseline versus 6 hours
Secondary outcomes (1)
Modification by variants in genes governing inflammation and responses to oxidative stress after DE exposure and ICS.
Genotypes will be assessed using Applied Biosystems Axiom Precision Medicine Research arrays, with validation by polymerase chain reaction assay (PCR). The data generated will be used to generate a gene score (single value for each participant) which will be used for statistical interaction analysis.
Measured: Baseline versus 6 hours
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted6 Aug 2018
- Study start1 Dec 2018
- Primary completion31 Dec 2025 (estimated)
- Study completion31 Dec 2025 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Exposure to PollutionStudies of the same condition, open and under way.
- More trials run by University of British ColumbiaThe sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 4
- Primary purpose
- Prevention
- Allocation
- Randomised
- Intervention model
- Crossover
- Model description
- 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
- Masking
- Triple blind
- Who is masked
- Participant, Investigator, Outcomes assessor
- Enrolment
- 30 participants (estimated)
Sponsor and investigators
- Lead sponsor
- University of British Columbia
- Sponsor type
- University, hospital or other
- Collaborators
- Canadian Institutes of Health Research (CIHR), AllerGen NCE Inc.
- Responsible party
- Principal investigator, Christopher Carlsten, University of British Columbia
- Investigators
- Chris Carlsten, MD, Principal investigator, University of British ColumbiaChristopher F Rider, PhD, Study director, University of British ColumbiaRobert Newton, PhD, Study director, University of Calgary
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT03615742
- Sponsor's protocol ID
- H17-01336
- Acronym
- DIGR
- Status last verified
- Jul 2024
- First submitted
- 23 Jul 2018
- Last updated
- 24 Jul 2024
- Results posted
- No
- Data monitoring committee
- No
- FDA-regulated drug
- No
- FDA-regulated device
- No
- Individual data sharing
- No
Study at a glance
From the registry record, last updated by the sponsor on 24 Jul 2024. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Diesel Exhaust Induces Glucocorticoid Resistance
- ClinicalTrials.gov ID
- NCT03615742
- Acronym / sponsor ID
- DIGR / H17-01336
- Conditions
- Exposure to Pollution, Glucocorticoid Resistance
- Keywords
- Diesel Exhaust, Air Pollution, Inhaled Corticosteroids, Gene Expression, Asthma, Controlled Human Exposure Study
- Phase
- Phase 4
- Study type
- Interventional
- Recruitment status
- Unknown status
- Enrolment
- 30 participants (estimated)
- Lead sponsor
- University of British ColumbiaUniversity, hospital or other
- Collaborators
- Canadian Institutes of Health Research (CIHR), AllerGen NCE Inc.
- Study start
- 1 Dec 2018 (actual)
- Primary completion
- 31 Dec 2025 (estimated)
- Study completion
- 31 Dec 2025 (estimated)
- First posted
- 6 Aug 2018 (actual)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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.
Detailed description
- Purpose Inhalation of air pollutants leads to both airway inflammation, with increased cytokine expression and inflammatory cell recruitment to the airways, and to airway hyperresponsiveness, which together contribute to airway resistance and breathing difficulties. Correlational data indicate that exposure to air pollution increases inhaled corticosteroids (ICS) use in asthmatics, suggesting that steroidal anti-inflammatory medications are suboptimally effective under these conditions. However, a major issue is that no study has yet been performed specifically to determine the effects of controlled diesel exhaust (DE) exposure on responses to ICS. Furthermore, investigators need better insight into mechanisms, including the effects of epigenetic modifications and polymorphisms in oxidative stress response genes, which remain under explored. Investigators anticipate that an improved understanding of air pollution-induced ICS hyporesponsiveness (reduced effectiveness) could underpin preventative guidelines, guide ICS usage in response to environmental exposures, and inform rational pharmaceutical development. Ultimately this could lead to fewer exacerbations in asthmatic and other susceptible populations.
Hypothesis:
Acute exposure to DE reduces ICS-inducible gene expression in vivo in asthmatics, in part through effects on epigenetic processes.
Justification:
Air pollution exposure correlates with increased use of ICS inhalers in asthmatics, suggesting that ICS offer less control during periods of higher air pollution. As genes induced by ICS are critical in reducing inflammatory messenger ribonucleic acid (mRNA) and protein expression, the investigators have chosen to focus on the effects of DE on ICS-inducible gene expression as our primary endpoint.
Research Method:
To test this the effects of air pollution exposure on a corticosteroid, volunteers will inhale either a placebo (inhaler containing no medication) or budesonide (1.6mg), before sitting in our exposure booth for 2 hours breathing either filtered air (as a control) or diluted diesel exhaust (standardized to 300µg/m³ of particulate matter with a diameter of 2.5 micrometers or less).
Volunteers will visit our lab four different times to be exposed to: 1) placebo \& filtered air, 2) placebo \& diesel exhaust, 3) corticosteroid and filtered air, and 4) corticosteroid and diesel exhaust. Investigators can then compare responses to each of these combinations of exposures.
Investigators will take blood samples before and after volunteers complete each of these exposures to track how they affect the body. Six hours after placebo or budesonide inhalation a research bronchoscopy will be performed during which a very thin flexible tube will be inserted through the mouth and down into lungs to collect samples from each volunteer.
Bronchoalveolar lavage, bronchial washes, bronchial brushes and tissue biopsies will be obtained for analysis of gene expression and epigenetic endpoints. Nasal lavage samples will also be collected to examine responses in the upper airways and blood and urine will be studied to examine systemic responses. Spirometry will be used to assess effects on airway function.
Study design
- Primary purpose
- Prevention
- Allocation
- Randomised
- Intervention model
- Crossover
- Masking
- Triple blind (participant, investigator, outcomes assessor)
- Number of arms
- 4
- Model description
- 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
| Arm | Type | Receives |
|---|---|---|
| Placebo and Filtered Air | Placebo comparator | Other: Placebo, Other: Filtered AirVolunteers 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. |
| Budesonide and Filtered Air | Active comparator | Drug: Budesonide, Other: Filtered AirVolunteers will inhale 1.6mg of budesonide before sitting in a booth and being exposed to HEPA filtered air for 2 hours. |
| Placebo and Diesel Exhaust | Active comparator | Other: Placebo, Other: Diesel ExhaustVolunteers 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. |
| Budesonide and Diesel Exhaust | Experimental | Drug: Budesonide, Other: Diesel ExhaustVolunteers will inhale 1.6mg of budesonide before sitting in a booth and being exposed to 300µg/m³ concentration of diesel exhaust for 2 hours. |
Who may qualify
- Ages
- 19 to 49 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult
Key inclusion criteria (2 listed)
- 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
Key exclusion criteria (10 listed)
- 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
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| PlaceboInhalation of air through a Turbuhaler that contains no medication, as a control. | Other | Placebo and Diesel Exhaust, Placebo and Filtered Air |
| BudesonideAlso: Pulmicort1.6mg of budesonide from a Turbuhaler. | Drug | Budesonide and Diesel Exhaust, Budesonide and Filtered Air |
| Filtered AirExposure to HEPA filtered air, as a control. | Other | Budesonide and Filtered Air, Placebo and Filtered Air |
| Diesel ExhaustAlso: Traffic Related Air PollutionDiesel exhaust standardized to 300µg/m³ of particulate matter with a diameter of 2.5 micrometers or less (PM2.5). | Other | Budesonide and Diesel Exhaust, Placebo and Diesel Exhaust |
Primary outcome
Change in DNA methylation, mRNA and protein expression attributable to diesel exhaust and inhaled corticosteroid
Time frame: Baseline versus 6 hours
EPIC arrays and RNA Seq will be used to determine effect of exposure(s)
1 secondary outcome
Modification by variants in genes governing inflammation and responses to oxidative stress after DE exposure and ICS.
Time frame: Baseline versus 6 hours
Results and safety
Results are not available in the source record.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 24 Jul 2024.
- Individual participant dataSharing planned: No
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Chris Carlsten, MD principal investigator
University of British Columbia
Christopher F Rider, PhD study director
University of British Columbia
Robert Newton, PhD study director
University of Calgary
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 4 study testing Budesonide, Filtered Air and Diesel Exhaust in people with Exposure to Pollution and Glucocorticoid Resistance, run by University of British Columbia at 1 site in Canada.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 2 inclusion and 10 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: status not confirmed, as of the sponsor's last update on 24 Jul 2024. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in Canada. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. Some participants in this study may receive a placebo. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 4 studies take place after a treatment is approved, to learn more about its long-term benefits and risks in everyday use.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
Results are not available in the source record.
How can a doctor refer a patient or contact the research team?
Contact Parteek (PJ) Johal, BCS (6048755132, de.study@ubc.ca), or a site near the patient. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Change in DNA methylation, mRNA and protein expression attributable to diesel exhaust and inhaled corticosteroid (time frame: Baseline versus 6 hours). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 24 Jul 2024.