Flunisolide HFA in Children With Small Airway Disease

Study Overview
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Brief Summary
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The purpose of this study is to see how two doses of Flunisolide HFA (an FDA approved inhaled medication to treat asthma) affect the small airways in children with asthma.

Detailed Description
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This is a prospective, randomized, parallel, open label study. The primary aim is to compare the average change in spirometric values (Forced expiratory volume 1 (FEV1) and Forced Expiratory Flow 25-75% (FEF 25-75%) and Impulse Oscillometry System (IOS) values (Resistance at 5 Hz (R5), Resistance at 20 Hz (R20), Area of reactance (AX), Resonant frequency (Fres)) from baseline to week 6 from participants randomized flunisolide hydrofluoroalkane (HFA) 1 inhalation BID and to flunisolide HFA 2 inhalations BID. The change in scores from baseline to six week follow up will initially be compared using paired t-tests and Chi-squared tests for trend. Repeated measurements will be analyzed using generalized linear mixed-effects regression modeling (GLMM) techniques. For continuous outcomes (e.g. FEV1, FEF 25-75%, Fres, reactance at 5 Hz (X5), AX, R5-R20). The identity link function and normal distribution will be used. For count data (e.g., use of Beta-agonists, episodes of coughing, episodes of wheezing, etc.) the log link function and the Poisson distribution will be used. If we dichotomize outcomes (e.g., a Beta-agonist was used, coughing occurred, etc.) the logit link function and Bernoulli distribution will be used.

Official Title
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Flunisolide HFA in Children With Small Airway Disease

Conditions
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Childhood Asthma

Intervention / Treatment
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* Drug: Flunisolide HFA


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Diagnosis of asthma Informed consent by parent or legal guardian 6 years to 18 years of age at screening visit ability to comply with medication use, study visits and study procedures as judged by the site investigator FEF 25-75% <65% of predicted as a marker for small airway disease Exclusion Criteria: Acute wheezing at screening visit or at Baseline visit Acute intercurrent respiratory infection, defined as an increase in cough, wheezing, or respiratory rate with onset in 1 week preceding screening visit or 3 weeks preceding baseline visit Oxygen saturation <95% at screening visit or at Baseline visit Clinically significant upper airway obstruction as determined by the Site Investigator (e.g. severe laryngomalacia, markedly enlarged tonsils, significant snoring, diagnosed obstructive sleep apnea. Severe gastroesophageal reflux, defined as persistent frequent emesis despite anti-reflux therapy Physical findings that would compromise the safety of the subject or the quality of the study data as determined by site investigator Inhaled Corticosteroids (ICS) use within 7 days of Baseline visit; systemic steroids within 30 days Cystic Fibrosis, Interstitial lung disease (ILD) history of severe Bronchopulmonary dysplasia (BPD) or other underling significant respiratory disease apart from asthma Potential subjects who are pregnant may not enroll in the study

Ages Eligible for Study
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Minimum Age: 6 Years
Maximum Age: 18 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: Parallel Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Active Comparator: Flunisolide 160 mcg per day<br>Patients will receive inhaled Flunisolide HFA 80 mcg twice per day for a total of 160 mcg per day over the 6 week study period | Drug: Flunisolide HFA<br> <br> |
| Active Comparator: Flunisolide 320 mcg per day<br>Patients will receive inhaled Flunisolide HFA 160 mcg twice per day for a total of 320 mcg per day over the 6 week study period | Drug: Flunisolide HFA<br> <br> |

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Spirometry Forced Expiratory Volume 1 (FEV1) After Flunisolide | the most used outcome in respiratory studies | Before and after treatment at baseline and six week followup | 
| Impulse Oscillometry (IOS) Area of Reactance (AX) After Flunisolide Treatment | A composite measure of small airway dysfunction. A reduction in IOS scores indicate an improvement. | Baseline and six week followup | 
| Spirometry Forced Expiratory Flow 25-75% (FEF 25-75%) | Indirectly assess small airway function. | baseline and six week followup | 
| Impulse Oscillometry (IOS) Resistance 5 (R5) | Resistance of the respiratory system at 5 Hz is a measure of total airway resistance. Elevated value is indicative of respiratory dysfunction. | initial visit and six week followup |