Steroid Sparing Effect of Nasal Corticosteroid In Asthma And Rhinitis

Study Overview
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Brief Summary
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Up to 40% of patients with asthma have allergic rhinitis and treatment of nasal airway inflammation with topical steroids improves the twitchiness of the airways (hyperresponsiveness) and overall asthma control. The use of inhaled corticosteroids reduces symptoms, severity of asthma attacks, improves quality of life, and reduces asthma related deaths. Similarly, treatment of rhinitis with nasal steroids reduces symptoms and improves quality of life. While there is evidence that combined treatment of the nose and the lungs with topical steroids improves symptoms and underlying inflammation, it is unclear whether such control can be achieved using a smaller dose of inhaled steroid in combination with nasal steroid. It is therefore the intention of this study to evaluate if combination steroid therapy (nose and lungs) has a steroid sparing effect in patients with asthma and rhinitis using sensitive markers of airway inflammation.

Official Title
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A Proof Of Concept Study To Assess The Steroid Sparing Effect Of Combined Nasal And Inhaled Corticosteroid In Patients With Asthma And Persistent Rhinitis

Conditions
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Asthma, Allergic Rhinitis

Intervention / Treatment
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* Drug: Fluticasone Evohaler pMDI
* Drug: Placebo
* Drug: Fluticasone Evohaler
* Drug: Placebo intranasal spray
* Drug: fluticasone propionate (Flixonase®)


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Mild to moderate atopic asthmatics with FEV1 ≥ 60% on ≤ 1000 ug BDP and concomitant persistent allergic rhinitis (SPT +ve and PC20 < 4 mg/ml) Male or female aged 18-65 years Informed Consent Ability to comply with the requirements of the protocol Exclusion Criteria: Severe asthmatics as defined by an FEV1 ≤ 60% or PEF variability > 30% or with continual daytime or nocturnal symptoms. Nasal Polyposis grade 2/3, deviated nasal septum ≥ 50% The use of oral corticosteroids within the last 3 months Recent respiratory tract infection (2 months) Significant concomitant respiratory disease Any other significant medical condition or investigation which may jeopardise the safety of the participant or the conduct of the protocol Any significant abnormal laboratory result as deemed by the investigators Pregnancy, planned pregnancy or lactation Known or suspected contra-indication to any of the IMP's Concomitant use of medicines (prescribed, over the counter or herbal) that may interfere with the trial

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 65 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Crossover Assignment
Masking: Quadruple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Low Dose<br>One puff of inhaled Fluticasone Evohaler pMDI 50 µg twice a day (Total FP dose 100 µg) and 1 puff of inhaled Placebo twice a day with placebo intranasal spray 2 squirts each nostril once a day. | Drug: Fluticasone Evohaler pMDI<br>* One puff of inhaled Fluticasone Evohaler pMDI 50 µg twice a day (Total FP dose 100 µg)<br>Drug: Placebo<br>* 1 puff of inhaled Placebo twice a day<br>Drug: Placebo intranasal spray<br>* placebo intranasal spray 2 squirts each nostril once a day<br>|
| Experimental: Combined<br>One puff of inhaled fluticasone propionate Evohaler pMDI 50 µg twice a day (Total daily FP dose 100 µg) and 1 puffs of Placebo twice a day with intranasal fluticasone propionate (Flixonase®) 50ug 2 squirts each nostril once a day (i.e. total intranasal FP daily dose 200ug). | Drug: Fluticasone Evohaler pMDI<br>* One puff of inhaled Fluticasone Evohaler pMDI 50 µg twice a day (Total FP dose 100 µg)<br>Drug: Placebo<br>* 1 puff of inhaled Placebo twice a day<br>Drug: fluticasone propionate (Flixonase®)<br>* intranasal fluticasone propionate (Flixonase®) 50ug 2 squirts<br>|
| Experimental: High dose<br>One puff of inhaled Fluticasone Evohaler 250µg twice a day (Total daily FP dose 500µg) and 1 puff of inhaled placebo twice a day with placebo intranasal spray 2 squirts each nostril once a day. | Drug: Placebo<br>* 1 puff of inhaled Placebo twice a day<br>Drug: Fluticasone Evohaler<br>* One puff of inhaled Fluticasone Evohaler 250µg twice a day (Total daily FP dose 500µg)<br>Drug: Placebo intranasal spray<br>* placebo intranasal spray 2 squirts each nostril once a day<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| methacholine PC20 |  | 0, 2, 4, 6, 8, 10, 12 weeks | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Spirometry |  | 0, 2, 4, 6, 8, 10, 12 weeks | 
| Juniper AQLQ |  | 0, 2, 4, 6, 8, 10, 12 weeks | 
| Fractionated Nitric Oxide |  | 0, 2, 4, 6, 8, 10, 12 weeks | 
| serum ECP |  | 0, 2, 4, 6, 8, 10, 12 weeks | 
| blood eosinophils |  | 0, 2, 4, 6, 8, 10, 12 weeks | 
| Overnight urinary cortisol creatinine |  | 0, 2, 4, 6, 8, 10, 12 weeks | 
| Peak Nasal Inspiratory Flow rate |  | 0, 2, 4, 6, 8, 10, 12 weeks | 
| Nasal Nitric Oxide |  | 0, 2, 4, 6, 8, 10, 12 weeks | 
| Juniper mini RQLQ |  | 0, 2, 4, 6, 8, 10, 12 weeks | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Asthma, Allergic rhinitis, fluticasone, methacholine