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

NCT ID: NCT00939263

Last Updated: 2015-09-16

Basic Information

• Recruitment Status: UNKNOWN
• Total Enrollment: 650 participants
• Study Classification: OBSERVATIONAL
• Study Start Date: 2011-01-31
• Study Completion Date: 2016-12-31

Brief Summary

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.

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.

Conditions

Deglutition Disorders; Esophageal Diseases; Eosinophilia

Study Design

• Observational Model Type: COHORT
• Study Time Perspective: PROSPECTIVE

Study Groups

1

cohorts 1 (item weighting phase): 100 children with Eosinophilic Esophagitis, 150 adults with Eosinophilic Esophagitis

assessment of disease activity using the EEsAI

Intervention Type: OTHER

disease activity index

2

cohorts 2 (evaluation phase): 200 children with Eosinophilic Esophagitis, 200 adults with Eosinophilic Esophagitis

assessment of disease activity using the EEsAI

Intervention Type: OTHER

disease activity index

Interventions

assessment of disease activity using the EEsAI

disease activity index

Intervention Type: OTHER

Eligibility Criteria

Inclusion Criteria

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

• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

University of Bern

OTHER

Sponsor Role: collaborator

Kantonsspital Olten

OTHER

Sponsor Role: collaborator

Luzerner Kantonsspital

OTHER

Sponsor Role: collaborator

Mayo Clinic

OTHER

Sponsor Role: collaborator

University of Cincinnati

OTHER

Sponsor Role: collaborator

University of Colorado, Denver

OTHER

Sponsor Role: collaborator

Northwestern University

OTHER

Sponsor Role: collaborator

Indiana University School of Medicine

OTHER

Sponsor Role: collaborator

Philadelphia University

OTHER

Sponsor Role: collaborator

Insel Gruppe AG, University Hospital Bern

OTHER

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

Alain Schoepfer, MD, PD+MER1

Role: PRINCIPAL_INVESTIGATOR

Department of Gastroenterology and Hepatology, Centre Hospitalier Universitaire Vaudois / CHUV

Alex Straumann, MD, Prof.

Role: STUDY_CHAIR

Praxis Römerhof, Olten, Switzerland

Marcel Zwahlen, PhD, Prof.

Role: STUDY_DIRECTOR

Institute for Social and Preventive Medicine, University of Bern

Claudia Kuehni, MD MSc, Prof.

Role: STUDY_DIRECTOR

Institute for Social and Preventive Medicine, University of Bern

Christian Bussmann, MD

Role: STUDY_DIRECTOR

Viollier AG

Locations

Gastroenterology and Hepatology : Mayo Clinic, Scottsdale

Scottsdale, Arizona, United States

Site Status: RECRUITING

Department of Pediatrics : University of California

San Diego, California, United States

Site Status: RECRUITING

The Children's Hospital : University of Colorado Denver

Aurora, Colorado, United States

Site Status: RECRUITING

Gastroenterology and Hepatology : Mayo Clinic, Jacksonville

Jacksonville, Florida, United States

Site Status: RECRUITING

Division of Gastroenterology : Northwestern University Chicago

Chicago, Illinois, United States

Site Status: RECRUITING

Gastroenterology, hepatology and nutrition : Ann & Robert H. Lurie Children's Hospital of Chicago

Chicago, Illinois, United States

Site Status: RECRUITING

Riley Hospital for Children : Indiana University School of Medicine

Indianapolis, Indiana, United States

Site Status: RECRUITING

Institute for Clinical Research and Health Policy Studies: Tufts Medical Center

Boston, Massachusetts, United States

Site Status: RECRUITING

Division of Allergy and Inflammation : Harvard Medical School Boston

Brookline, Massachusetts, United States

Site Status: NOT_YET_RECRUITING

Mayo Clinic Rochester

Rochester, Minnesota, United States

Site Status: RECRUITING

Pediatrics : Mount Sinai School of Medicine

New York, New York, United States

Site Status: RECRUITING

Gastroenterology, Hepatology and Nutrition : University of Cincinnati

Cincinnati, Ohio, United States

Site Status: WITHDRAWN

Children's Hospital of Philadelphia : University of Philadelphia

Philadelphia, Pennsylvania, United States

Site Status: RECRUITING

Inova Fairfax Hospital for Children

Fairfax, Virginia, United States

Site Status: NOT_YET_RECRUITING

Clinical Epidemiology & Biostatistics : Mc Master University

Hamilton, Ontario, Canada

Site Status: NOT_YET_RECRUITING

Ste-Justine Hospital : University of Montreal

Montreal, Quebec, Canada

Site Status: NOT_YET_RECRUITING

Department of Gastroenterology, Inselspital/Bern University Hospital

Bern, , Switzerland

Site Status: WITHDRAWN

Pädiatrische Gastroenterologie Medizinische Universitäts-Kinderklinik Bern

Bern, , Switzerland

Site Status: NOT_YET_RECRUITING

Institute for Social and Preventive Medicine, University of Bern

Bern, , Switzerland

Site Status: RECRUITING

University Hospital Lausanne (CHUV)

Lausanne, , Switzerland

Site Status: RECRUITING

Department of Gastroenterology and Hepatology, Kantonsspital Lucerne

Lucerne, , Switzerland

Site Status: RECRUITING

Institute for Pathology, Kantonsspital Lucerne

Lucerne, , Switzerland

Site Status: NOT_YET_RECRUITING

Praxis Römerhof, Römerstr. 7, Olten

Olten, , Switzerland

Site Status: RECRUITING

Ostschweizer Kinderspital

Sankt Gallen, , Switzerland

Site Status: NOT_YET_RECRUITING

Northumbria Healthcare Foundation Trust North Tyneside Hospital

North Shields, , United Kingdom

Site Status: WITHDRAWN

Countries

United States; Canada; Switzerland; United Kingdom

Central Contacts

Ekaterina Safroneeva, PhD

Role: CONTACT

esafroneeva@ispm.unibe.ch

+41 31 631 59 71

Claudia Kuehni, MD MSc, Prof.

Role: CONTACT

kuehni@ispm.unibe.ch

+41 31 631 35 07

Facility Contacts

Ekaterina Safroneeva, PhD

Role: primary

esafroneeva@ispm.unibe.ch

+41 31 631 59 71

Claudia Kuehni, MD MSc, Prof.

Role: backup

kuehni@ispm.unibe.ch

+41 31 631 35 07

References

U.S. Department of Health and Human Services FDA Center for Drug Evaluation and Research; U.S. Department of Health and Human Services FDA Center for Biologics Evaluation and Research; U.S. Department of Health and Human Services FDA Center for Devices and Radiological Health. Guidance for industry: patient-reported outcome measures: use in medical product development to support labeling claims: draft guidance. Health Qual Life Outcomes. 2006 Oct 11;4:79. doi: 10.1186/1477-7525-4-79.

Reference Type: BACKGROUND

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Patrick DL, Burke LB, Powers JH, Scott JA, Rock EP, Dawisha S, O'Neill R, Kennedy DL. Patient-reported outcomes to support medical product labeling claims: FDA perspective. Value Health. 2007 Nov-Dec;10 Suppl 2:S125-37. doi: 10.1111/j.1524-4733.2007.00275.x.

Reference Type: BACKGROUND

PMID: 17995471 (View on PubMed)

Furuta GT, Liacouras CA, Collins MH, Gupta SK, Justinich C, Putnam PE, Bonis P, Hassall E, Straumann A, Rothenberg ME; First International Gastrointestinal Eosinophil Research Symposium (FIGERS) Subcommittees. Eosinophilic esophagitis in children and adults: a systematic review and consensus recommendations for diagnosis and treatment. Gastroenterology. 2007 Oct;133(4):1342-63. doi: 10.1053/j.gastro.2007.08.017. Epub 2007 Aug 8.

Reference Type: BACKGROUND

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Straumann A, Simon HU. Eosinophilic esophagitis: escalating epidemiology? J Allergy Clin Immunol. 2005 Feb;115(2):418-9. doi: 10.1016/j.jaci.2004.11.006. No abstract available.

Reference Type: BACKGROUND

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Reference Type: BACKGROUND

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Guyatt GH, Deyo RA, Charlson M, Levine MN, Mitchell A. Responsiveness and validity in health status measurement: a clarification. J Clin Epidemiol. 1989;42(5):403-8. doi: 10.1016/0895-4356(89)90128-5.

Reference Type: BACKGROUND

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Schoepfer AM, Hirano I, Coslovsky M, Roumet MC, Zwahlen M, Kuehni CE, Hafner D, Alexander JA, Dellon ES, Gonsalves N, Leung J, Bussmann C, Collins MH, Newbury RO, Smyrk TC, Woosley JT, Yang GY, Romero Y, Katzka DA, Furuta GT, Gupta SK, Aceves SS, Chehade M, Spergel JM, Falk GW, Meltzer BA, Comer GM, Straumann A, Safroneeva E; International EEsAI Study Group. Variation in Endoscopic Activity Assessment and Endoscopy Score Validation in Adults With Eosinophilic Esophagitis. Clin Gastroenterol Hepatol. 2019 Jul;17(8):1477-1488.e10. doi: 10.1016/j.cgh.2018.11.032. Epub 2018 Nov 23.

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Reference Type: DERIVED

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Reference Type: DERIVED

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Other Identifiers

0901

Identifier Type: OTHER

Identifier Source: secondary_id

231/08

Identifier Type: -

Identifier Source: org_study_id