The Role Of Gastroesophageal Reflux Disease (GERD) in Eosinophilic Esophagitis

Study Overview
=================
Brief Summary
-----------------
The primary aim of this study was to determine the proportion of patients with esophageal eosinophilic infiltration that have objective (measurable) evidence of gastroesophageal reflux disease (GERD). This study was also done to see if patients that have eosinophilic esophagitis (EE) and GERD would receive relief from taking the medication Nexium or a steroid called Pulmicort. The study also evaluated the accuracy of pH monitoring (acid exposure) within the esophagus as a predictor of endoscopic, histological and symptomatic response in patients with EE.

Detailed Description
-----------------
Hypotheses: There is a subset of patients with the diagnosis of EE who also have GERD. Patients with both EE and GERD will respond symptomatically and histologically to aggressive gastric acid suppression with a proton pump inhibitor as monotherapy. Swallowed budesonide suspension is effective in treating patients with EE who do not have evidence of GERD. Participants were randomized based on results of a 24 hour pH study, which determined the average percent time the distal esophagus was exposed to a pH of less than than 4. Subjects with a positive pH result were randomized to esomeprazole or randomized to budesonide, if there was a negative pH result. Studies were interpreted by a single gastroenterologist experienced in reading esophageal pH studies. The percent time the pH monitor detected a pH less than 4 was recorded and an esophageal pH of less than 4 for 4% or greater of the study time was considered abnormal. Note: pH is a measure of acidity or alkalinity (lower numbers are more acid, higher numbers are more alkaline). Those subjects with GERD (positive pH result) received gastric acid-suppressing medication (esomeprazole 40 mg, twice daily) for 6 weeks. Subjects who did not have GERD (negative pH result) were treated with a corticosteroid designed to coat the esophagus (budesonide suspension 1 mg twice daily) for six weeks. Response to treatment was assessed by esophageal histology and symptoms.

Official Title
-----------------
The Role Of Gastroesophageal Reflux Disease (GERD) in Eosinophilic Esophagitis

Conditions
-----------------
EE, Eosinophilic Esophagitis, Gastroesophageal Reflux Disease, GERD

Intervention / Treatment
-----------------
* Drug: Esomeprazole
* Drug: Budesonide


Participation Criteria
=================
Eligibility Criteria
-----------------
Inclusion Criteria: Patients ages 18-80. Patients who carry the diagnosis of Eosinophilic Esophagitis (EE) based on esophageal biopsies obtained within 18 months prior to enrollment with greater than 15 eosinophils (eos) per high power field (hpf) (400 X magnification). Patients who have moderate, severe, or very severe problems swallowing. Exclusion Criteria: Patients who are currently being treated for EE. Patients who have used topical or systemic corticosteroid therapy for any reason over the past 4 weeks. Patients who have been treated with acid-suppressing medications (Proton Pump Inhibitor or H2 receptor antagonists) within 4 weeks prior to enrollment. Patients with known allergies or hypersensitivity to proton-pump inhibitors or corticosteroids. Patients who have contraindications to the procurement of biopsies including patients how have known bleeding disorders, a history of bleeding diathesis, or who are currently using warfarin or clopidogrel. Patients who have a contraindication to the performance of an esophagogastroduodenoscopy (EGD) including previous cardiopulmonary arrest during an endoscopic procedure. Patients who have contraindications to the performance of ambulatory impedance 24-hour pH testing including patients with oropharyngeal abnormalities that would prohibit the safe passage of the transnasal catheter and patients who are currently using warfarin, have a history of bleeding disorders or bleeding diatheses. Patients who are pregnant.

Ages Eligible for Study
-----------------
Minimum Age: 18 Years
Maximum Age: 80 Years

Sexes Eligible for Study
-----------------
All

Accepts Healthy Volunteers
-----------------
No

Study Plan
=================
How is the study designed?
-----------------

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: Esomeprazole<br>Proton pump inhibitor; Nexium 40mg capsule taken twice daily by mouth for 6 weeks for subjects with positive 24 hour pH study (GERD) | Drug: Esomeprazole<br>* Proton pump inhibitor; Nexium 40mg capsule taken twice daily by mouth for 6 weeks<br>* Other names: Nexium;|
| Active Comparator: Budesonide<br>Corticosteroid therapy; oral viscous Pulmicort Respules 1 gram taken by mouth orally twice daily (mixed with 1 gram packet of Sucralose [Splenda-registered trademark]) for 6 weeks in subjects with negative 24 hour pH studies (without GERD) | Drug: Budesonide<br>* Corticosteroid therapy; oral viscous Pulmicort Respules 1 gram taken by mouth orally twice daily (mixed with 1 gram packet of Sucralose [Splenda-registered trademark]) for 6 weeks in subjects with negative 24 hour pH studies (without GERD)<br>* Other names: Pulmicort;|

What is the study measuring?
-----------------
Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Histological Response to Treatment | Subjects with Esophageal eosinophilia experiencing a histological response to treatment. Subjects were considered to have histological response to treatment if both sets of biopsies (from the distal and mid-esophagus) had, on average, less than 5 eosinophils per high power field (eos/hpf) at the 6-month biopsies. | Baseline, 6 months | 
| Symptomatic Response to Treatment | Subjects with Esophageal eosinophilia experiencing a response in their dysphagia symptoms to treatment. Symptomatic improvement in symptoms was defined as a score of at least two levels lower than the baseline dysphagia symptom question on the Mayo Dysphagia Questionnaire-30 days (MDQ-30). Dysphagia symptoms were determined based on the MDQ-30 question: 'How would you rate the severity of your trouble swallowing in the past 30 days' with a 5 point scale ranging from 'does not bother me at all' to 'very severe, markedly affects my lifestyle'. Patients must have marked a score of 3 or higher corresponding to 'Moderate, cannot be ignored, but does not affect my lifestyle' to be included in the study. | Baseline, 6 months | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Change in Dysphagia Symptoms in Subjects With Histological Response to Treatment | Dysphagia symptoms were determined based on the Mayo Dysphagia Questionnaire-30 days (MDQ-30), using the question: 'How would you rate the severity of your trouble swallowing in the past 30 days' with a 5 point scale ranging from 'does not bother me at all' to 'very severe, markedly affects my lifestyle'. Symptomatic improvement was defined as only an improvement of 2 levels on this question. | Baseline, 6 months | 
| Change in Dysphagia Symptoms in Subjects With Non-significant Histological Response to Treatment | Dysphagia symptoms were determined based on the Mayo Dysphagia Questionnaire-30 days (MDQ-30), using the question: 'How would you rate the severity of your trouble swallowing in the past 30 days' with a 5 point scale ranging from 'does not bother me at all' to 'very severe, markedly affects my lifestyle'. Patients must have marked a score of 3 or higher corresponding to 'Moderate, cannot be ignored, but does not affect my lifestyle' to be included in the study. | Baseline, 6 months | 
| Participants With Presence of Esophageal Rings/Furrows at Six Month Endoscopy | Multiple concentric rings or furrows of the esophagus is an endoscopic finding traditionally ascribed to eosinophilic esophagitis. | Baseline, 6 months | 
| Participants With Presence of Erosive Esophagitis at Six Month Endoscopy |  | Baseline, 6 months |