Eosinophilic Esophagitis
Conditions
Keywords
Eosinophilic Esophagitis
Brief summary
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).
Interventions
DRUGFlovent
1760 mcg daily
OTHERPlacebo
Placebo
Sponsors
Marc Rothenberg, MD
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
QUADRUPLE (Subject, Caregiver, Investigator, Outcomes Assessor)
Eligibility
Sex/Gender
ALL
Age
3 Years to 30 Years
Healthy volunteers
No
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.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Percentage of Participants Who Attained Remission. | 3 months | 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. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Percent of Participants With Decreased Cortisol Levels After 3 Months | 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. |
| Association of Subject Age, Body Mass Index Z-score, and Allergic Status to Response to Flovent | 3 months | 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. |
| EoE Score After 3 Months | 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. |
| Association of Compliance With Therapy and Response to Flovent | 3 months | Odds ratio was determined to show the strength of the association between compliance with the drug therapy and response to the drug therapy |
| Percent of Participants With Abdominal Pain After Therapy | 3 months | 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. |
Countries
United States
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| Flovent 1760 mcg Drug
Flovent : 880 mcg twice daily | 28 |
| Placebo Placebo twice daily | 14 |
| Total | 42 |
Baseline characteristics
| Characteristic | Placebo | Flovent 1760 mcg | Total |
|---|---|---|---|
| Age, Categorical <=18 years | 12 Participants | 26 Participants | 38 Participants |
| Age, Categorical >=65 years | 0 Participants | 0 Participants | 0 Participants |
| Age, Categorical Between 18 and 65 years | 2 Participants | 2 Participants | 4 Participants |
| Age, Continuous | 13.54 years STANDARD_DEVIATION 7.11 | 12.15 years STANDARD_DEVIATION 6.42 | 12.6 years STANDARD_DEVIATION 6.6 |
| Region of Enrollment United States | 14 participants | 28 participants | 42 participants |
| Sex: Female, Male Female | 1 Participants | 6 Participants | 7 Participants |
| Sex: Female, Male Male | 13 Participants | 22 Participants | 35 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | 0 / 28 | 0 / 14 |
| other Total, other adverse events | 19 / 28 | 9 / 14 |
| serious Total, serious adverse events | 0 / 28 | 0 / 14 |
Outcome results
Primary
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.
Time frame: 3 months
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Flovent 1760 mcg | Percentage of Participants Who Attained Remission. | 65.2 percentage of participants |
| Placebo | Percentage of Participants Who Attained Remission. | 0 percentage of participants |
Secondary
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
Time frame: 3 months
Population: Analysis population is restricted only to those that were given Flovent for the purpose of determining whether compliance with therapy was associated with response to drug
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Flovent 1760 mcg | Association of Compliance With Therapy and Response to Flovent | 1.037 Odds Ratio |
Secondary
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.
Time frame: 3 months
Population: Analysis population is restricted only to those that were given Flovent for the purpose of determining whether these specific variables are associated with response to drug
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Flovent 1760 mcg | Association of Subject Age, Body Mass Index Z-score, and Allergic Status to Response to Flovent | Odds Ratio for Allergic Status | 0.572 Odds Ratio |
| Flovent 1760 mcg | Association of Subject Age, Body Mass Index Z-score, and Allergic Status to Response to Flovent | Odds Ratio for Age | 0.907 Odds Ratio |
| Flovent 1760 mcg | Association of Subject Age, Body Mass Index Z-score, and Allergic Status to Response to Flovent | Odds Ratio for BMI Z-Score | 0.541 Odds Ratio |
Secondary
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.
Time frame: 3 months
Population: Population includes only responders to Flovent and all participants finishing the study on Placebo.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Flovent 1760 mcg | EoE Score After 3 Months | 382 score on a scale | Standard Deviation 47 |
| Placebo | EoE Score After 3 Months | 152 score on a scale | Standard Deviation 119 |
Secondary
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.
Time frame: 3 months
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Flovent 1760 mcg | Percent of Participants With Abdominal Pain After Therapy | 63 percentage of participants |
| Placebo | Percent of Participants With Abdominal Pain After Therapy | 50 percentage of participants |
Secondary
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.
Time frame: 3 months
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Flovent 1760 mcg | Percent of Participants With Decreased Cortisol Levels After 3 Months | 17.4 percentage of participants |
| Placebo | Percent of Participants With Decreased Cortisol Levels After 3 Months | 0 percentage of participants |