<clinical_study>
  <!-- This xml conforms to an XML Schema at:
    https://clinicaltrials.gov/ct2/html/images/info/public.xsd -->
  <required_header>
    <download_date>ClinicalTrials.gov processed this data on September 20, 2023</download_date>
    <link_text>Link to the current ClinicalTrials.gov record.</link_text>
    <url>https://clinicaltrials.gov/ct2/show/NCT03822325</url>
  </required_header>
  <id_info>
    <org_study_id>2010-14155</org_study_id>
    <nct_id>NCT03822325</nct_id>
  </id_info>
  <brief_title>Inflammatory Mediators as Potential Non-Invasive Biomarkers in Subjects With Eosinophilic Esophagitis</brief_title>
  <official_title>Inflammatory Mediators as Potential Non-Invasive Biomarkers and Understanding the Mechanism of Remodeling in Tissue Biopsies in Subjects With Eosinophilic Esophagitis: A Pilot Study</official_title>
  <sponsors>
    <lead_sponsor>
      <agency>Ann &amp; Robert H Lurie Children's Hospital of Chicago</agency>
      <agency_class>Other</agency_class>
    </lead_sponsor>
  </sponsors>
  <source>Ann &amp; Robert H Lurie Children's Hospital of Chicago</source>
  <oversight_info>
    <has_dmc>No</has_dmc>
    <is_fda_regulated_drug>No</is_fda_regulated_drug>
    <is_fda_regulated_device>No</is_fda_regulated_device>
  </oversight_info>
  <brief_summary>
    <textblock>
      The investigators seek to assess esophageal inflammation or lack of it in response to&#xD;
      treatment with a novel non-invasive method that would measure eosinophil-associated&#xD;
      inflammatory mediators in the blood and urine to determine the presence of active&#xD;
      Eosinophilic Esophagitis. For these purposes, the investigators will correlate esophageal&#xD;
      inflammatory mediators measured in blood and urine with histological findings identified on&#xD;
      esophageal mucosal biopsies. Additionally, biopsies associated mediators will be assessed&#xD;
      relative to clinical phenotype and outcome.&#xD;
    </textblock>
  </brief_summary>
  <detailed_description>
    <textblock>
      The diagnosis, assessment of recurrence of inflammation, response to treatment and remission&#xD;
      in EoE are all currently based on histological evaluation of upper endoscopic pinch&#xD;
      esophageal biopsies. Obtaining biopsies for histological evaluation by this procedure is both&#xD;
      invasive and expensive. The purpose of our longitudinal prospective study is to evaluate and&#xD;
      quantify a panel of novel non-invasive eosinophilic inflammatory biomarkers in the blood and&#xD;
      urine of subjects with EoE and compare their presence and levels with the presence or absence&#xD;
      of measures of inflammation in esophageal biopsies. While evaluation of esophageal biopsies&#xD;
      with 15 or more eosinophils per high power field is the gold standard for diagnosis of EoE,&#xD;
      novel predictors of clinical outcome remain unclear. The objective is to identify one or more&#xD;
      sensitive and specific non-invasive biomarkers that could be used to monitor esophageal&#xD;
      inflammation, and identify novel tissue-based markers that identify phenotype and outcome.&#xD;
      This would eliminate the need for invasive serial surveillance endoscopies for the purpose of&#xD;
      evaluating for recurrence of inflammation or response to standard therapy since symptoms&#xD;
      alone do not adequately correlate with either the presence or absence of disease activity&#xD;
      (inflammation) in the esophagus of patients with EoE.&#xD;
    </textblock>
  </detailed_description>
  <overall_status>Active, not recruiting</overall_status>
  <start_date type="Actual">February 2011</start_date>
  <completion_date type="Anticipated">May 2025</completion_date>
  <primary_completion_date type="Actual">May 2015</primary_completion_date>
  <study_type>Observational [Patient Registry]</study_type>
  <has_expanded_access>No</has_expanded_access>
  <study_design_info>
    <observational_model>Cohort</observational_model>
    <time_perspective>Prospective</time_perspective>
  </study_design_info>
  <target_duration>5 Years</target_duration>
  <primary_outcome>
    <measure>Correlate RNA and protein measures from esophageal biopsies with histologic, endoscopic and clinical aspects of disease along with non-invasive biomarkers</measure>
    <time_frame>5 years</time_frame>
    <description>Frozen biopsies and archived slides from EoE patients and controls will be used in testing molecules released by or expressed on the cell surface of inflammatory cells. The molecules will be assessed using RNA sequencing, ELISA, and immunohistochemistry. This information will be correlated with eosinophil counts along with endoscopy findings, treatment outcomes and clinical measures of the disease such as symptoms, atopic co-morbidities, and demographics.</description>
  </primary_outcome>
  <enrollment type="Actual">88</enrollment>
  <condition>Eosinophilic Esophagitis</condition>
  <biospec_retention>Samples With DNA</biospec_retention>
  <biospec_descr>
    <textblock>
      The investigators collected biopsies, blood, and urine from enrolled participants.&#xD;
    </textblock>
  </biospec_descr>
  <eligibility>
    <study_pop>
      <textblock>
        Any patient undergoing a clinically indicated upper endoscopy with biopsy for suspected&#xD;
        esophageal inflammation or esophageal disease, or who has histologically confirmed&#xD;
        esophageal inflammation may be asked to enroll in this study. The investigators plan to&#xD;
        recruit subjects for two years, and enroll up to 150 patients. The patients with a&#xD;
        confirmed diagnosis of EoE will be followed in the study for two years after enrollment.&#xD;
      </textblock>
    </study_pop>
    <sampling_method>Non-Probability Sample</sampling_method>
    <criteria>
      <textblock>
        Inclusion Criteria:&#xD;
&#xD;
          -  Patient ages 1-18 undergoing upper endoscopy for suspected esophageal disease or&#xD;
             esophageal inflammation or has histologically confirmed esophageal inflammation may be&#xD;
             included in this study&#xD;
&#xD;
        Exclusion Criteria:&#xD;
&#xD;
          -  Patients with a history or current diagnosis of esophageal malignancy or subjects with&#xD;
             graft versus host disease will be excluded from the study.&#xD;
&#xD;
          -  Patients that are considered at high risk for biopsies at the discretion of the&#xD;
             child's physician and/or the researcher&#xD;
&#xD;
          -  Patients with known bleeding disorders or patients with illnesses where bleeding would&#xD;
             pose a threat to their health&#xD;
&#xD;
          -  Diagnosis other than Eosinophilic Esophagitis (EoE) i.e. Inflammatory Bowel Disease&#xD;
             (IBD), Gastroesophageal Reflux Disease (GERD)&#xD;
      </textblock>
    </criteria>
    <gender>All</gender>
    <minimum_age>1 Year</minimum_age>
    <maximum_age>18 Years</maximum_age>
    <healthy_volunteers>Accepts Healthy Volunteers</healthy_volunteers>
  </eligibility>
  <overall_official>
    <last_name>Joshua Wechsler, MD</last_name>
    <role>Principal Investigator</role>
    <affiliation>Ann &amp; Robert H Lurie Children's Hospital of Chicago</affiliation>
  </overall_official>
  <overall_official>
    <last_name>Barry Wershil, MD</last_name>
    <role>Principal Investigator</role>
    <affiliation>Ann &amp; Robert H. Lurie Children's Hospital fo Chicago</affiliation>
  </overall_official>
  <location>
    <facility>
      <name>Ann &amp; Robert H Lurie Childjren's Hospital of Chicago</name>
      <address>
        <city>Chicago</city>
        <state>Illinois</state>
        <zip>60611</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>University of Illinois at Chicago (UIC)</name>
      <address>
        <city>Chicago</city>
        <state>Illinois</state>
        <zip>60612</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location_countries>
    <country>United States</country>
  </location_countries>
  <reference>
    <citation>Dellon ES, Hirano I. Epidemiology and Natural History of Eosinophilic Esophagitis. Gastroenterology. 2018 Jan;154(2):319-332.e3. doi: 10.1053/j.gastro.2017.06.067. Epub 2017 Aug 1.</citation>
    <PMID>28774845</PMID>
  </reference>
  <reference>
    <citation>O'Shea KM, Aceves SS, Dellon ES, Gupta SK, Spergel JM, Furuta GT, Rothenberg ME. Pathophysiology of Eosinophilic Esophagitis. Gastroenterology. 2018 Jan;154(2):333-345. doi: 10.1053/j.gastro.2017.06.065. Epub 2017 Jul 27.</citation>
    <PMID>28757265</PMID>
  </reference>
  <reference>
    <citation>Jensen ET, Kappelman MD, Martin CF, Dellon ES. Health-care utilization, costs, and the burden of disease related to eosinophilic esophagitis in the United States. Am J Gastroenterol. 2015 May;110(5):626-32. doi: 10.1038/ajg.2014.316. Epub 2014 Sep 30.</citation>
    <PMID>25267327</PMID>
  </reference>
  <reference>
    <citation>Furuta GT, Katzka DA. Eosinophilic Esophagitis. N Engl J Med. 2015 Oct 22;373(17):1640-8. doi: 10.1056/NEJMra1502863.</citation>
    <PMID>26488694</PMID>
  </reference>
  <reference>
    <citation>Steinbach EC, Hernandez M, Dellon ES. Eosinophilic Esophagitis and the Eosinophilic Gastrointestinal Diseases: Approach to Diagnosis and Management. J Allergy Clin Immunol Pract. 2018 Sep-Oct;6(5):1483-1495. doi: 10.1016/j.jaip.2018.06.012. Epub 2018 Jul 3.</citation>
    <PMID>30201096</PMID>
  </reference>
  <reference>
    <citation>Dellon ES, Liacouras CA, Molina-Infante J, Furuta GT, Spergel JM, Zevit N, Spechler SJ, Attwood SE, Straumann A, Aceves SS, Alexander JA, Atkins D, Arva NC, Blanchard C, Bonis PA, Book WM, Capocelli KE, Chehade M, Cheng E, Collins MH, Davis CM, Dias JA, Di Lorenzo C, Dohil R, Dupont C, Falk GW, Ferreira CT, Fox A, Gonsalves NP, Gupta SK, Katzka DA, Kinoshita Y, Menard-Katcher C, Kodroff E, Metz DC, Miehlke S, Muir AB, Mukkada VA, Murch S, Nurko S, Ohtsuka Y, Orel R, Papadopoulou A, Peterson KA, Philpott H, Putnam PE, Richter JE, Rosen R, Rothenberg ME, Schoepfer A, Scott MM, Shah N, Sheikh J, Souza RF, Strobel MJ, Talley NJ, Vaezi MF, Vandenplas Y, Vieira MC, Walker MM, Wechsler JB, Wershil BK, Wen T, Yang GY, Hirano I, Bredenoord AJ. Updated International Consensus Diagnostic Criteria for Eosinophilic Esophagitis: Proceedings of the AGREE Conference. Gastroenterology. 2018 Oct;155(4):1022-1033.e10. doi: 10.1053/j.gastro.2018.07.009. Epub 2018 Sep 6.</citation>
    <PMID>30009819</PMID>
  </reference>
  <reference>
    <citation>Godwin B, Wilkins B, Muir AB. EoE disease monitoring: Where we are and where we are going. Ann Allergy Asthma Immunol. 2020 Mar;124(3):240-247. doi: 10.1016/j.anai.2019.12.004. Epub 2019 Dec 9.</citation>
    <PMID>31830586</PMID>
  </reference>
  <reference>
    <citation>Carlson DA, Lin Z, Hirano I, Gonsalves N, Zalewski A, Pandolfino JE. Evaluation of esophageal distensibility in eosinophilic esophagitis: an update and comparison of functional lumen imaging probe analytic methods. Neurogastroenterol Motil. 2016 Dec;28(12):1844-1853. doi: 10.1111/nmo.12888. Epub 2016 Jun 16.</citation>
    <PMID>27311807</PMID>
  </reference>
  <reference>
    <citation>Abonia JP, Wen T, Stucke EM, Grotjan T, Griffith MS, Kemme KA, Collins MH, Putnam PE, Franciosi JP, von Tiehl KF, Tinkle BT, Marsolo KA, Martin LJ, Ware SM, Rothenberg ME. High prevalence of eosinophilic esophagitis in patients with inherited connective tissue disorders. J Allergy Clin Immunol. 2013 Aug;132(2):378-86. doi: 10.1016/j.jaci.2013.02.030. Epub 2013 Apr 19.</citation>
    <PMID>23608731</PMID>
  </reference>
  <reference>
    <citation>Tinkle BT, Levy HP. Symptomatic Joint Hypermobility: The Hypermobile Type of Ehlers-Danlos Syndrome and the Hypermobility Spectrum Disorders. Med Clin North Am. 2019 Nov;103(6):1021-1033. doi: 10.1016/j.mcna.2019.08.002.</citation>
    <PMID>31582002</PMID>
  </reference>
  <reference>
    <citation>Huang KZ, Dellon ES. Increased prevalence of autonomic dysfunction due to postural orthostatic tachycardia syndrome in patients with eosinophilic gastrointestinal disorders. J Gastrointestin Liver Dis. 2019 Mar;28(1):47-51. doi: 10.15403/jgld.2014.1121.281.syd.</citation>
    <PMID>30851172</PMID>
  </reference>
  <reference>
    <citation>Fikree A, Aziz Q, Sifrim D. Mechanisms underlying reflux symptoms and dysphagia in patients with joint hypermobility syndrome, with and without postural tachycardia syndrome. Neurogastroenterol Motil. 2017 Jun;29(6). doi: 10.1111/nmo.13029. Epub 2017 Feb 12.</citation>
    <PMID>28191707</PMID>
  </reference>
  <verification_date>August 2023</verification_date>
  <study_first_submitted>August 16, 2018</study_first_submitted>
  <study_first_submitted_qc>January 28, 2019</study_first_submitted_qc>
  <study_first_posted type="Actual">January 30, 2019</study_first_posted>
  <last_update_submitted>August 31, 2023</last_update_submitted>
  <last_update_submitted_qc>August 31, 2023</last_update_submitted_qc>
  <last_update_posted type="Actual">September 1, 2023</last_update_posted>
  <responsible_party>
    <responsible_party_type>Principal Investigator</responsible_party_type>
    <investigator_affiliation>Ann &amp; Robert H Lurie Children's Hospital of Chicago</investigator_affiliation>
    <investigator_full_name>Joshua Wechsler</investigator_full_name>
    <investigator_title>Attending Physician, Gastroenterology, Hepatology &amp; Nutrition</investigator_title>
  </responsible_party>
  <condition_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Esophagitis</mesh_term>
    <mesh_term>Eosinophilic Esophagitis</mesh_term>
  </condition_browse>
  <patient_data>
    <sharing_ipd>Undecided</sharing_ipd>
  </patient_data>
  <!-- Results have not yet been posted for this study                                          -->
</clinical_study>


download date: ClinicalTrials.gov processed this data on September 20, 2023
link text: Link to the current ClinicalTrials.gov record.
url: https://clinicaltrials.gov/ct2/show/NCT03822325
org study id: 2010-14155
nct id: NCT03822325
lead sponsor: 
has dmc: No
is fda regulated drug: No
is fda regulated device: No
The investigators seek to assess esophageal inflammation or lack of it in response to
      treatment with a novel non-invasive method that would measure eosinophil-associated
      inflammatory mediators in the blood and urine to determine the presence of active
      Eosinophilic Esophagitis. For these purposes, the investigators will correlate esophageal
      inflammatory mediators measured in blood and urine with histological findings identified on
      esophageal mucosal biopsies. Additionally, biopsies associated mediators will be assessed
      relative to clinical phenotype and outcome.
The diagnosis, assessment of recurrence of inflammation, response to treatment and remission
      in EoE are all currently based on histological evaluation of upper endoscopic pinch
      esophageal biopsies. Obtaining biopsies for histological evaluation by this procedure is both
      invasive and expensive. The purpose of our longitudinal prospective study is to evaluate and
      quantify a panel of novel non-invasive eosinophilic inflammatory biomarkers in the blood and
      urine of subjects with EoE and compare their presence and levels with the presence or absence
      of measures of inflammation in esophageal biopsies. While evaluation of esophageal biopsies
      with 15 or more eosinophils per high power field is the gold standard for diagnosis of EoE,
      novel predictors of clinical outcome remain unclear. The objective is to identify one or more
      sensitive and specific non-invasive biomarkers that could be used to monitor esophageal
      inflammation, and identify novel tissue-based markers that identify phenotype and outcome.
      This would eliminate the need for invasive serial surveillance endoscopies for the purpose of
      evaluating for recurrence of inflammation or response to standard therapy since symptoms
      alone do not adequately correlate with either the presence or absence of disease activity
      (inflammation) in the esophagus of patients with EoE.
observational model: Cohort
time perspective: Prospective
measure: Correlate RNA and protein measures from esophageal biopsies with histologic, endoscopic and clinical aspects of disease along with non-invasive biomarkers
time frame: 5 years
description: Frozen biopsies and archived slides from EoE patients and controls will be used in testing molecules released by or expressed on the cell surface of inflammatory cells. The molecules will be assessed using RNA sequencing, ELISA, and immunohistochemistry. This information will be correlated with eosinophil counts along with endoscopy findings, treatment outcomes and clinical measures of the disease such as symptoms, atopic co-morbidities, and demographics.
The investigators collected biopsies, blood, and urine from enrolled participants.
study pop: 
sampling method: Non-Probability Sample
criteria: 
gender: All
minimum age: 1 Year
maximum age: 18 Years
healthy volunteers: Accepts Healthy Volunteers
last name: Joshua Wechsler, MD
role: Principal Investigator
affiliation: Ann & Robert H Lurie Children's Hospital of Chicago
last name: Barry Wershil, MD
role: Principal Investigator
affiliation: Ann & Robert H. Lurie Children's Hospital fo Chicago
facility: 
facility: 
country: United States
citation: Dellon ES, Hirano I. Epidemiology and Natural History of Eosinophilic Esophagitis. Gastroenterology. 2018 Jan;154(2):319-332.e3. doi: 10.1053/j.gastro.2017.06.067. Epub 2017 Aug 1.
PMID: 28774845
citation: O'Shea KM, Aceves SS, Dellon ES, Gupta SK, Spergel JM, Furuta GT, Rothenberg ME. Pathophysiology of Eosinophilic Esophagitis. Gastroenterology. 2018 Jan;154(2):333-345. doi: 10.1053/j.gastro.2017.06.065. Epub 2017 Jul 27.
PMID: 28757265
citation: Jensen ET, Kappelman MD, Martin CF, Dellon ES. Health-care utilization, costs, and the burden of disease related to eosinophilic esophagitis in the United States. Am J Gastroenterol. 2015 May;110(5):626-32. doi: 10.1038/ajg.2014.316. Epub 2014 Sep 30.
PMID: 25267327
citation: Furuta GT, Katzka DA. Eosinophilic Esophagitis. N Engl J Med. 2015 Oct 22;373(17):1640-8. doi: 10.1056/NEJMra1502863.
PMID: 26488694
citation: Steinbach EC, Hernandez M, Dellon ES. Eosinophilic Esophagitis and the Eosinophilic Gastrointestinal Diseases: Approach to Diagnosis and Management. J Allergy Clin Immunol Pract. 2018 Sep-Oct;6(5):1483-1495. doi: 10.1016/j.jaip.2018.06.012. Epub 2018 Jul 3.
PMID: 30201096
citation: Dellon ES, Liacouras CA, Molina-Infante J, Furuta GT, Spergel JM, Zevit N, Spechler SJ, Attwood SE, Straumann A, Aceves SS, Alexander JA, Atkins D, Arva NC, Blanchard C, Bonis PA, Book WM, Capocelli KE, Chehade M, Cheng E, Collins MH, Davis CM, Dias JA, Di Lorenzo C, Dohil R, Dupont C, Falk GW, Ferreira CT, Fox A, Gonsalves NP, Gupta SK, Katzka DA, Kinoshita Y, Menard-Katcher C, Kodroff E, Metz DC, Miehlke S, Muir AB, Mukkada VA, Murch S, Nurko S, Ohtsuka Y, Orel R, Papadopoulou A, Peterson KA, Philpott H, Putnam PE, Richter JE, Rosen R, Rothenberg ME, Schoepfer A, Scott MM, Shah N, Sheikh J, Souza RF, Strobel MJ, Talley NJ, Vaezi MF, Vandenplas Y, Vieira MC, Walker MM, Wechsler JB, Wershil BK, Wen T, Yang GY, Hirano I, Bredenoord AJ. Updated International Consensus Diagnostic Criteria for Eosinophilic Esophagitis: Proceedings of the AGREE Conference. Gastroenterology. 2018 Oct;155(4):1022-1033.e10. doi: 10.1053/j.gastro.2018.07.009. Epub 2018 Sep 6.
PMID: 30009819
citation: Godwin B, Wilkins B, Muir AB. EoE disease monitoring: Where we are and where we are going. Ann Allergy Asthma Immunol. 2020 Mar;124(3):240-247. doi: 10.1016/j.anai.2019.12.004. Epub 2019 Dec 9.
PMID: 31830586
citation: Carlson DA, Lin Z, Hirano I, Gonsalves N, Zalewski A, Pandolfino JE. Evaluation of esophageal distensibility in eosinophilic esophagitis: an update and comparison of functional lumen imaging probe analytic methods. Neurogastroenterol Motil. 2016 Dec;28(12):1844-1853. doi: 10.1111/nmo.12888. Epub 2016 Jun 16.
PMID: 27311807
citation: Abonia JP, Wen T, Stucke EM, Grotjan T, Griffith MS, Kemme KA, Collins MH, Putnam PE, Franciosi JP, von Tiehl KF, Tinkle BT, Marsolo KA, Martin LJ, Ware SM, Rothenberg ME. High prevalence of eosinophilic esophagitis in patients with inherited connective tissue disorders. J Allergy Clin Immunol. 2013 Aug;132(2):378-86. doi: 10.1016/j.jaci.2013.02.030. Epub 2013 Apr 19.
PMID: 23608731
citation: Tinkle BT, Levy HP. Symptomatic Joint Hypermobility: The Hypermobile Type of Ehlers-Danlos Syndrome and the Hypermobility Spectrum Disorders. Med Clin North Am. 2019 Nov;103(6):1021-1033. doi: 10.1016/j.mcna.2019.08.002.
PMID: 31582002
citation: Huang KZ, Dellon ES. Increased prevalence of autonomic dysfunction due to postural orthostatic tachycardia syndrome in patients with eosinophilic gastrointestinal disorders. J Gastrointestin Liver Dis. 2019 Mar;28(1):47-51. doi: 10.15403/jgld.2014.1121.281.syd.
PMID: 30851172
citation: Fikree A, Aziz Q, Sifrim D. Mechanisms underlying reflux symptoms and dysphagia in patients with joint hypermobility syndrome, with and without postural tachycardia syndrome. Neurogastroenterol Motil. 2017 Jun;29(6). doi: 10.1111/nmo.13029. Epub 2017 Feb 12.
PMID: 28191707
responsible party type: Principal Investigator
investigator affiliation: Ann & Robert H Lurie Children's Hospital of Chicago
investigator full name: Joshua Wechsler
investigator title: Attending Physician, Gastroenterology, Hepatology & Nutrition
mesh term: Esophagitis
mesh term: Eosinophilic Esophagitis
sharing ipd: Undecided