A Study of Flovent in Patients With Eosinophilic Esophagitis

Study Overview
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Brief Summary
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The purpose of this study is to test the effects (both good and bad) of high dose swallowed fluticasone propionate (Flovent) in subjects with eosinophilic esophagitis (EoE).

Official Title
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A Double Blinded, Randomized Trial of Swallowed 1760mcg Fluticasone Propionate Versus Placebo in the Treatment of Eosinophilic Esophagitis

Conditions
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Eosinophilic Esophagitis

Intervention / Treatment
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* Drug: Flovent
* Other: Placebo


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Signed informed consent for study by subject, or parent/guardian if subject is a minor. Assent will be obtained from all minors 11 years of age and older. Histological findings on esophageal biopsy to include peak eosinophil density ≥ 24 per high power field (400x) in the proximal or distal esophagus validated by a pathologist at CCHMC. Allergy evaluation including skin-prick testing with multiple food antigens to ensure elimination diet is not indicated. Have undergone a minimum 3 months of elimination diet as indicated by skin-prick testing without detectable resolution by repeat endoscopy with biopsies demonstrating persistent EE OR subject/parental refusal to follow elimination diet. If the subject/parent refuses the elimination diet, they are eligible for this study. Treatment with a proton-pump inhibitor for at least two months (rounded to nearest month) prior to endoscopy OR failure of histological improvement as defined by < 1 eosinophil per HPF after 2 month (rounded to nearest month) trial of proton pump inhibitor documented by prior endoscopy. The PPI must be used prior to endoscopy to rule out the possibility of GERD. Exclusion Criteria: History of poor tolerance to Fluticasone Propionate (FP), as defined as multiple episodes of oral candidiasis, hypothalamic-pituitary-adrenal axis suppression as evidenced by signs of Cushing syndrome, headaches, or increased respiratory infections during exposure to Flovent Unable to cooperate with use of MDI Pregnant females Concurrent or recent (within 3 months) use of systemic corticosteroids. Unable to swallow medicines (i.e., fed only by gastrostomy tube). Comorbid eosinophilic disorders. Previously treated with swallowed glucocorticoid for EE within 3 months of the screening visit. Nasal glucocorticoids taken for EE are permitted.

Ages Eligible for Study
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Minimum Age: 3 Years
Maximum Age: 30 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: Quadruple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Flovent 1760 mcg<br>Fluticasone propionate 880 mcg twice daily for 3 months | Drug: Flovent<br>* 1760 mcg daily<br>* Other names: Fluticasone propionate;|
| Placebo Comparator: Placebo<br>Placebo twice daily for 3 months | Other: Placebo<br>* Placebo<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Percentage of Participants Who Attained Remission. | Remission is considered achieved when the highest eosinophil count per high power field (hpf) in all esophageal biopsies is </= 1 eosinophil/hpf after 3 months of therapy. | 3 months | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Percent of Participants With Decreased Cortisol Levels After 3 Months | Blood and saliva cortisol was measured and compared to reference range at 3 months. Participants with measures below the reference range were considered decreased. | 3 months | 
| Association of Subject Age, Body Mass Index Z-score, and Allergic Status to Response to Flovent | Strength of the association (odds ratio) of age, body mass index (BMI) z-score , and allergic status with response to Flovent. Allergic status is defined as a history of allergic disease (allergic rhinitis, hay fever, atopic dermatitis, eczema, food anaphylaxis, asthma, or positive skin prick tests). Response is defined as <= 1 eosinophil/high power field in esophageal biopsies. | 3 months | 
| EoE Score After 3 Months | The gene expression profile is associated with an EoE score algorithm reflecting disease status and severity in a quantifiable number - called the EoE score, based on a core set of 77 diagnostic genes. The EoE score was calculated for Flovent responders and placebo. Higher scores indicate normalization of genes associated with inflammation and fibrosis (disease severity). Therefore higher scores mean a better outcome. The minimum score is zero. There is no maximum score. | 3 months | 
| Association of Compliance With Therapy and Response to Flovent | Odds ratio was determined to show the strength of the association between compliance with the drug therapy and response to the drug therapy | 3 months | 
| Percent of Participants With Abdominal Pain After Therapy | Percent of participants responding that they experienced abdominal pain (i.e. they did not respond never) after therapy. Responses were dichotomized into Never and sometimes. | 3 months | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Eosinophilic Esophagitis