EoE RCT Fluticasone and Omeprazole vs Fluticasone Alone

Study Overview
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Brief Summary
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The purpose of this study is to evaluate the efficacy of combination therapy with omeprazole and swallowed fluticasone vs fluticasone therapy and placebo in the treatment of Eosinophilic Esophagitis (EoE) in children and adults. This study will be a double-blinded, randomized controlled trial. The primary outcome measured will be histologic assessment of esophageal tissue biopsies measuring number of eosinophils per high power field (eos/hpf). Secondary outcomes will be endoscopic findings and symptomatic changes following therapy using validated endoscopic scoring measures and participant surveys, respectively.

Detailed Description
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Subjects that meet study inclusion criteria will be recruited from the Adult and Pediatric Gastroenterology clinics at Walter Reed National Military Medical Center through routine clinic visits, will meet with an investigator, and complete informed consent/assent. The participants will then complete a validated clinical symptom reporting tool - the Eosinophilic Esophagitis symptom activity index (EEsAI) for age 18 and above, or the Pediatric Quality of Life Inventory (PedsQL) for age 6-17yrs - and have their initial Esophagogastroduodenoscopy (EGD) images evaluated via a validated Endoscopic Reference Score (EREFS). Esophageal biopsies taken at the patient's initial EGD will be assessed by 2 designated blinded pathologists to record the number of eosinophils per high power field (HPF), as well as perform tissue immunohistochemical staining for eotaxin-3. Participants will be block randomized to treatment or control groups and complete 8 weeks of therapy, with a phone follow up at 4 weeks for medication compliance. At the completion of 8 weeks of therapy, the participants will have repeat EGD to assess for mucosal healing, which is the standard of care in the treatment of EoE. At this EGD, the images will be assigned an EREFS and the biopsies will be evaluated for eosinophils per high powered field and eotaxin-3 staining. The patient will also complete an EEsAI or PedsQL. This procedure will end the 8 week study period.

Official Title
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Randomized Controlled Trial Comparing Fluticasone Plus Omeprazole With Fluticasone Alone for Eosinophilic Esophagitis

Conditions
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Eosinophilic Esophagitis

Intervention / Treatment
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* Diagnostic Test: Retrospective evaluation of endoscopy prior to study drug
* Other: Symptom Survey
* Other: Medication Compliance Phone Call
* Diagnostic Test: Endoscopy while on study drug
* Other: Symptom Survey
* Drug: Fluticasone
* Drug: Omeprazole
* Drug: Placebo oral capsule


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: age 6 to 60 years old DEERS (defense enrollment eligibility reporting system) eligible diagnosis of eosinophilic esophagitis Exclusion Criteria: Outside of age range Co-existing inflammatory gastroenterologic condition such as celiac disease, eosinophilic esophagitis, or inflammatory bowel disease. Concurrent use of oral steroids Pregnancy Refusal to undergo endoscopy

Ages Eligible for Study
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Minimum Age: 6 Years
Maximum Age: 60 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: Other
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Quadruple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Fluticasone and omeprazole<br>These patients will be prescribed swallowed fluticasone and omeprazole to be taken together for the 8 week period. Dosing will be based on weight and age. Primary outcome measure will be the change in esophageal biopsy histology, or number of eosinophils per high powered field, from week 0 to week 8. Secondary outcomes will include changes in the following variables between week 0 and 8: eotaxin staining of the esophageal biopsy tissue, endoscopic scoring from photos of the esophagus obtained during endoscopy, and symptom scoring based on surveys. | Diagnostic Test: Retrospective evaluation of endoscopy prior to study drug<br>* Once enrolled, the patient's original endoscopy will be evaluated including the images from the EGD and the biopsies for eotaxin 3 staining and eosinophilic burden.<br>Other: Symptom Survey<br>* Patient will complete symptom survey prior to starting the study drugs.<br>Other: Medication Compliance Phone Call<br>* The patient will receive a phone call at 4 weeks to evaluate medication compliance including the number on the inhaler and the number of pills remaining in the container.<br>Diagnostic Test: Endoscopy while on study drug<br>* Endoscopy will be performed after 8 weeks of therapy. Endoscopic scoring will be assigned and the histology will be evaluated, including eotaxin 3 staining. The change in eosinophil count and eotaxin staining will be measured.<br>Other: Symptom Survey<br>* The patient will complete a symptom survey after 8 weeks on the study drugs, and the change in survey score will be measured.<br>Drug: Fluticasone<br>* Participants in the experimental and placebo arms will be given swallowed fluticasone for an 8 week course. Doses determined by age and weight.<br>Drug: Omeprazole<br>* The participants in the experimental arm will be given oral omprazole capsules for an 8 week period (along with the swallowed fluticasone). Doses determined by age and weight.<br>|
| Placebo Comparator: Fluticasone and placebo<br>These patients will be prescribed swallowed fluticasone and a placebo medication that appears identical to omeprazole to be taken together for an 8 week period. Dosing will be based on weight and age. Primary outcome measure will be the change in esophageal biopsy histology, or number of eosinophils per high powered field, from week 0 to week 8. Secondary outcomes will include changes in the following variables between week 0 and 8: eotaxin staining of the esophageal biopsy tissue, endoscopic scoring from photos of the esophagus obtained during endoscopy, and symptom scoring based on surveys. | Diagnostic Test: Retrospective evaluation of endoscopy prior to study drug<br>* Once enrolled, the patient's original endoscopy will be evaluated including the images from the EGD and the biopsies for eotaxin 3 staining and eosinophilic burden.<br>Other: Symptom Survey<br>* Patient will complete symptom survey prior to starting the study drugs.<br>Other: Medication Compliance Phone Call<br>* The patient will receive a phone call at 4 weeks to evaluate medication compliance including the number on the inhaler and the number of pills remaining in the container.<br>Diagnostic Test: Endoscopy while on study drug<br>* Endoscopy will be performed after 8 weeks of therapy. Endoscopic scoring will be assigned and the histology will be evaluated, including eotaxin 3 staining. The change in eosinophil count and eotaxin staining will be measured.<br>Other: Symptom Survey<br>* The patient will complete a symptom survey after 8 weeks on the study drugs, and the change in survey score will be measured.<br>Drug: Fluticasone<br>* Participants in the experimental and placebo arms will be given swallowed fluticasone for an 8 week course. Doses determined by age and weight.<br>Drug: Placebo oral capsule<br>* The participants in the placebo arm will be given placebo capsules for an 8 week period (along with the swallowed fluticasone). Number of pills determined by age and weight (to match omeprazole dosing).<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Change in esophageal eosinophilia | The number of eosinophils per high powered field will be counted by participating pathologist. | There will be one at week 0 and week 8. | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Change in Endoscopic Reference Score | Endoscopic appearance will be evaluated with a validated scoring method: Minimum score 0, maximum score 10. Scores come from 5 outcomes: Fixed rings (0-3 points), exudates (0-2 points), furrows (0-2 points), edema (0-2 points), stricture (0-1 points). | This will be done at week 0 and week 8 | 
| Change in Symptom Scoring | Clinical changes will be evaluated by either one of 2 validated tools: Eosinophilic Esophagitis symptom activity index (EEsAI) for age 18 and above, or the Pediatric Quality of Life Inventory (PedsQL) for age 6-17yrs. Both of these tools are considered proprietary and we have permission from the companies to use this scoring system for research - and their grading scales were provided. Copyright for PedsQL - JW Varni 1998. Confidentiality for EEsAI scoring - EEsAI Study Group at the University of Bern. | Week 0 and week 8 |