Prostaglandin and Cannabinoid Receptors in EoE

Prostaglandin and Cannabinoid Receptors in the Development of Eosinophilic Esophagitis

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.

Study Overview

• Status: Recruiting
• Conditions: Eosinophilic Esophagitis (EoE)
• Intervention / Treatment: Other: Biopsy samples; Other: Blood samples

Detailed Description

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.

• Study Type: Observational
• Enrollment (Anticipated): 60

Contacts and Locations

• Study Contact: Name: Rudolf Schicho, PhD; Phone Number: 74132 +43316385; Email: rudolf.schicho@medunigraz.at
• Study Contact Backup: Name: Franziska Durchschein, MD; Email: franziska.durchschein@medunigraz.at

Study Locations

• Austria
  • Graz, Austria, 8036
    • Recruiting
    • Medical University of Graz
    • Contact: Durchschein Franziska, MD

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: Yes
• Genders Eligible for Study: All

• Sampling Method: Non-Probability Sample

Study Population

Subjects undergoing gastroscopy at the outpatients clinic of the Medical University of Graz

Description

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

Study Plan

How is the study designed?

Design Details

• Observational Models: Cohort
• Time Perspectives: Prospective

Number of groups / cohorts

3

Cohorts and Interventions

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

What is the study measuring?

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
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
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

Collaborators and Investigators

• Sponsor: Medical University of Graz
• Investigators: Principal Investigator: Rudolf Schicho, PhD, Medical University of Graz

Study record dates

Study Major Dates

• Study Start (Actual): July 1, 2021
• Primary Completion (Anticipated): February 1, 2025
• Study Completion (Anticipated): February 1, 2025

Study Registration Dates

• First Submitted: November 6, 2020
• First Submitted That Met QC Criteria: November 6, 2020
• First Posted (Actual): November 12, 2020

Study Record Updates

• Last Update Posted (Actual): March 20, 2023
• Last Update Submitted That Met QC Criteria: March 16, 2023
• Last Verified: March 1, 2023

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Digestive System Diseases; Immune System Diseases; Hypersensitivity, Immediate; Hematologic Diseases; Gastrointestinal Diseases; Gastroenteritis; Hypersensitivity; Esophageal Diseases; Leukocyte Disorders; Eosinophilia; Eosinophilic Esophagitis; Esophagitis
• Other Study ID Numbers: KLI 887-B

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No