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AzTrials

Deglutition DisordersEEsAINCT00939263

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

An observational study of Deglutition Disorders and Esophageal Diseases, run by Insel Gruppe AG, University Hospital Bern at 25 sites in 4 countries.

Unknown status

Status not confirmed. The sponsor has not verified this record for over two years, so it may be out of date.

Official record
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Trial 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. Read more about this study

Who is it for?
Any age
What is being tested?
assessment of disease activity using the EEsAI
How many people
650 participants
Where
25 sitesin 4 countries
Study dates
Jan 2011to Dec 2016
Phase
Observational
Are there results?
None posted in the registry

Key requirements

Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.

  • Ages Any age
  • All sexes
  • No healthy volunteers
  • Child, Adult, Older adult

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

Who may be able to join

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

Who cannot join

None listed.

Trial locations and contacts

25 sites in 4 countries.

Ekaterina Safroneeva, PhD contact

+41 31 631 59 71

esafroneeva@ispm.unibe.ch

Claudia Kuehni, MD MSc, Prof. contact

+41 31 631 35 07

kuehni@ispm.unibe.ch

25 sites in 4 countries

United States14 sites, 13 recruiting
  • The Children's Hospital : University of Colorado Denver

    Aurora, Colorado, 80045

    Glenn Furuta, MD

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

    Boston, Massachusetts, 02112

    John Leung, MD

    Recruiting
  • Division of Allergy and Inflammation : Harvard Medical School Boston

    Brookline, Massachusetts, 02112

    Javed Sheikh, MD

    Not yet recruiting
  • Division of Gastroenterology : Northwestern University Chicago

    Chicago, Illinois, 60611

    Ikuo Hirano, MD

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

    Chicago, Illinois, 60614

    Amir Kagalwalla, MD

    Recruiting
  • Gastroenterology, Hepatology and Nutrition : University of Cincinnati

    Cincinnati, Ohio, 45229

    Withdrawn
  • Inova Fairfax Hospital for Children

    Fairfax, Virginia

    Benjamin Enav, MD

    Oral Alpan, MD

    Not yet recruiting
  • Riley Hospital for Children : Indiana University School of Medicine

    Indianapolis, Indiana, 46202

    Sandeep Gupta, MD

    Recruiting
  • Gastroenterology and Hepatology : Mayo Clinic, Jacksonville

    Jacksonville, Florida, 32224

    Sami R Achem, MD

    Recruiting
  • Pediatrics : Mount Sinai School of Medicine

    New York, New York, 10029

    Mirna Chehade, MD MPH

    Recruiting
  • Children's Hospital of Philadelphia : University of Philadelphia

    Philadelphia, Pennsylvania, 19104

    Jonathan Spergel, MD, PhD

    Recruiting
  • Mayo Clinic Rochester

    Rochester, Minnesota

    Yvonne Romero, MD

    Jeffrey Alexander, MD

    Recruiting
  • Department of Pediatrics : University of California

    San Diego, California, 92123

    Seema Aceves, MD PhD

    Recruiting
  • Gastroenterology and Hepatology : Mayo Clinic, Scottsdale

    Scottsdale, Arizona, 85261

    Pasha Fatima Shabana, MD

    Recruiting

Other trials in United States

Switzerland8 sites, 7 recruiting
  • Department of Gastroenterology, Inselspital/Bern University Hospital

    Bern, 3010

    Withdrawn
  • Pädiatrische Gastroenterologie Medizinische Universitäts-Kinderklinik Bern

    Bern, 3010

    Susanne Schibli, MD

    Not yet recruiting
  • Institute for Social and Preventive Medicine, University of Bern

    Bern, 3012

    Ekaterina Safroneeva, PhD, +41 31 631 59 71, esafroneeva@ispm.unibe.ch

    Claudia Kuehni, MD MSc, Prof., +41 31 631 35 07, kuehni@ispm.unibe.ch

    Recruiting
  • University Hospital Lausanne (CHUV)

    Lausanne, 1011

    Alain Schoepfer, MD, PD+MER1

    Recruiting
  • Department of Gastroenterology and Hepatology, Kantonsspital Lucerne

    Lucerne, 6000

    Dominique Criblez

    Recruiting
  • Institute for Pathology, Kantonsspital Lucerne

    Lucerne, 6000

    Christian Bussmann, MD

    Not yet recruiting
  • Praxis Römerhof, Römerstr. 7, Olten

    Olten, 4600

    Alex Straumann, MD, Prof.

    Recruiting
  • Ostschweizer Kinderspital

    Sankt Gallen, 9006

    Pascal Mueller, MD

    Not yet recruiting

Other trials in Switzerland

Canada2 sites, 2 recruiting
  • Clinical Epidemiology & Biostatistics : Mc Master University

    Hamilton, Ontario

    Paul Moayyedi, MD PhD

    Not yet recruiting
  • Ste-Justine Hospital : University of Montreal

    Montreal, Quebec

    Éric Drouin, MD

    Not yet recruiting

Other trials in Canada

United Kingdom1 site
  • Northumbria Healthcare Foundation Trust North Tyneside Hospital

    North Shields

    Withdrawn

Other trials in United Kingdom

About this study

Official title: 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.

Read the 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.

Being tested
assessment of disease activity using the EEsAI
Keywords
deglutition disorders, esophageal diseases, eosinophilia
Medical subject headings
Deglutition Disorders, Esophageal Diseases, Eosinophilia

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

  • assessment of disease activity using the EEsAIOther

    disease activity index

Study groups in NCT00939263
Study groupRoleWhat they receive
1cohorts 1 (item weighting phase): 100 children with Eosinophilic Esophagitis, 150 adults with Eosinophilic Esophagitis
Receives: Other: assessment of disease activity using the EEsAI
2cohorts 2 (evaluation phase): 200 children with Eosinophilic Esophagitis, 200 adults with Eosinophilic Esophagitis
Receives: Other: assessment of disease activity using the EEsAI

What is being measured

The primary outcome is the main question the study is designed to answer.

  1. Development of an EE Activity Index

    Measured: 12 months

Secondary outcomes (1)
  1. Evaluation and validation of the activity index

    Measured: 2 years

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

  1. First posted14 Jul 2009 (estimated)
  2. Study startJan 2011
  3. Primary completionJul 2016 (estimated)
  4. Study completionDec 2016 (estimated)

Resources

More details

For doctors and researchers: how the study is designed, who runs it, and its registry IDs.

Study design
Study type
Observational
Observational model
Cohort
Time perspective
Prospective
Enrolment
650 participants (estimated)
IDs, dates and publications
ClinicalTrials.gov ID
NCT00939263
Sponsor's protocol ID
231/08
Other IDs
0901
Acronym
EEsAI
Status last verified
Sep 2015
First submitted
13 Jul 2009
Last updated
16 Sep 2015
Results posted
No
Data monitoring committee
Yes

Publications

  • 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.

    PubMed 17034633
  • 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.

    PubMed 17995471
  • 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.

    PubMed 17919504
  • 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.

    PubMed 15696105
  • Noel RJ, Putnam PE, Rothenberg ME. Eosinophilic esophagitis. N Engl J Med. 2004 Aug 26;351(9):940-1. doi: 10.1056/NEJM200408263510924. No abstract available.

    PubMed 15329438
  • Straumann A, Spichtin HP, Grize L, Bucher KA, Beglinger C, Simon HU. Natural history of primary eosinophilic esophagitis: a follow-up of 30 adult patients for up to 11.5 years. Gastroenterology. 2003 Dec;125(6):1660-9. doi: 10.1053/j.gastro.2003.09.024.

    PubMed 14724818
  • Liacouras CA, Spergel JM, Ruchelli E, Verma R, Mascarenhas M, Semeao E, Flick J, Kelly J, Brown-Whitehorn T, Mamula P, Markowitz JE. Eosinophilic esophagitis: a 10-year experience in 381 children. Clin Gastroenterol Hepatol. 2005 Dec;3(12):1198-206. doi: 10.1016/s1542-3565(05)00885-2.

    PubMed 16361045
  • 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.

    PubMed 2659745
  • 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.

    PubMed 30476587
  • Safroneeva E, Straumann A, Coslovsky M, Zwahlen M, Kuehni CE, Panczak R, Haas NA, Alexander JA, Dellon ES, Gonsalves N, Hirano I, Leung J, Bussmann C, Collins MH, Newbury RO, De Petris G, Smyrk TC, Woosley JT, Yan P, Yang GY, Romero Y, Katzka DA, Furuta GT, Gupta SK, Aceves SS, Chehade M, Spergel JM, Schoepfer AM; International Eosinophilic Esophagitis Activity Index Study Group. Symptoms Have Modest Accuracy in Detecting Endoscopic and Histologic Remission in Adults With Eosinophilic Esophagitis. Gastroenterology. 2016 Mar;150(3):581-590.e4. doi: 10.1053/j.gastro.2015.11.004. Epub 2015 Nov 14.

    PubMed 26584601
  • Safroneeva E, Coslovsky M, Kuehni CE, Zwahlen M, Haas NA, Panczak R, Taft TH, Hirano I, Dellon ES, Gonsalves N, Leung J, Bussmann C, Woosley JT, Yan P, Romero Y, Furuta GT, Gupta SK, Aceves SS, Chehade M, Straumann A, Schoepfer AM; International EEsAI Study Group. Eosinophilic oesophagitis: relationship of quality of life with clinical, endoscopic and histological activity. Aliment Pharmacol Ther. 2015 Oct;42(8):1000-10. doi: 10.1111/apt.13370. Epub 2015 Aug 14.

    PubMed 26271642
  • Schoepfer AM, Straumann A, Panczak R, Coslovsky M, Kuehni CE, Maurer E, Haas NA, Romero Y, Hirano I, Alexander JA, Gonsalves N, Furuta GT, Dellon ES, Leung J, Collins MH, Bussmann C, Netzer P, Gupta SK, Aceves SS, Chehade M, Moawad FJ, Enders FT, Yost KJ, Taft TH, Kern E, Zwahlen M, Safroneeva E; International Eosinophilic Esophagitis Activity Index Study Group. Development and validation of a symptom-based activity index for adults with eosinophilic esophagitis. Gastroenterology. 2014 Dec;147(6):1255-66.e21. doi: 10.1053/j.gastro.2014.08.028. Epub 2014 Aug 23.

    PubMed 25160980

Questions about this trial

What is this clinical trial studying?

An observational study of Deglutition Disorders and Esophageal Diseases, run by Insel Gruppe AG, University Hospital Bern at 25 sites in 4 countries.

The full registered description is in the About this study section and the official record.

Who may be eligible to take part?

The sponsor lists 2 inclusion and 0 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.

Is this clinical trial currently recruiting?

The record says: status not confirmed, as of the sponsor's last update on 16 Sep 2015. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 25 sites in United States, Switzerland, Canada, United Kingdom. Whether a site is taking part right now should be confirmed with that site. See every site.

What are the possible benefits and risks?

They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.

Are results available for this study?

Results are not available in the source record.

How can a doctor refer a patient or contact the research team?

Contact Ekaterina Safroneeva, PhD (+41 31 631 59 71, esafroneeva@ispm.unibe.ch), or a site near the patient. AzTrials does not enrol participants or take referrals.

What does the primary outcome measure?

Development of an EE Activity Index (time frame: 12 months). It is what the study was designed to measure, not a finding.

Where can I read the original study information?

On the ClinicalTrials.gov record for NCT00939263, which also lists 12 linked publications.

Does a listing mean the treatment is approved or proven to work?

No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.

How often is this information updated?

AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 16 Sep 2015.

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