Proton Pump Inhibitor (PPI) Response in Eosinophilic Esophagitis Assessed by Transnasal Endoscopy (TNE)

Study Overview
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Brief Summary
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This study will enroll participants who have been diagnosed with Eosinophilic Esophagitis (EoE). Upon study enrollment, the participant will begin a proton pump inhibitor (PPI), Omeprazole 20mg twice daily. After taking Omeprazole for four weeks, the participant will have a Transnasal Endoscopy, and biopsies will be taken to determine the histological change. If the biopsies are abnormal, the participant continues Omeprazole and will undergo another endoscopy at eight weeks. The study aims to determine the percentage of children with Eosinophilic Esophagitis who improve with PPI use and to determine the length of time and effectiveness of PPI therapy in the management of EoE. The investigators hypothesize that following the initiation of PPI for treatment of Eosinophilic Esophagitis, biopsies obtained will show decreasing eosinophil counts at four weeks, which is sooner than the previously reported eight-week period.

Detailed Description
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This study aims to learn more about the subset of children with Eosinophilic Esophagitis (EoE) who are on treatment with a proton pump inhibitor (PPI). EoE is an increasingly common allergic condition of the esophagus for which we have limited treatment options. This study will be helpful in evaluating the minimal time frame required for histological improvement with the use of high dose PPI. The study will enroll participants who have been diagnosed with Eosinophilic Esophagitis (EoE) and are recommended by their physician to begin PPI treatment with Omeprazole 20 mg twice daily. After taking Omeprazole for four weeks, the participant will undergo an unsedated Transnasal Endoscopy (TNE) in the outpatient clinic at Children's Hospital Colorado. TNE is a test in which the doctor inserts a skinny bendable tube with a camera through the nose to look directly into the esophagus (the tube connecting the mouth to the stomach when you swallow) and is an alternative method to assess esophageal mucosa without requiring general anesthesia. Biopsies will be collected during the TNE to determine if there is histological change. If the biopsies are normal, the participant will complete the study. If biopsies are abnormal, and EoE is still active, the participant will continue the Omeprazole and undergo the standard of care endoscopy at eight weeks. The participant will choose the type of endoscopy- unsedated TNE or esophagogastroduodenoscopy (EGD) under anesthesia. Participants will also complete surveys during study enrollment about medication compliance, Eosinophilic Esophagitis symptoms, anxiety, TNE experience, and undergo a physical exam. The investigators hypothesize that following the initiation of PPI for treatment of Eosinophilic Esophagitis, biopsies obtained will show decreasing eosinophil counts at four weeks, which is sooner than the previously reported eight-week period. Results from this study will be generalizable to the pediatric EoE population and the knowledge gained will provide key preliminary data to support clinical recommendations for pediatric EoE patients.

Official Title
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Proton Pump Inhibitor (PPI) Response in Eosinophilic Esophagitis Assessed by Transnasal Endoscopy (TNE)

Conditions
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Eosinophilic Esophagitis

Intervention / Treatment
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* Drug: Omeprazole 20mg BID


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Provide signed and dated informed consent form Male or female, ages 8-22 Current diagnosis of Eosinophilic Esophagitis (≥ 15 eos/HPF) within the last 6 months Able to swallow pills or open capsule to take medication with apple sauce Weight >20kg Willing to undergo unsedated transnasal endoscopy (TNE) Exclusion Criteria: Inability or unwillingness of participant to give written informed consent or comply with study protocol. Have a known bleeding disorder Current topical esophageal corticosteroid or systemic steroid treatment within past 8 weeks No therapy with H2 therapy within the past 16 weeks Planned or anticipated change in the diet during the study duration. Planned or anticipated change in other corticosteroid medications Uncontrolled cough, rhinorrhea, rhinitis obstructing nasal passages, GI illness or determination of significant illness at screening Pregnancy, breast feeding or plans to become pregnant Use of investigational drug within last 16 weeks Allergy to any medications used for procedures Allergy to PPI Past or current medical problems or findings from physical exam or laboratory testing that are not listed above, which, in the opinion of the investigator, may pose additional risks from participation in the study, may interfere with participant's ability to comply with study requirements, or that may impact the quality or interpretation of the data obtained from the study

Ages Eligible for Study
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Minimum Age: 8 Years
Maximum Age: 22 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
Intervention Model: Single Group Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Omeprazole<br>Participants will receive high dose PPI therapy (Omeprazole 20mg twice daily) and will be evaluated for histological improvement. | Drug: Omeprazole 20mg BID<br>* High dose PPI therapy (Omeprazole 20mg twice daily)<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Histological Response at baseline | The histological response will be based on pathologist's review of esophageal biopsies for pediatric participants with Eosinophilic Esophagitis (EoE). EoE diagnosis is identified if there are ≥ 15 eosinophils per high power field (hpf) in the esophagus. | baseline | 
| Change in Histological Response Rate at four weeks | The histological response will be based on pathologist's review of esophageal biopsies for pediatric participants with Eosinophilic Esophagitis (EoE) who are prescribed a high dose proton pump inhibitor, Omeprazole 20 mg twice daily. Biopsies will be evaluated using the EoE histological scoring system. Response will be defined as the peak eosinophil count of < 15 eosinophils per high power field and normal will be defined at 0 eosinophils per high power field. | 4 weeks | 
| Change in Histological Response Rate at eight weeks | The histological response will be based on pathologist's review of esophageal biopsies for pediatric participants with Eosinophilic Esophagitis (EoE) who are prescribed a high dose proton pump inhibitor, Omeprazole 20 mg twice daily. Biopsies will be evaluated using the EoE histological scoring system. Response will be defined as the peak eosinophil count of < 15 eosinophils per high power field and normal will be defined at 0 eosinophils per high power field. | 8 weeks | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| PEESS (Pediatric Eosinophilic Esophagitis Symptom Severity Module) scores at enrollment | The PEESS (Pediatric Eosinophilic Esophagitis (EoE) Symptom Scores) validated assessment tool will be completed by participant and parent at the enrollment visit. PEESS is a metric that seeks to capture EoE specific symptoms directly from children and their parents. Scores range from 0 (never) to 4 (almost always) and each question measures frequency and severity of EoE symptoms in the past month. | At enrollment | 
| PEESS (Pediatric Eosinophilic Esophagitis Symptom Severity Module) scores at four weeks | The PEESS (Pediatric Eosinophilic Esophagitis (EoE) Symptom Scores) validated assessment tool will be completed by participant and parent after four weeks using Omeprazole 20mg twice daily. PEESS is a metric that seeks to capture EoE specific symptoms directly from children and their parents. Scores range from 0 (never) to 4 (almost always) and each question measures frequency and severity of EoE symptoms in the past month. | 4 weeks | 
| PEESS (Pediatric Eosinophilic Esophagitis Symptom Severity Module) scores at eight weeks | The PEESS (Pediatric Eosinophilic Esophagitis (EoE) Symptom Scores) validated assessment tool will be completed by participant and parent after eight weeks using Omeprazole 20mg twice daily. PEESS is a metric that seeks to capture EoE specific symptoms directly from children and their parents. Scores range from 0 (never) to 4 (almost always) and each question measures frequency and severity of EoE symptoms in the past month. | 8 weeks | 
| Eosinophilic Esophagitis Histology Scoring System (HSS) scores at enrollment | The EoE HSS provides a method to objectively assess histology change in esophageal biopsies beyond eosinophil count. The HSS evaluates eight features: eosinophil density, basal zone hyperplasia, eosinophil abscesses, eosinophil surface layering, dilated intercellular spaces (DIS), surface epithelial alteration, dyskeratotic epithelial cells, and lamina propria fibrosis. The study pathologist will review the historical esophageal biopsies using the HSS. | At enrollment | 
| Eosinophilic Esophagitis Histology Scoring System (HSS) scores at four weeks | The EoE HSS provides a method to objectively assess histology change in esophageal biopsies beyond eosinophil count. The HSS evaluates eight features: eosinophil density, basal zone hyperplasia, eosinophil abscesses, eosinophil surface layering, dilated intercellular spaces (DIS), surface epithelial alteration, dyskeratotic epithelial cells, and lamina propria fibrosis. The study pathologist will review the participant's esophageal biopsies collected after four weeks of Omeprazole 20mg twice daily using the HSS. | 4 weeks | 
| Eosinophilic Esophagitis Histology Scoring System (HSS) scores at eight weeks | The EoE HSS provides a method to objectively assess histology change in esophageal biopsies beyond eosinophil count. The HSS evaluates eight features: eosinophil density, basal zone hyperplasia, eosinophil abscesses, eosinophil surface layering, dilated intercellular spaces (DIS), surface epithelial alteration, dyskeratotic epithelial cells, and lamina propria fibrosis. The study pathologist will review the participant's esophageal biopsies collected after eight weeks of Omeprazole 20mg twice daily using the HSS. | 8 weeks | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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EoE, PPI, Proton Pump Inhibitor, Omeprazole, eosinophil, TNE, Transnasal Endoscopy, Esophageal Diseases, Esophagitis, Gastrointestinal Diseases, Eosinophilia, Gastroenteritis, Eosinophilic Oesophagitis, Transnasal Esophagogastroduodenoscopy, Transnasal Esophagoscopy