Local Clinical and Immunological Responses in Eosinophilic Esophagitis (EoE) Patients, Role of Mucosal Barrier Function and Type II Inflammation (SINFONIA)

Eosinophilic esophagitis (EoE) is an allergic inflammation of the esophagus. If not treated properly, inflammation and narrowing of the esophagus can occur. This can eventually lead to food impaction. Food allergens play an important role in the pathogenesis of EoE, as demonstrated by endoscopic and clinical resolution of EoE once the causative food is removed from the diet and exacerbation when the same food is reintroduced Similarly, amino acid-based

elemental diets are effective in both adults and children with EoE. However, the exact mechanism by which food allergens can initiate inflammation in EoE is still unknown, as there are limited data on the early local esophageal immune response after challenge with a specific food trigger. Previous research has shown that this can be treated with antacids (PPI) and corticosteroids. This reduces the permeability of the esophagus (which is increased in EoE), but not to the level of healthy individuals. Most likely this is due to a mild underlying allergic inflammation that persists under treatment with the above agents. The idea is that dupilumab inhibits this type II inflammation, which will further reduce the permeability. In addition, the effect of food allergens on esophageal biopsies from both EoE patients and healthy patients will be examined. This will then be compared to the biopsies taken after the use of dupilumab.

Study Overview

• Status: Recruiting
• Conditions: Eosinophilic Esophagitis (EoE)

• Study Type: Observational
• Enrollment (Estimated): 56

Contacts and Locations

• Study Contact: Name: Mandy Fijnenberg, WO medicine; Phone Number: +316 55946709; Email: m.fijnenberg@amsterdamumc.nl
• Study Contact Backup: Name: Albert J. Bredenoord, gastroenterologist; Email: a.j.bredenoord@amsterdamumc.nl

Study Locations

• Netherlands
  • Noord-holland
    • Amsterdam, Noord-holland, Netherlands, 1081HV
      • Recruiting
      • Amsterdam UMC
      • Contact: Mandy Fijnenberg; Phone Number: +316 55946709; Email: m.fijnenberg@amsterdamumc.nl
      • Contact: Albert J. Bredenoord; Email: a.j.bredenoord@amsterdamumc.nl
      • Sub-Investigator: Mandy Fijnenberg
      • Principal Investigator: Arjan Bredenoord

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Adult; Older Adult
• Accepts Healthy Volunteers: Yes

• Sampling Method: Non-Probability Sample

Study Population

Most of the patients will have active EoE at the beginning, 12 will be treated with dupilumab, 20 active disease patients. There will be 12 patients without EoE

Description

Inclusion Criteria:

EoE patient group with dupilumab or topical budesonide Previous diagnosis of active EoE confirmed by histopathology e.g. presence of 15 or more eosinophilic granulocytes per hpf in mid or proximal esophageal biopsies Scheduled to start with dupilumab or topical budesonide as regular care 18 to 75 years of age Written informed consent must be obtained and documented

EoE patient group with active EoE Previous diagnosis of active EoE confirmed by histopathology e.g. presence of 15 or more eosinophilic granulocytes per hpf in mid or proximal esophageal biopsies Scheduled for an upper endoscopy 18 to 75 years of age Written informed consent must be obtained and documented

Non-EoE control group Scheduled for a upper endoscopy for other, non-esophageal related, symptoms 18 to 75 years of age Written informed consent must be obtained and documented

Exclusion Criteria:

EoE patient group with dupilumab, topical budesonide and with active EoE Use of oral or systemic antihistaminics, oral cromoglicates, systemic corticosteroids, leukotriene inhibitors or monoclonal antibodies, in the month preceding the study Proven gastroesophageal reflux disease or other cause for esophageal eosinophilia, History of peptic ulcer disease, History of Barrett's esophagus, History of gastro intestinal cancer or ASA class III, IV or V

Non-EoE control group Symptoms suggestive of esophageal disease or other disease that may infolve the esophagus Personal history of atopic, skin or systemic diseases

Study Plan

How is the study designed?

Number of groups / cohorts

3

Cohorts and Interventions

Group / Cohort
Dupilumab; Blood, biopsies, questionnaire
Active EoE disease; Blood, biopsies, questionnaire
Control; Blood, biopsies

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Local clinical and immunological responses in eosinophilic esophagitis (EoE) patients, role of mucosal barrier function and type II inflammation	Esophagael barrier function improvement after 26 week of dupilumab treatment in EoE patients, assessed by the change in transepithelial electrical resistance (TEER).	26 weeks after dupilumab

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Food-induced immune responses in EoE patients after dupilumab	food-induced immune responses in esophageal biopsy specimens exposed to different food allergens ex vivo after dupilumab.	26 weeks after dupilumab

Collaborators and Investigators

• Sponsor: Academisch Medisch Centrum - Universiteit van Amsterdam (AMC-UvA)

Study record dates

Study Major Dates

• Study Start (Estimated): July 1, 2025
• Primary Completion (Estimated): June 30, 2027
• Study Completion (Estimated): May 31, 2028

Study Registration Dates

• First Submitted: May 15, 2025
• First Submitted That Met QC Criteria: June 5, 2025
• First Posted (Actual): June 10, 2025

Study Record Updates

• Last Update Posted (Actual): June 10, 2025
• Last Update Submitted That Met QC Criteria: June 5, 2025
• Last Verified: May 1, 2025

More Information

Terms related to this study

• Keywords: Eosinophilic Esophagitis; Dupilumab; TEER; Permeability esophagus
• Additional Relevant MeSH Terms: Pathologic Processes; Immune System Diseases; Digestive System Diseases; Gastrointestinal Diseases; Hypersensitivity, Immediate; Hypersensitivity; Eosinophilia; Leukocyte Disorders; Hematologic Diseases; Esophageal Diseases; Gastroenteritis; Inflammation; Esophagitis; Eosinophilic Esophagitis
• Other Study ID Numbers: 2024.0849; Sanofi (Other Grant/Funding Number: Sanofi Pathways in Type 2 Inflammation Global Innovation Grant)

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: UNDECIDED
• IPD Plan Description: Depends on the results

Drug and device information, study documents

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