Clinical trial NCT02008903: Esophageal String Test in Eosinophilic Esophagitis
Official title: Phase 2 Study of Esophageal String Test in Diagnosing Eosinophilic Esophagitis
Study type: OBSERVATIONAL
Overall status: ACTIVE_NOT_RECRUITING
Conditions: Eosinophilic Esophagitis
Lead sponsor: University of Colorado, Denver
Sponsor class: OTHER
Collaborators: name: University of Illinois at Chicago
name: Northwestern University
name: OSF Healthcare System
First posted: 2013-12-11
Enrollment: 440
Sex: ALL
Minimum age (years): 7
Maximum age (years): 65
Standard ages: CHILD
ADULT
OLDER_ADULT
Accepts healthy volunteers: yes
Observational model: OTHER
Time perspective: PROSPECTIVE
Sampling method: NON_PROBABILITY_SAMPLE
Study population: Any pediatric or adult patient undergoing a clinically indicated endoscopy with biopsy at a participating site may be recruited. (initial cohort)

Brief summary: The overall goal of this study is to develop a novel minimally invasive device, the Esophageal String Test (EST) to monitor esophageal inflammation during treatment of the rare disease Eosinophilic Esophagitis (EoE) in a safe and efficacious manner.

This study is broken down into 2 specific aims:

Specific Aim 1: Identify the EoE Biomarker Panel (EBP) that will improve the sensitivity and specificity of the EST for documenting esophageal inflammation in a 1-hour time point.

Specific Aim 2: Validate the ability of the EST EBP to monitor therapeutic efficacy in a 1-hour sampling time.

Funding Source - FDA OOPD

Detailed description: Eosinophilic esophagitis (EoE) is an increasingly recognized rare disease of children and adults characterized by symptoms including nausea, vomiting, abdominal pain, dysphagia and food impaction that occur in conjunction with esophageal eosinophilia. To date, the only method to make EoE diagnoses and follow treatment responses in EoE is invasive endoscopy with biopsy. While endoscopy is generally safe, an accurate, less invasive, inexpensive, comprehensive and durable test is urgently needed to determine therapeutic efficacy. To address this need, the investigators will use a novel application of an existing technology, the Enterotest™ (a string-based test used to detect intestinal Giardiasis), to measure esophageal inflammation (herein termed the Esophageal String Test - EST). The investigators supportive Preliminary Data provide proof-of-principle for the ability of ESTs to capture esophageal inflammatory mediators in luminal samples from patients affected with EoE. The investigators prospective study demonstrates that: (1) levels of eosinophil-derived granule proteins (MBP1, EDN, ECP, EPX, CLC/Gal-10) in esophageal mucosal biopsies correlate with levels quantitated in EST-captured samples, i.e., levels in luminal secretions captured by the EST correlate with mucosal inflammation, and (2) these luminal biomarkers of eosinophilic inflammation significantly correlate with EoE disease activity. These findings provide strong support for using ESTs as novel minimally invasive instruments to monitor therapeutic efficacy in EoE. The global objective of this project is therefore to bring the "Esophageal String Test" (EST) to commercialization, so that it can be used to monitor therapeutic efficacy in children and adults with EoE. The investigators hypothesize that ESTs will capture an EoE Biomarker Panel (EBP) reflective of disease activity. The Specific Aims are to: (1) Identify an EoE Biomarker Panel (EBP) that will improve the sensitivity and specificity of the EST for monitoring disease activity and (2) Validate the ability of the EST EBP to monitor therapeutic efficacy in 1-hour sampling time. The investigators supportive Preliminary Data demonstrate the feasibility of using ESTs in both children and adults with EoE to measure disease activity (esophageal inflammation) in an overnight (12-hour) test, and shorter time periods, currently performed before a scheduled endoscopy with biopsy. In this project, The investigators propose to shorten this time frame to a 1-hour test, a clinically relevant time point that will markedly facilitate its use and potential impact in the outpatient clinic setting.

Public Health Relevance/Impacts: At least four major impacts should result from these studies:

(1) Identification of an EBP will permit monitoring of esophageal inflammation in EoE; (2) the EBP will be relevant to following disease progression, treatment responses, management and pathogenesis of EoE, (3) validation of the EST EBP will enable development of rapid and inexpensive assays to follow treatment responses, thus reducing the number of follow-up endoscopies with biopsy that are currently performed, and (4) provide a device to monitor EoE disease activity where endoscopy with biopsy may not be available or affordable.

Eligibility criteria: Inclusion Criteria:

* Patients undergoing esophagogastroduodenoscopy (EGD) at Children's Hospital Colorado, or
* Patients from a participating site in whom an inflammatory GI disease is suspected.
* Patients with symptoms of:

  1. abdominal pain,
  2. vomiting,
  3. growth delay, or
  4. malabsorption for which an etiology has not been determined.
* Patients with chronic eosinophilic esophagitis (EoE) in whom symptoms suggest ongoing inflammation.

Exclusion Criteria:

* Patients suffering from bleeding diathesis, or any other comorbid condition which their doctor feels may put them at additional risk.
* Patients with a family history of connective tissue disease.
* Patients undergoing a therapeutic endoscopy (such as dilatation, sclerotherapy, variceal banding).
* Patients with a history of:

  1. esophageal stricture, or
  2. surgery such as fundoplication, or
  3. allergy to gelatin, or
  4. inability to swallow pills.

Primary outcomes:
measure: Association of biomarker levels in biopsy tissue with pathological findings (eosinophil counts)
timeFrame: 12 weeks
Secondary outcomes:
measure: Correlation for the level of each biomarker between EST and tissue biopsy samples
timeFrame: 12 weeks
Other outcomes:
measure: Ability of an individual biomarker (or combination of biomarkers) to differentiate mucosal biopsy EBP sample obtained before and after treatment
timeFrame: 12 weeks
measure: Ability of an individual biomarker (or combination of biomarkers) to differentiate post-treatment mucosal biopsy EBP sample from normal control
timeFrame: 12 weeks
Locations:
city: Aurora
country: United States
facility: Children's Hospital Colorado
state: Colorado
city: Aurora
country: United States
facility: University of Colorado Hospital
state: Colorado
city: Chicago
country: United States
facility: Northwestern University
state: Illinois
city: Chicago
country: United States
facility: Lurie Children's Hospital
state: Illinois
city: Peoria
country: United States
facility: OSF St Francis Medical Center
state: Illinois
city: Indianapolis
country: United States
facility: Indiana University
state: Indiana
Study officials:
affiliation: Children's Hospital Colorado
name: Glenn T Furuta, MD
role: PRINCIPAL_INVESTIGATOR
References:
citation: Furuta GT, Kagalwalla AF, Lee JJ, Alumkal P, Maybruck BT, Fillon S, Masterson JC, Ochkur S, Protheroe C, Moore W, Pan Z, Amsden K, Robinson Z, Capocelli K, Mukkada V, Atkins D, Fleischer D, Hosford L, Kwatia MA, Schroeder S, Kelly C, Lovell M, Melin-Aldana H, Ackerman SJ. The oesophageal string test: a novel, minimally invasive method measures mucosal inflammation in eosinophilic oesophagitis. Gut. 2013 Oct;62(10):1395-405. doi: 10.1136/gutjnl-2012-303171. Epub 2012 Aug 15.
citation: Ackerman SJ, Kagalwalla AF, Hirano I, Gonsalves N, Katcher PM, Gupta S, Wechsler JB, Grozdanovic M, Pan Z, Masterson JC, Du J, Fantus RJ, Alumkal P, Lee JJ, Ochkur S, Ahmed F, Capocelli K, Melin-Aldana H, Biette K, Dubner A, Amsden K, Keeley K, Sulkowski M, Zalewski A, Atkins D, Furuta GT. One-Hour Esophageal String Test: A Nonendoscopic Minimally Invasive Test That Accurately Detects Disease Activity in Eosinophilic Esophagitis. Am J Gastroenterol. 2019 Oct;114(10):1614-1625. doi: 10.14309/ajg.0000000000000371.