Budesonide for Allergic Disease

(Project Ace Trial)

Overseen By Agnes Yuen, BSc

Age: 18+

Sex: Any

Trial Phase: Phase 4

Sponsor: University of British Columbia

Must not be taking: Systemic corticosteroids, Topical corticosteroids, Antihistamines, Leukotriene antagonists

Disqualifiers: Asthma, Allergic skin conditions, others

Prior Safety Data This treatment has passed at least one previous human trial

Breakthrough Therapy This drug has been fast-tracked for approval by the FDA given its high promise

Compensation: Varies

Number of Visits: Unknown

20 Participants Needed

Trial Summary

What is the purpose of this trial?

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.

Will I have to stop taking my current medications?

Yes, you will need to stop taking certain medications before joining the trial. Specifically, you must stop using systemic corticosteroids 2 months before, topical corticosteroids 2 weeks before, antihistamines 1 week before, and leukotriene antagonists 1 week before the baseline visit.

What data supports the effectiveness of the drug Budesonide Nasal for allergic disease?

Research shows that intranasal budesonide is effective in reducing nasal symptoms in both children and adults with perennial rhinitis (a type of long-lasting nasal allergy). It was found to be more effective than a placebo, with few and minor side effects, making it a safe and effective option for treating nasal allergies. ^{1 2 3 4 5}

Is budesonide safe for treating allergic diseases?

Budesonide, used as a nasal spray, has been studied for safety in both children and adults with allergic rhinitis. Most studies report few and minor side effects, such as headaches and blurred vision, and overall, it is considered safe for long-term use. ^{1 2 3 6 7}

How is the drug Budesonide Nasal unique for treating allergic disease?

Budesonide Nasal is unique because it is a topical corticosteroid that can be administered as an aqueous nasal spray or as a pure powder inhalation, offering flexibility in administration without preservatives or lubricants. It has a rapid onset of action within 12 hours and is effective in reducing nasal symptoms and the need for additional antihistamines. ^{3 8 9 10 11}

Research Team

Christopher Carlsten, MD

Principal Investigator

University of British Columbia

Eligibility Criteria

This trial is for healthy adults aged 18-65 with a clinical diagnosis of allergic rhinitis due to dust mites, grass, or trees. They must have needed treatment during pollen season for the last two years and be able to attend all study visits. Women should not be pregnant/nursing and must use contraception if necessary.

Inclusion Criteria

I am not currently experiencing symptoms of rhinitis.

A nasal allergen challenge resulting in at least five sneezes and/or a recorded score of >2 in either nasal obstruction or runny nose

I have been diagnosed with allergic rhinitis for at least 2 years.

Exclusion Criteria

Subjects allergic to other allergens occurring during the study period

History of asthma

I am not pregnant or nursing.

Timeline

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment Cycle 1

Participants receive either Budesonide or placebo nasal spray, with nasal sampling and symptom questionnaires conducted during in-person visits.

4 weeks

Multiple in-person visits for nasal sampling and questionnaires

Wash-out Period

Participants undergo a wash-out period before starting the second treatment cycle.

2 weeks

Treatment Cycle 2

Participants receive the opposite treatment (Budesonide or placebo) with continued nasal sampling and symptom questionnaires.

4 weeks

Multiple in-person visits for nasal sampling and questionnaires

Follow-up

Participants are monitored for safety and effectiveness after treatment completion.

4 weeks

Treatment Details

Interventions

• Budesonide Nasal

Trial Overview The trial is testing whether Budesonide nasal spray can modify the epigenetic changes caused by allergens in patients with allergic rhinitis. It compares Budesonide's effects against a placebo in reversing these genetic expressions influenced by environmental factors.

Participant Groups

Group I: Budesonide nasal Active Control 1 Intervention

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

Group II: Placebo Placebo Group 1 Intervention

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

Who Is Running the Clinical Trial?

University of British Columbia

Lead Sponsor

Trials

1,506

Recruited

2,528,000+

Genome British Columbia

Industry Sponsor

Trials

13

Recruited

223,000+

Johnson & Johnson Consumer Inc. (J&JCI)

Industry Sponsor

Trials

57

Recruited

5,700+

Findings from Research

From 2007 to 2022, the FDA received 119 reports regarding the off-label use of budesonide nasal irrigation, primarily from patients.

Adverse events associated with this usage included headaches, difficulty breathing (dyspnea), and blurred vision, highlighting potential safety concerns.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Adverse events associated with budesonide nasal irrigation reported to the US Food and Drug Administration: 2007 to 2022. Rathi, VK., Sawicki, NW., Schlosser, RJ., et al.[2023]

In a study involving 202 children aged 6 to 16 with perennial allergic rhinitis, budesonide aqueous nasal spray at a dose of 128 microg once daily was significantly more effective than placebo in improving nasal airflow and reducing symptoms within the first 12 hours.

Budesonide also led to a decrease in eosinophils, which are associated with allergic reactions, and reduced the need for rescue medication, indicating its efficacy in managing allergic rhinitis in children.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Budesonide aqueous nasal spray is an effective treatment in children with perennial allergic rhinitis, with an onset of action within 12 hours. Fokkens, WJ., Cserháti, E., dos Santos, JM., et al.[2019]

Budesonide, a non-halogenated steroid nasal spray, demonstrated a significant and dose-dependent reduction in nasal symptoms such as blockage, discharge, and sneezing in a study of 36 patients with perennial rhinitis.

Long-term use of budesonide (over two years) showed no serious adverse reactions, and monitoring of hematologic parameters and adrenal function indicated it is safe for extended treatment.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

The effect of budesonide in perennial rhinitis. Balle, VH.[2008]

References

1. United States pubmed.ncbi.nlm.nih.gov

Efficacy and safety of intranasal budesonide in the treatment of perennial rhinitis in adults and children. [2007]

2. China pubmed.ncbi.nlm.nih.gov

[Clinical observation on intranasal budesonide in chronic nonallergic rhinitis]. [2014]

3. England pubmed.ncbi.nlm.nih.gov

Safety of nasal budesonide in the long-term treatment of children with perennial rhinitis. [2019]

4. United States pubmed.ncbi.nlm.nih.gov

Effect of nebulized budesonide on decreasing the recurrence of allergic fungal rhinosinusitis. [2018]

5. England pubmed.ncbi.nlm.nih.gov

Effects of orally inhaled budesonide in seasonal allergic rhinitis. [2022]

6. United States pubmed.ncbi.nlm.nih.gov

Adverse events associated with budesonide nasal irrigation reported to the US Food and Drug Administration: 2007 to 2022. [2023]

7. China pubmed.ncbi.nlm.nih.gov

[The efficacy and safety of budesonide inhalation suspension via transnasal nebulization compared with oral corticosteroids in chronic rhinosinusitis with nasal polyps]. [2018]

8. United States pubmed.ncbi.nlm.nih.gov

Budesonide aqueous nasal spray is an effective treatment in children with perennial allergic rhinitis, with an onset of action within 12 hours. [2019]

9. England pubmed.ncbi.nlm.nih.gov

Dry powder inhalation of budesonide in allergic rhinitis. [2019]

10. England pubmed.ncbi.nlm.nih.gov

Budesonide vs Saline Nasal Irrigation in Allergic Rhinitis: A Randomized Placebo-Controlled Trial. [2020]

11. Denmark pubmed.ncbi.nlm.nih.gov

The effect of budesonide in perennial rhinitis. [2008]