Epigenetic Health Benefits of Budesonide

NCT ID: NCT04342039

Last Updated: 2025-03-27

Basic Information

• Recruitment Status: ACTIVE_NOT_RECRUITING
• Clinical Phase: PHASE4
• Total Enrollment: 20 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2021-01-07
• Study Completion Date: 2027-12-31

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.

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.

Conditions

Epigenetic Effects of Intranasal Steroids; Environmental Exposure

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: CROSSOVER
• Primary Study Purpose: BASIC_SCIENCE
• Blinding Strategy: TRIPLE

Study Groups

Placebo

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

Group Type: PLACEBO_COMPARATOR

Placebo

Intervention Type: OTHER

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

Budesonide nasal

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

Group Type: ACTIVE_COMPARATOR

Budesonide Nasal

Intervention Type: DRUG

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

Interventions

Budesonide Nasal

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

Intervention Type: DRUG

Placebo

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

Intervention Type: OTHER

Other Intervention Names

Rhinocort

Eligibility Criteria

Inclusion Criteria

• 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

Exclusion Criteria

• 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.
• 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.)

• Minimum Eligible Age: 18 Years
• Maximum Eligible Age: 65 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

Genome British Columbia

INDUSTRY

Sponsor Role: collaborator

Johnson & Johnson Consumer Inc. (J&JCI)

INDUSTRY

Sponsor Role: collaborator

University of British Columbia

OTHER

Sponsor Role: lead

Responsible Party

Christopher Carlsten

Principal Investigator

Responsibility Role: PRINCIPAL_INVESTIGATOR

Principal Investigators

Christopher Carlsten, MD

Role: PRINCIPAL_INVESTIGATOR

University of British Columbia

Locations

University of British Columbia

Vancouver, British Columbia, Canada

Countries

Canada

Other Identifiers

H20-00414

Identifier Type: -

Identifier Source: org_study_id