Prostaglandin and Cannabinoid Receptors in EoE

Study Overview
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Brief Summary
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The purpose of this study is to investigate prostaglandin and cannabinoid receptors and their endogenous ligands in eosinophilic esophagitis (EoE). A prostaglandin D2 receptor antagonist has been shown to improve disease symptoms suggesting a regulatory role for bioactive lipids in EoE. Prostaglandin D2 and E2, and endocannabinoids are lipid mediators that govern the functional and inflammatory behavior of immune cells critical for EoE development. The prostaglandin D2 and E2 receptor axis, and the components of the endocannabinoid may be involved in the pathogenesis of EoE.

Detailed Description
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Prostaglandin D2 and E2 receptors, and components of the endocannabinoid system (cannabinoid receptors and endocannabinoid-metabolizing enzymes) are examined in mucosal esophageal biopsies and blood leukocytes from EoE patients (acute and in remission), individuals with gastroesophageal reflux and from individuals with no esophageal disease. Expression of these components are compared between all cohorts by polymerase chain reaction, Western blots, flow cytometry and immunohistochemical methods. EoE disease activity is evaluated by determining a symptom score and the number of eosinophils per high-power field (hpf) in histologic sections of mucosal biopsies. Additionally, an Endoscopic Reference Score (EREFS) is used. Disease activity is correlated with cannabinoid/prostaglandin D2 and E2 receptor expression. Blood is collected and immediately processed for flow cytometric experiments. Prostaglandins and endocannabinoids are measured in plasma and esophageal mucosal biopsy samples of all cohorts by mass spectrometry.

Official Title
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Prostaglandin and Cannabinoid Receptors in the Development of Eosinophilic Esophagitis

Conditions
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Eosinophilic Esophagitis (EoE)

Intervention / Treatment
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* Other: Biopsy samples
* Other: Blood samples


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: diagnosed or suspected EoE or GERD without esophageal diseases with signed informed consent Exclusion Criteria: viral or parasitic diseases (e.g. herpes, candidiasis) eosinophilic gastroenteritis, hypereosinophilic syndrome, Crohn's disease autoimmune diseases unable to give informed consent immunosuppressive therapy

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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Accepts Healthy Volunteers

Study Plan
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How is the study designed?
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Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| EoE group<br>Patients with confirmed eosinophilic esophagitis | Other: Biopsy samples<br>* Esophageal mucosal biopsies are collected during gastroscopy<br>Other: Blood samples<br>* Blood will be drawn by venipuncture into citrate- or ethylenediaminetetraacetic acid (EDTA)-containing vacutainer tubes and into serum tubes<br>|
| GERD group<br>Patients with gastro-esophageal reﬂux disease | Other: Biopsy samples<br>* Esophageal mucosal biopsies are collected during gastroscopy<br>Other: Blood samples<br>* Blood will be drawn by venipuncture into citrate- or ethylenediaminetetraacetic acid (EDTA)-containing vacutainer tubes and into serum tubes<br>|
| Control group<br>Individuals with no esophageal disease | Other: Biopsy samples<br>* Esophageal mucosal biopsies are collected during gastroscopy<br>Other: Blood samples<br>* Blood will be drawn by venipuncture into citrate- or ethylenediaminetetraacetic acid (EDTA)-containing vacutainer tubes and into serum tubes<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Analysis of cannabinoid receptors- protein content | Cannabinoid receptors (protein) are measured by flow cytometry in blood leukocytes of patients with EoE (acute and in remission), and of control individuals. | within 48 months | 
| Analysis of cannabinoid receptors- transcripts | Transcripts of cannabinoid receptors are measured in esophageal mucosal biopsies of patients with EoE (acute and in remission), GERD and in control individuals by polymerase chain reaction. | within 48 months | 
| Analysis of prostaglandin D2 receptors- protein content | Prostaglandin D2 receptors (protein) are measured by flow cytometry in blood leukocytes of patients with EoE (acute and in remission), and of control individuals. | within 48 months | 
| Analysis of prostaglandin D2 receptors - transcripts | Transcripts of prostaglandin D2 receptors are measured in esophageal mucosal biopsies of patients with EoE (acute and in remission), GERD and in control individuals by polymerase chain reaction. | within 48 months | 
| Analysis of prostaglandin E2 receptors- protein content | Prostaglandin E2 receptors (protein) are measured by flow cytometry in blood leukocytes of patients with EoE (acute and in remission), and of control individuals. | within 48 months | 
| Analysis of prostaglandin E2 receptors- transcripts | Transcripts of prostaglandin E2 receptors are measured in esophageal mucosal biopsies of patients with EoE (acute and in remission), GERD and in control individuals by polymerase chain reaction. | within 48 months | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Disease activity Score | Assessment of a Disease Activity Score: The Disease Activity Score will be assessed on the basis of the Gastroesophageal Reflux Disease-Health Related Quality of Life (GERD-HRQL) instrument (Dis Esophagus. 2007;20 (2):130-4) and consists of a questionnaire rated from 0 to 5 where 0 indicates no symptoms while 5 indicates strong symptoms of heartburn and difficulties in swallowing that incapacitates to do daily activities. | within 48 months | 
| Endoscopic Reference Score | Assessment of an Endoscopic Reference Score: Endoscopic findings will be assessed using the EoE Endoscopic Reference Score (EREFS) (Hirano et al. Gut. 2013; 62:489-495) which is composed of 5 classification categories. The classification features include edema, fixed rings, exsudates, furrows and stricture where grade 0 indicates the absence of the feature and grade 2 and 3 increasing severity of the feature. | within 48 months |