Epigenetic Effects of Intranasal SteroidsPhase 4Project AceNCT04342039
Epigenetic Health Benefits of Budesonide
A Phase 4 study testing Budesonide Nasal in people with Epigenetic Effects of Intranasal Steroids and Environmental Exposure, run by University of British Columbia at 1 site in Canada.
Trial summary
Around 40% of the world's population is now impacted by allergic disease and this figure continues to rise. It is now understood that allergic disease arises from complex interactions between genetic and environmental factors. Read more about this study
- Who is it for?
- Ages 18 to 65 years
- Conditions the study is for
- Epigenetic Effects of Intranasal Steroids, Environmental Exposure
- What is being tested?
- Budesonide Nasal
- Could I receive a placebo?
- Yes, some participants may receive a placebo
- How many people
- 20 participants
- Where
- 1 siteCanada
- Study dates
- 7 Jan 2021to 31 Dec 2027
- Phase
- Phase 4
- Are there results?
- Not yet: the study is under way
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 18 to 65 years
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- Healthy men and women aged 18 - 65 years. (Female subjects must be postmenopausal, surgically sterile or using medically accepted contraceptive means, as judged by the investigator).
- Asymptomatic subjects (not experiencing rhinitis symptoms at the time of screening).
- A clinical diagnosis of allergic rhinitis (dust mite, grass mix or tree mix) for at least the previous two years.
- Subjects with a need of treatment for their nasal symptoms during the pollen season of such severity that it required pharmacological therapy each year for the last two consecutive years.
- Willingness to participate as indicated by a signed informed consent. Signed consent must be obtained from the subject prior to start of any study-related procedures.
- Availability and ability for all planned site visits
- A nasal allergen challenge resulting in at least five sneezes and/or a recorded score of >2 in either nasal obstruction or runny nose
Who cannot join
- Subjects with confirmed hypersensitivity to budesonide.
- Subjects with previous or current respiratory- cardiovascular-, renal-, liver-, endocrinological or other diseases or conditions which may influence the subject's participation in the study or the result hereof, as judged by the investigator.
- Subjects with a planned hospitalization or planned blood-donation during the study.
- Women who are pregnant or nursing.
- Diseases or conditions which might interfere with the evaluation of efficacy and safety:
- Subjects with structural abnormalities of the nose (e.g. septal deviation, nasal polyps) or other diseases (infectious rhinitis, sinusitis, rhinitis medicamentosa and atrophic or non- allergic rhinitis) which could cause significant nasal obstruction or other symptoms which could have any significant influence on the investigated disease as judged by the investigator.
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- History of asthma.
- PAR (with an exception, see inclusion criterion 3).
- Subjects allergic to other allergens occurring during the study period.
- Systemic corticosteroid use within 2 months, topical corticosteroid use within 2 weeks, antihistamine use within 1 week, leukotriene antagonist use within one week or immunotherapy within 2 years of baseline visit (or stop at screening)
- Upper respiratory infection within 2 weeks of baseline visit
- Use of tobacco within 1 year of baseline
- Chronic medical condition that could interfere with evaluation of rhinitis endpoints (e.g. allergic skin conditions, active infections, asthma, etc.)
Trial locations and contacts
1 site in 1 country.
Canada1 site
University of British Columbia
Vancouver, British Columbia, V5Z 1M9
About this study
Around 40% of the world's population is now impacted by allergic disease and this figure continues to rise. It is now understood that allergic disease arises from complex interactions between genetic and environmental factors. Exposure to allergens such as dust mites and pollen, as well as air pollutants such as diesel exhaust particulates, can alter the ability of critical genes to be expressed appropriately, a process known as epigenetic modification. The epigenetic modifications induced by allergens and pollutants appears to be reversible, thus providing a mechanism by which allergic disease can be treated. Budesonide (Rhinocort®) is a corticosteroid nasal spray commonly used to treat allergy symptoms. While the anti- inflammatory and other pharmacological aspects of budesonide are well understood, recent studies have suggested that budesonide may also work by reversing the epigenetic modifications caused by allergen exposure, although this has not been examined in the context of real-world exposures in humans.
This study aims to harness the power of epigenetic analysis to determine whether the epigenetic landscape in patients suffering from allergic disease can be modified by the administration of budesonide. It will fill critical gaps in understanding of epigenetic effects and provide information to examine the connection between environmental impacts and treatment effects. The research will expand the mechanistic understanding of the therapeutic effects of budesonide for relief of nasal rhinitis symptoms and may reveal new mechanisms that could improve treatment of allergies or pollution exposure, or serve as a tool for evaluating future therapies. If this venture is successful, it will serve as a model for studying and optimizing the epigenetic effects of other treatments and other diseases.
Read the detailed description
To test this, the investigators have planned for two treatment trials where participants will act as both the control and tester (crossover design method). Participants will be provided a randomized treatment order of either 1) Budesonide (Rhinocort) or 2) placebo (no medication) nasal spray for the treatment trial. Participants will go through a series of nasal sampling, symptoms questionnaires, nasal inhalation flow readings during the in-person visits at the hospital. Investigators will also attempt to mimic allergen and pollution exposures, and track how the treatment affects one's nasal responses during visits. On days where participants do not have in-person visits, participants will continue using the treatment product on a daily basis. After one cycle of treatment, participants will go through a wash-out period before starting the second cycle with the opposite treatment (Budesonide (Rhinocort)/placebo).
Investigators are not expecting that participants' responses to the treatments or exposures will be noticeable to the participants. Any responses that may occur will probably only be detectable through careful examination of the collected nasal samples on a genetic basis. However, being able to understand the subtle changes will help investigators optimize and better understand the use of these treatments in the future.
- Being tested
- Budesonide Nasal, Placebo
- Keywords
- Controlled Human Exposure Study, Budesonide Nasal Spray, Epigenetics, Gene Expression, Allergic Rhinitis
- Medical subject headings
- Rhinitis, Allergic
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Budesonide NasalDrug
Also called Rhinocort
budesonide 64 mcg/spray; 2 sprays each nostril once daily on days as indicated in the timeline
PlaceboOther
2 sprays each nostril daily on days as indicated in the timeline
| Study group | Role | What they receive |
|---|---|---|
| Placebo | Placebo comparator | Participants will use a placebo nasal spray before being exposed to a series of allergen and pollution challenges. Receives: Other: Placebo |
| Budesonide nasal | Active comparator | Participants will use budesonide nasal spray before being exposed to a series of allergen and pollution challenges. Receives: Drug: Budesonide Nasal |
What is being measured
The primary outcome is the main question the study is designed to answer.
Budesonide affect on allergic rhinitis plus allergen (48 hrs)
Change in DNA methylation in the budesonide group compared with placebo.
DNA methylation measurement tool:
Illumina Infinium MethylationEPIC BeadChip (interrogates 866,895 CpG sites across the human genome)
Unit of Measure:
For each targeted CpG site, the intensity of fluorescence will be translated into a level of DNA methylation which is either represented as a β value, a number between 0 and 1 (0 = no methylated, 1 = fully methylated) for visualization and interpretation, or a logit-transformed β value "M value" for statistical analysis.
Measured: Baseline vs 48 hours
Secondary outcomes (6)
Budesonide affect on allergic rhinitis plus allergen (24 hrs)
Change in DNA methylation in the budesonide group compared with placebo.
DNA methylation measurement tool:
Illumina Infinium MethylationEPIC BeadChip (interrogates 866,895 CpG sites across the human genome)
Unit of Measure:
For each targeted CpG site, the intensity of fluorescence will be translated into a level of DNA methylation which is either represented as a β value, a number between 0 and 1 (0 = no methylated, 1 = fully methylated) for visualization and interpretation, or a logit-transformed β value "M value" for statistical analysis.
Measured: Baseline vs 24 hours
Budesonide affect on allergic rhinitis plus pollution (48 hrs)
Change in DNA methylation in the budesonide group compared with placebo.
DNA methylation measurement tool:
Illumina Infinium MethylationEPIC BeadChip (interrogates 866,895 CpG sites across the human genome)
Unit of Measure:
For each targeted CpG site, the intensity of fluorescence will be translated into a level of DNA methylation which is either represented as a β value, a number between 0 and 1 (0 = no methylated, 1 = fully methylated) for visualization and interpretation, or a logit-transformed β value "M value" for statistical analysis.
Measured: Baseline vs 48 hours
Budesonide affect on allergic rhinitis plus pollution (24 hrs)
Change in DNA methylation in the budesonide group compared with placebo.
DNA methylation measurement tool:
Illumina Infinium MethylationEPIC BeadChip (interrogates 866,895 CpG sites across the human genome)
Unit of Measure:
For each targeted CpG site, the intensity of fluorescence will be translated into a level of DNA methylation which is either represented as a β value, a number between 0 and 1 (0 = no methylated, 1 = fully methylated) for visualization and interpretation, or a logit-transformed β value "M value" for statistical analysis.
Measured: Baseline vs 24 hours
Change in Total Nasal Symptoms Score (TNSS) (30 min)
Change from allergen baseline in Total Nasal Symptoms Score (TNSS) in the budesonide group compared with placebo 30 minutes after first allergen challenge. TNSS is evaluated on a scale of 0 to 12; with 0 being none and 12 being severe.
Measured: Baseline vs 30-minute post allergen challenge
Change in Peak Nasal Inspiratory Flow (PNIF) (30 min)
Change from allergen baseline in PNIF in the budesonide group compared with placebo 30 minutes after first allergen challenge.
Measured: Baseline vs 30-minute post allergen challenge
Changes in Concentration of Cytokines
Change in concentration of cytokines and related protein markers (such as human IL-1 beta, IL-4, IL-6, IL-10, IL-13, TNF-alpha, etc.) across groups and times in the study.
Cytokine measurement tool:
Meso Scale Discovery Multiplex and similar ELISA assays that test for the mentioned markers.
Unit of Measure:
Concentration (picograms of analyte per ml of undiluted sample) will be calculated from standard curves provided with the assays. Concentration detection ranges between 1-10,000pg/ml. Concentration values will be used for visualization and statistical analysis.
Measured: Through study completion, approximately 4 months.
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted10 Apr 2020
- Study start7 Jan 2021
- Primary completion31 Dec 2025 (estimated)
- Study completion31 Dec 2027 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (1)Papers the sponsor has linked to this study.
- Other trials for Epigenetic Effects of Intranasal SteroidsStudies 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
- Basic science
- Allocation
- Randomised
- Intervention model
- Crossover
- Model description
- Participants will visit our lab for 2 trial cycles (each cycle involves one arm): 1\) Budesonide, and 2) placebo. Within each cycle, there are periods with and without pollution exposure, so there is a secondary comparison of pre- versus post-pollution exposure.
- Masking
- Triple blind
- Who is masked
- Participant, Investigator, Outcomes assessor
- Enrolment
- 20 participants (estimated)
Sponsor and investigators
- Lead sponsor
- University of British Columbia
- Sponsor type
- University, hospital or other
- Collaborators
- Genome British Columbia, Johnson & Johnson Consumer Inc. (J&JCI)
- Responsible party
- Principal investigator, Christopher Carlsten, University of British Columbia
- Investigators
- Christopher Carlsten, MD, Principal investigator, University of British Columbia
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT04342039
- Sponsor's protocol ID
- H20-00414
- Acronym
- Project Ace
- Status last verified
- Mar 2025
- First submitted
- 9 Mar 2020
- Last updated
- 27 Mar 2025
- Results posted
- No
- Data monitoring committee
- No
- FDA-regulated drug
- No
- FDA-regulated device
- No
- Individual data sharing
- No
Publications
Halbe E, Rider CF, Yuen ACY, Johal P, Hashimoto A, MacIsaac JL, Dever K, Schwartz C, Lau KSK, Lim EL, Afshar T, Jude MS, Konwar C, Kobor MS, Carlsten C. Nasal budesonide mitigates air pollution effects in adults with allergic rhinitis: A randomized trial. Ann Allergy Asthma Immunol. 2026 Aug;137(2):216-224.e19. doi: 10.1016/j.anai.2026.02.004. Epub 2026 Feb 25.
PubMed 41759721
Study at a glance
From the registry record, last updated by the sponsor on 27 Mar 2025. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Epigenetic Health Benefits of Budesonide
- ClinicalTrials.gov ID
- NCT04342039
- Acronym / sponsor ID
- Project Ace / H20-00414
- Keywords
- Controlled Human Exposure Study, Budesonide Nasal Spray, Epigenetics, Gene Expression, Allergic Rhinitis
- Phase
- Phase 4
- Study type
- Interventional
- Recruitment status
- Active, not recruiting
- Enrolment
- 20 participants (estimated)
- Lead sponsor
- University of British ColumbiaUniversity, hospital or other
- Collaborators
- Genome British Columbia, Johnson & Johnson Consumer Inc. (J&JCI)
- Study start
- 7 Jan 2021 (actual)
- Primary completion
- 31 Dec 2025 (estimated)
- Study completion
- 31 Dec 2027 (estimated)
- First posted
- 10 Apr 2020 (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.
Around 40% of the world's population is now impacted by allergic disease and this figure continues to rise. It is now understood that allergic disease arises from complex interactions between genetic and environmental factors. Exposure to allergens such as dust mites and pollen, as well as air pollutants such as diesel exhaust particulates, can alter the ability of critical genes to be expressed appropriately, a process known as epigenetic modification. The epigenetic modifications induced by allergens and pollutants appears to be reversible, thus providing a mechanism by which allergic disease can be treated. Budesonide (Rhinocort®) is a corticosteroid nasal spray commonly used to treat allergy symptoms. While the anti- inflammatory and other pharmacological aspects of budesonide are well understood, recent studies have suggested that budesonide may also work by reversing the epigenetic modifications caused by allergen exposure, although this has not been examined in the context of real-world exposures in humans.
This study aims to harness the power of epigenetic analysis to determine whether the epigenetic landscape in patients suffering from allergic disease can be modified by the administration of budesonide. It will fill critical gaps in understanding of epigenetic effects and provide information to examine the connection between environmental impacts and treatment effects. The research will expand the mechanistic understanding of the therapeutic effects of budesonide for relief of nasal rhinitis symptoms and may reveal new mechanisms that could improve treatment of allergies or pollution exposure, or serve as a tool for evaluating future therapies. If this venture is successful, it will serve as a model for studying and optimizing the epigenetic effects of other treatments and other diseases.
Detailed description
To test this, the investigators have planned for two treatment trials where participants will act as both the control and tester (crossover design method). Participants will be provided a randomized treatment order of either 1) Budesonide (Rhinocort) or 2) placebo (no medication) nasal spray for the treatment trial. Participants will go through a series of nasal sampling, symptoms questionnaires, nasal inhalation flow readings during the in-person visits at the hospital. Investigators will also attempt to mimic allergen and pollution exposures, and track how the treatment affects one's nasal responses during visits. On days where participants do not have in-person visits, participants will continue using the treatment product on a daily basis. After one cycle of treatment, participants will go through a wash-out period before starting the second cycle with the opposite treatment (Budesonide (Rhinocort)/placebo).
Investigators are not expecting that participants' responses to the treatments or exposures will be noticeable to the participants. Any responses that may occur will probably only be detectable through careful examination of the collected nasal samples on a genetic basis. However, being able to understand the subtle changes will help investigators optimize and better understand the use of these treatments in the future.
Study design
- Primary purpose
- Basic science
- Allocation
- Randomised
- Intervention model
- Crossover
- Masking
- Triple blind (participant, investigator, outcomes assessor)
- Number of arms
- 2
- Model description
- Participants will visit our lab for 2 trial cycles (each cycle involves one arm): 1) Budesonide, and 2) placebo. Within each cycle, there are periods with and without pollution exposure, so there is a secondary comparison of pre- versus post-pollution exposure.
| Arm | Type | Receives |
|---|---|---|
| Placebo | Placebo comparator | Other: PlaceboParticipants will use a placebo nasal spray before being exposed to a series of allergen and pollution challenges. |
| Budesonide nasal | Active comparator | Drug: Budesonide NasalParticipants will use budesonide nasal spray before being exposed to a series of allergen and pollution challenges. |
Who may qualify
- Ages
- 18 to 65 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (7 listed)
- Healthy men and women aged 18 - 65 years. (Female subjects must be postmenopausal, surgically sterile or using medically accepted contraceptive means, as judged by the investigator).
- Asymptomatic subjects (not experiencing rhinitis symptoms at the time of screening).
- A clinical diagnosis of allergic rhinitis (dust mite, grass mix or tree mix) for at least the previous two years.
- Subjects with a need of treatment for their nasal symptoms during the pollen season of such severity that it required pharmacological therapy each year for the last two consecutive years.
- Willingness to participate as indicated by a signed informed consent. Signed consent must be obtained from the subject prior to start of any study-related procedures.
Key exclusion criteria (13 listed)
- Subjects with confirmed hypersensitivity to budesonide.
- Subjects with previous or current respiratory- cardiovascular-, renal-, liver-, endocrinological or other diseases or conditions which may influence the subject's participation in the study or the result hereof, as judged by the investigator.
- Subjects with a planned hospitalization or planned blood-donation during the study.
- Women who are pregnant or nursing.
- Diseases or conditions which might interfere with the evaluation of efficacy and safety:
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 |
|---|---|---|
| Budesonide NasalAlso: Rhinocortbudesonide 64 mcg/spray; 2 sprays each nostril once daily on days as indicated in the timeline | Drug | Budesonide nasal |
| Placebo2 sprays each nostril daily on days as indicated in the timeline | Other | Placebo |
Primary outcome
Budesonide affect on allergic rhinitis plus allergen (48 hrs)
Time frame: Baseline vs 48 hours
Change in DNA methylation in the budesonide group compared with placebo. DNA methylation measurement tool: Illumina Infinium MethylationEPIC BeadChip (interrogates 866,895 CpG sites across the human genome) Unit of Measure: For each targeted CpG site, the intensity of fluorescence will be translated into a level of DNA methylation which is either represented as a β value, a number between 0 and 1 (0 = no methylated, 1 = fully methylated) for visualization and interpretation, or a logit-transformed β value "M value" for statistical analysis.
6 secondary outcomes
Budesonide affect on allergic rhinitis plus allergen (24 hrs)
Time frame: Baseline vs 24 hours
Budesonide affect on allergic rhinitis plus pollution (48 hrs)
Time frame: Baseline vs 48 hours
Budesonide affect on allergic rhinitis plus pollution (24 hrs)
Time frame: Baseline vs 24 hours
Change in Total Nasal Symptoms Score (TNSS) (30 min)
Time frame: Baseline vs 30-minute post allergen challenge
Change in Peak Nasal Inspiratory Flow (PNIF) (30 min)
Time frame: Baseline vs 30-minute post allergen challenge
Changes in Concentration of Cytokines
Time frame: Through study completion, approximately 4 months.
Results and safety
This study is still under way. Results are not available in the source record yet.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 27 Mar 2025.
- Derived from this study: PubMed 41759721Halbe E, Rider CF, Yuen ACY, Johal P, Hashimoto A, MacIsaac JL, Dever K, Schwartz C, Lau KSK, Lim EL, Afshar T, Jude MS, Konwar C, Kobor MS, Carlsten C. Nasal budesonide mitigates air pollution effects in adults with allergic rhinitis: A randomized trial. Ann Allergy Asthma Immunol. 2026 Aug;137(2):216-224.e19. doi: 10.1016/j.anai.2026.02.004. Epub 2026 Feb 25.
- Individual participant dataSharing planned: No
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.
Christopher Carlsten, MD principal investigator
University of British Columbia
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 Nasal in people with Epigenetic Effects of Intranasal Steroids and Environmental Exposure, 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 7 inclusion and 13 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: under way, not looking for participants, as of the sponsor's last update on 27 Mar 2025. 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?
This study is still under way. Results are not available in the source record yet.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Budesonide affect on allergic rhinitis plus allergen (48 hrs) (time frame: Baseline vs 48 hours). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT04342039, which also lists 1 linked publication.
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 27 Mar 2025.