Development, Validation and Evaluation of an Adult and Pediatric Eosinophilic Esophagitis Activity Index (EEsAI)

September 15, 2015 updated by: University Hospital Inselspital, Berne

Development, Validation and Evaluation of an Adult and Pediatric Eosinophilic Esophagitis Activity Index: A Prospective Multicenter Study

Eosinophilic Esophagitis (EoE) is a chronic inflammatory disease of the esophagus affecting children and adults. The most frequent symptoms are swallowing difficulties and thoracic pain. The disease has first been described in the 1980s and is found with rapidly increasing frequency mainly in industrialized countries. The factors that lead to EoE are until now incompletely understood, of importance, the disease is found more frequently in men and patients suffering from allergic diseases (e.g., Asthma). So far there exists no activity index to define the severity of EoE; such an index is urgently needed for future clinical trials to determine the efficacy of current and future therapies. The investigators' 3-year project, carried out in cooperation with international EoE experts, aims at the development of an activity index for adult and pediatric EoE patients that will be used in future clinical trials as well as observational studies.

Study Overview

Status

Unknown

Conditions

Intervention / Treatment

Detailed Description

Background:

1. Introduction Coordinated by the Swiss Eosinophilic Esophagitis Research Group and in close collaboration with The International Gastrointestinal Eosinophil Researchers (TIGERS), we plan to conduct a series of related studies in order to develop an Activity Index (AI) for adult and pediatric patients with Eosinophilic Esophagitis (EoE).

EoE is an emerging disease, with rapidly growing clinical relevance and research activities. A validated assessment instrument is therefore urgently needed.

The purpose of this project is to develop within a representative group of pediatric and adult EoE-experienced gastroenterologists and EoE-experienced pathologists an AI for this chronic inflammatory esophageal disease. The project is investigator initiated, but funding from different sources will be necessary. The project will be conducted in compliance with this protocol, with the ICH guideline E6 on Good Clinical Practice, the FDA perspectives on patient-reported outcomes to support medical product labeling claims (1,2), and the applicable regulatory requirements.

As EoE is a new disorder we include below a comprehensive description of the disease.

1.1. Characterization of Eosinophilic Esophagitis Definition: EoE is rapidly emerging as a distinctive disorder in pediatric and adult gastroenterology. EoE is a chronic-inflammatory esophageal disease, characterized clinicopathologically by the presence of esophagus-related symptoms and by a dense esophageal eosinophilia, both of which persist despite prolonged treatment with proton pump inhibitors (3). Epidemiology: EoE is diagnosed 2-3 times more frequently in males than in females.

The disease is found mainly in industrialized countries such as the United States, Canada, Europe and Australia. EoE is likely to be a 'young' disease: it had not been seen prior to the early 1980, and there is strong evidence to suggest that its prevalence is increasing (4)(5). A population-based study performed in Switzerland suggested an increase in prevalence from 2 per 100000 to 40 per 100000 inhabitants over a 19-year period (6). Clinical Symptoms: As in many other diseases, symptom presentation differs significantly between children and adults. In infants and toddlers, food refusal is a common symptom of EoE. Children often suffer from GERD-like symptoms, vomiting and abdominal pain. Dysphagia and food impaction are reported increasingly with proceeding age. Adolescents and adults present mostly with dysphagia for solids and food impaction (5-7). Endoscopy/Histology: Esophago-gastro-duodenoscopy (EGD) is the first diagnostic step in the evaluation of an individual with suspected EoE. A broad spectrum of endoscopic features associated with EoE have been described, but the endoscopic suspicion needs confirmation by histology. The key diagnostic criterion for diagnosing EoE is an increased number of intraepithelial eosinophils in patients with lack of responsiveness to high-dose proton pump inhibition or normal pH-monitoring of the distal esophagus. In a consensus conference a cut-off value of =15 Eos/HPF (peak eosinophilic count in 400 fold magnification) in any biopsy was recommended as diagnostic criterion (3). Treatment: The optimal treatment for EoE is not yet clear, as experience has been limited largely to case series and small controlled trials. So far topically and systemically administered corticosteroids, several types of allergen-reduced diets, immunosuppressants and IL-5 blocking agents have been shown to be efficacious (8-11).

1.2. Rationale for the planned Studies In the clinical setting the current status of a given disease is often reported as "mild", "moderate" and "severe", and the course of the disease over time is described with terms such as "stable", "progressive", "in remission" or "flare-up". None of these terms has so far been clearly defined for EoE. However, an increasing number of phase 3 therapeutic multi-center trials and natural history studies in patients with EoE will be performed in the near future. In order to set up standardized study protocols and to compare results between different studies a standardized definition of disease activity is a necessity. Taken together, for clinical and for research purposes it is indispensable to define the terms mentioned above by a suitable, reproducible and validated score, which reflects the disease activity as precisely as possible. The necessity for such a score has repeatedly been discussed by the TIGERS and has been underscored by several publications (12).

Objective

The planned research program has the aim to develop and validate an AI for EoE (EEsAI) for adult (adEEsAI) and pediatric (pedEEsAI) patients, which can be used in future clinical trials and observational studies. According to the characterization of EoE, the AI will likely contain clinical and histopathological items. Laboratory and endoscopical parameters may be part of the score, but in a subsidiary role.

Methods:

The development and validation of a disease activity index is a research program involving several related studies. Broadly speaking, it involves 3 main steps: Step I Item Generation and Reduction through a Delphi process with an international expert group (Development phase A). Step II Item Weighting and Activity Index Derivation, using data from a first cohort of adult and a first cohort of pediatric patients (Development phase B).

Step III Evaluation of the Activity Index using data from a second independent cohort of adult and pediatric patients respectively. This involves also assessment of test-retest reliability and responsiveness of the score, using longitudinal data from the same patients.

Study Type

Observational

Enrollment (Anticipated)

650

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Contact

Study Contact Backup

Study Locations

  • Canada
    • Ontario
      • Hamilton, Ontario, Canada
        • Not yet recruiting
        • Clinical Epidemiology & Biostatistics : Mc Master University
        • Principal Investigator:
          • Paul Moayyedi, MD PhD
    • Quebec
      • Montréal, Quebec, Canada
        • Not yet recruiting
        • Ste-Justine Hospital : University of Montreal
        • Principal Investigator:
          • Éric Drouin, MD
  • Switzerland
      • Bern, Switzerland, 3010
        • Withdrawn
        • Department of Gastroenterology, Inselspital/Bern University Hospital
      • Bern, Switzerland, 3010
        • Not yet recruiting
        • Pädiatrische Gastroenterologie Medizinische Universitäts-Kinderklinik Bern
        • Principal Investigator:
          • Susanne Schibli, MD
      • Bern, Switzerland, 3012
        • Recruiting
        • Institute for Social and Preventive Medicine, University of Bern
        • Contact:
        • Contact:
        • Principal Investigator:
          • Marcel Zwahlen, PhD, Prof.
        • Principal Investigator:
          • Claudia Kuehni, MD MSc, Prof.
        • Sub-Investigator:
          • Ekaterina Safroneeva, PhD
      • Lausanne, Switzerland, 1011
        • Recruiting
        • University Hospital Lausanne (CHUV)
        • Principal Investigator:
          • Alain Schoepfer, MD, PD+MER1
      • Lucerne, Switzerland, 6000
        • Recruiting
        • Department of Gastroenterology and Hepatology, Kantonsspital Lucerne
        • Principal Investigator:
          • Dominique Criblez
      • Lucerne, Switzerland, 6000
        • Not yet recruiting
        • Institute for Pathology, Kantonsspital Lucerne
        • Principal Investigator:
          • Christian Bussmann, MD
      • Olten, Switzerland, 4600
        • Recruiting
        • Praxis Römerhof, Römerstr. 7, Olten
        • Principal Investigator:
          • Alex Straumann, MD, Prof.
      • St. Gallen, Switzerland, 9006
        • Not yet recruiting
        • Ostschweizer Kinderspital
        • Principal Investigator:
          • Pascal Mueller, MD
  • United Kingdom
      • North Shields, United Kingdom
        • Withdrawn
        • Northumbria Healthcare Foundation Trust North Tyneside Hospital
  • United States
    • Arizona
      • Scottsdale, Arizona, United States, 85261
        • Recruiting
        • Gastroenterology and Hepatology : Mayo Clinic, Scottsdale
        • Principal Investigator:
          • Pasha Fatima Shabana, MD
    • California
      • San Diego, California, United States, 92123
        • Recruiting
        • Department of Pediatrics : University of California
        • Principal Investigator:
          • Seema Aceves, MD PhD
    • Colorado
      • Aurora, Colorado, United States, 80045
        • Recruiting
        • The Children's Hospital : University of Colorado Denver
        • Principal Investigator:
          • Glenn Furuta, MD
    • Florida
      • Jacksonville, Florida, United States, 32224
        • Recruiting
        • Gastroenterology and Hepatology : Mayo Clinic, Jacksonville
        • Principal Investigator:
          • Sami R Achem, MD
    • Illinois
      • Chicago, Illinois, United States, 60611
        • Recruiting
        • Division of Gastroenterology : Northwestern University Chicago
        • Principal Investigator:
          • Ikuo Hirano, MD
      • Chicago, Illinois, United States, 60614
        • Recruiting
        • Gastroenterology, hepatology and nutrition : Ann & Robert H. Lurie Children's Hospital of Chicago
        • Principal Investigator:
          • Amir Kagalwalla, MD
    • Indiana
      • Indianapolis, Indiana, United States, 46202
        • Recruiting
        • Riley Hospital for Children : Indiana University School of Medicine
        • Principal Investigator:
          • Sandeep Gupta, MD
    • Massachusetts
      • Boston, Massachusetts, United States, 02112
        • Recruiting
        • Institute for Clinical Research and Health Policy Studies: Tufts Medical Center
      • Brookline, Massachusetts, United States, 02112
        • Not yet recruiting
        • Division of Allergy and Inflammation : Harvard Medical School Boston
        • Principal Investigator:
          • Javed Sheikh, MD
    • Minnesota
      • Rochester, Minnesota, United States
        • Recruiting
        • Mayo Clinic Rochester
        • Principal Investigator:
          • Yvonne Romero, MD
        • Sub-Investigator:
          • Jeffrey Alexander, MD
        • Sub-Investigator:
          • Rayna Grothe, MD
    • New York
      • New York, New York, United States, 10029
        • Recruiting
        • Pediatrics : Mount Sinai School of Medicine
        • Principal Investigator:
          • Mirna Chehade, MD MPH
    • Ohio
      • Cincinnati, Ohio, United States, 45229
        • Withdrawn
        • Gastroenterology, Hepatology and Nutrition : University of Cincinnati
    • Pennsylvania
      • Philadelphia, Pennsylvania, United States, 19104
        • Recruiting
        • Children's Hospital of Philadelphia : University of Philadelphia
        • Principal Investigator:
          • Jonathan Spergel, MD, PhD
    • Virginia
      • Fairfax, Virginia, United States
        • Not yet recruiting
        • Inova Fairfax Hospital for Children
        • Principal Investigator:
          • Benjamin Enav, MD
        • Sub-Investigator:
          • Oral Alpan, MD

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

  • Child
  • Adult
  • Older Adult

Accepts Healthy Volunteers

No

Genders Eligible for Study

All

Sampling Method

Non-Probability Sample

Study Population

Adult and pediatric patients with the diagnosis Eosinophilic Esophagitis, who are treated in the participating hospitals

Description

Inclusion Criteria:

  • every patient with the diagnosis Eosinophilic Esophagitis
  • pediatric and adult EoE patients

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Observational Models: Cohort
  • Time Perspectives: Prospective

Cohorts and Interventions

Group / Cohort
Intervention / Treatment
1
cohorts 1 (item weighting phase): 100 children with Eosinophilic Esophagitis, 150 adults with Eosinophilic Esophagitis
Other: assessment of disease activity using the EEsAI
disease activity index
2
cohorts 2 (evaluation phase): 200 children with Eosinophilic Esophagitis, 200 adults with Eosinophilic Esophagitis
Other: assessment of disease activity using the EEsAI
disease activity index

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Time Frame
Development of an EE Activity Index
Time Frame: 12 months
12 months

Secondary Outcome Measures

Outcome Measure
Time Frame
Evaluation and validation of the activity index
Time Frame: 2 years
2 years

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

University Hospital Inselspital, Berne

Collaborators

University of Colorado, Denver
Mayo Clinic
Northwestern University
University of Cincinnati
University of Bern
Luzerner Kantonsspital
Indiana University School of Medicine
Kantonsspital Olten
Philadelphia University

Investigators

  • Principal Investigator: Alain Schoepfer, MD, PD+MER1, Department of Gastroenterology and Hepatology, Centre Hospitalier Universitaire Vaudois / CHUV
  • Study Chair: Alex Straumann, MD, Prof., Praxis Römerhof, Olten, Switzerland
  • Study Director: Marcel Zwahlen, PhD, Prof., Institute for Social and Preventive Medicine, University of Bern
  • Study Director: Claudia Kuehni, MD MSc, Prof., Institute for Social and Preventive Medicine, University of Bern
  • Study Director: Christian Bussmann, MD, Viollier AG

Publications and helpful links

The person responsible for entering information about the study voluntarily provides these publications. These may be about anything related to the study.

General Publications

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start

January 1, 2011

Primary Completion (Anticipated)

July 1, 2016

Study Completion (Anticipated)

December 1, 2016

Study Registration Dates

First Submitted

July 13, 2009

First Submitted That Met QC Criteria

July 13, 2009

First Posted (Estimate)

July 14, 2009

Study Record Updates

Last Update Posted (Estimate)

September 16, 2015

Last Update Submitted That Met QC Criteria

September 15, 2015

Last Verified

September 1, 2015

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

  • 231/08
  • 0901 (Ethikkommision KiKli BE)

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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