Epigenetic Health Benefits of Budesonide

NCT04342039 | Active Not Recruiting Phase 4

• 1 other identifier: H20-00414
• Study Type: interventional
• Target: 20
• Locations: 1 country
• Sites: 1

Brief 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. 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.

Conditions

Epigenetic Effects of Intranasal Steroids; Environmental Exposure

Keywords

Controlled Human Exposure Study; Budesonide Nasal Spray; Epigenetics; Gene Expression; Allergic Rhinitis

Outcome Measures

Primary Outcomes (1)

• 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.

  Baseline vs 48 hours

Secondary Outcomes (6)

• Budesonide affect on allergic rhinitis plus allergen (24 hrs)

  Baseline vs 24 hours

• Budesonide affect on allergic rhinitis plus pollution (48 hrs)

  Baseline vs 48 hours

• Budesonide affect on allergic rhinitis plus pollution (24 hrs)

  Baseline vs 24 hours

• Change in Total Nasal Symptoms Score (TNSS) (30 min)

  Baseline vs 30-minute post allergen challenge

• Change in Peak Nasal Inspiratory Flow (PNIF) (30 min)

  Baseline vs 30-minute post allergen challenge

Other Outcomes (5)

• Change in Total Nasal Symptoms Score (TNSS) (48 hrs)

  Baseline vs 48 hours

• Change in Total Nasal Symptoms Score (TNSS) (24 hrs)

  Baseline vs 24 hours

• Change in Peak Nasal Inspiratory Flow (PNIF) (48 hrs)

  Baseline vs 48 hours

Study Arms (2)

Placebo

PLACEBO COMPARATOR

Participants will use a placebo nasal spray before being exposed to a series of allergen and pollution challenges.

Other: Placebo

Budesonide nasal

ACTIVE COMPARATOR

Participants will use budesonide nasal spray before being exposed to a series of allergen and pollution challenges.

Drug: Budesonide Nasal

Interventions

Budesonide Nasal DRUG

budesonide 64 mcg/spray; 2 sprays each nostril once daily on days as indicated in the timeline

Also known as: Rhinocort

Budesonide nasal

Placebo OTHER

2 sprays each nostril daily on days as indicated in the timeline

Placebo

Eligibility Criteria

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

You may qualify if:

• 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

You may not qualify if:

• 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.
• History of asthma.
• 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.)

Sponsors & Collaborators

• University of British Columbia: lead
• Genome British Columbia: collaborator
• Johnson & Johnson Consumer Inc. (J&JCI): collaborator

Study Sites (1)

University of British Columbia

Vancouver, British Columbia, V5Z 1M9, Canada

Location

MeSH Terms

Conditions

Rhinitis, Allergic

Interventions

Budesonide

Condition Hierarchy (Ancestors)

Rhinitis; Nose Diseases; Respiratory Tract Diseases; Respiratory Hypersensitivity; Otorhinolaryngologic Diseases; Hypersensitivity, Immediate; Hypersensitivity; Immune System Diseases

Intervention Hierarchy (Ancestors)

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

Study Officials

• Christopher Carlsten, MD

  University of British Columbia

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 4
• Allocation: RANDOMIZED
• Masking: TRIPLE
• Who Masked: PARTICIPANT, INVESTIGATOR, OUTCOMES ASSESSOR
• Masking Details: Visually indistinguishable placebo and budesonide nasal sprays will be coded by research staff not connected to the study and pre-packaged for participants. All assays will be performed by personnel who do not know the exposure conditions of individual samples.
• Purpose: BASIC SCIENCE
• Intervention Model: CROSSOVER
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Principal Investigator

Model Details: 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.

Study Record Dates

• First Submitted: March 9, 2020
• First Posted: April 10, 2020
• Study Start: January 7, 2021
• Primary Completion: December 31, 2025
• Study Completion (Estimated): December 31, 2027
• Last Updated: March 27, 2025

Record last verified: 2025-03

Data Sharing

• IPD Sharing: Will not share

Locations

CA (1)