<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/NCT04416217</url>
  </required_header>
  <id_info>
    <org_study_id>0521-19-RMC</org_study_id>
    <nct_id>NCT04416217</nct_id>
  </id_info>
  <brief_title>Eosinophilic Esophagitis Steroid Safety Study</brief_title>
  <acronym>EESY</acronym>
  <official_title>Adrenal Suppression in Pediatric Eosinophilic Esophagitis Treated With Topical Steroids - A Multicenter, Prospective, Observational Safety Study</official_title>
  <sponsors>
    <lead_sponsor>
      <agency>Rabin Medical Center</agency>
      <agency_class>Other</agency_class>
    </lead_sponsor>
  </sponsors>
  <source>Rabin Medical Center</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>
      This observational study will follow pediatric patients with eosinophilic esophagitis who are&#xD;
      scheduled to begin topical steroid treatment, from the initiation of treatment longitudinally&#xD;
      to determine the safety profile of the drug.&#xD;
    </textblock>
  </brief_summary>
  <overall_status>Recruiting</overall_status>
  <start_date type="Actual">October 7, 2019</start_date>
  <completion_date type="Anticipated">December 31, 2025</completion_date>
  <primary_completion_date type="Anticipated">December 31, 2025</primary_completion_date>
  <study_type>Observational</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>
  <primary_outcome>
    <measure>Adrenal suppression</measure>
    <time_frame>3 months</time_frame>
    <description>Rates of pathological adrenocorticotropic hormone (ACTH) tests at 3 and 12 months of topical steroid use</description>
  </primary_outcome>
  <primary_outcome>
    <measure>Adrenal suppression</measure>
    <time_frame>12 months</time_frame>
    <description>Rates of pathological adrenocorticotropic hormone (ACTH) tests at 3 and 12 months of topical steroid use</description>
  </primary_outcome>
  <primary_outcome>
    <measure>Growth failure</measure>
    <time_frame>12 months</time_frame>
    <description>Rates of decreased Height for age after 12 months of treatment.</description>
  </primary_outcome>
  <primary_outcome>
    <measure>Growth failure</measure>
    <time_frame>36 months</time_frame>
    <description>Rates of decreased Height for age after 12 months of treatment.</description>
  </primary_outcome>
  <secondary_outcome>
    <measure>Bone mineral density</measure>
    <time_frame>12 months</time_frame>
    <description>Decrease in bone mineral density between first and second dual energy x-ray absorptiometry (DEXA)</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Bone mineral density</measure>
    <time_frame>3 years</time_frame>
    <description>Decrease in bone mineral density between first and second dual energy x-ray absorptiometry (DEXA)</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Hyperglycemia</measure>
    <time_frame>3 months</time_frame>
    <description>Rates of elevated fasting glucose after 3 and 12 months of treatment</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Hyperglycemia</measure>
    <time_frame>12 months</time_frame>
    <description>Rates of elevated fasting glucose after 3 and 12 months of treatment</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Elevated Liver Enzymes</measure>
    <time_frame>3 months</time_frame>
    <description>Elevated ALT</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Histological remission 3 months</measure>
    <time_frame>3 months</time_frame>
    <description>Histological remission at endoscopy timepoints</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Histological remission 12 months</measure>
    <time_frame>12 months</time_frame>
    <description>Histological remission at endoscopy timepoints</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Clinical remission</measure>
    <time_frame>3 months</time_frame>
    <description>Clinical remission at endoscopy time points according to PEESS v.2</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Clinical remission</measure>
    <time_frame>12 months</time_frame>
    <description>Clinical remission at endoscopy time points according to PEESS v.2</description>
  </secondary_outcome>
  <number_of_groups>1</number_of_groups>
  <enrollment type="Anticipated">300</enrollment>
  <condition>Eosinophilic Esophagitis</condition>
  <arm_group>
    <arm_group_label>Topical Steroid Treatment</arm_group_label>
    <description>Pediatric patients with eosinophilic esophagitis scheduled to begin topical steroid treatment for the treatment of their condition. The type of topical steroid is not limited and is at the discretion of the treating physician as are dosing and concomitant treatments.</description>
  </arm_group>
  <eligibility>
    <study_pop>
      <textblock>
        Pediatric patients diagnosed with eosinophilic esophagitis for whom following discussion&#xD;
        between the patient/gaurdians and physician treatment with topical steroids are planned.&#xD;
      </textblock>
    </study_pop>
    <sampling_method>Non-Probability Sample</sampling_method>
    <criteria>
      <textblock>
        Inclusion Criteria:&#xD;
&#xD;
          1. Age &lt;18 years at the time of enrollment.&#xD;
&#xD;
          2. Males and Females are included.&#xD;
&#xD;
          3. Patients diagnosed with EoE as defined by age appropriate signs of esophageal&#xD;
             dysfunction (in older children and adolescents - dysphagia, impacted food bolus,&#xD;
             foreign body impaction, vomiting, and GERD not responsive to high dose proton pump&#xD;
             inhibitors. In infants and young children - failure to thrive, poor feeding, vomiting,&#xD;
             food bolus impaction)&#xD;
&#xD;
          4. Histopathological finding of ≥15 eosinophils/high power field (X400) on at least one&#xD;
             esophageal biopsy.&#xD;
&#xD;
          5. After discussing the available treatment options with the gastroenterologist, the&#xD;
             patient has chosen oral topical steroid treatment (either as a first treatment or&#xD;
             after failure of other dietary or medical treatment).&#xD;
&#xD;
        Exclusion Criteria:&#xD;
&#xD;
          1. Known alternative causes of esophageal eosinophilia.&#xD;
&#xD;
          2. Legal guardian unable or unwilling to sign informed consent..&#xD;
&#xD;
          3. Known allergy to topical steroids ingredients&#xD;
&#xD;
          4. Patient will not be available for follow-up for at least the 3 month assessment and&#xD;
             ACTH test.&#xD;
&#xD;
          5. Known pregnancy&#xD;
&#xD;
          6. Use of oral systemic steroids in the 6 months prior to inclusion in the study. Use of&#xD;
             systemic steroids once in the study will not lead to study termination, but such use&#xD;
             will need to be reported in the medication changes and use page of the following&#xD;
             visit.&#xD;
      </textblock>
    </criteria>
    <gender>All</gender>
    <minimum_age>N/A</minimum_age>
    <maximum_age>18 Years</maximum_age>
    <healthy_volunteers>No</healthy_volunteers>
  </eligibility>
  <overall_contact>
    <last_name>Noam Zevit, M.D.</last_name>
    <phone>972-3-9253673</phone>
    <email>nzevit@gmail.com</email>
  </overall_contact>
  <overall_contact_backup>
    <last_name>Reut Klein</last_name>
    <phone>972-3-9253039</phone>
    <email>reutkl@clalit.org.il</email>
  </overall_contact_backup>
  <location>
    <facility>
      <name>Athens Children's Hospital &quot;AGIA SOPHIA&quot;</name>
      <address>
        <city>Athens</city>
        <zip>115 27</zip>
        <country>Greece</country>
      </address>
    </facility>
    <status>Recruiting</status>
    <contact>
      <last_name>Alexandra Papadopoulou, M.D.</last_name>
      <phone>210 74 67 945</phone>
      <email>a.papadopoulou@paidon-agiasofia.gr</email>
    </contact>
  </location>
  <location>
    <facility>
      <name>Institute of Gastroenterology, Nutrition and Liver Diseases; Schneider Children's Medical Center of Israel</name>
      <address>
        <city>Petach Tikva</city>
        <zip>49202</zip>
        <country>Israel</country>
      </address>
    </facility>
    <status>Recruiting</status>
    <contact>
      <last_name>Noam Zevit, M.D.</last_name>
      <phone>972-3-9253673</phone>
      <email>noamze@clalit.org.il</email>
    </contact>
    <investigator>
      <last_name>Noam Zevit, M.D.</last_name>
      <role>Principal Investigator</role>
    </investigator>
  </location>
  <location>
    <facility>
      <name>Department of Woman, Child and General and Specialized Surgery, University of the Campania &quot;Luigi Vanvitelli&quot;</name>
      <address>
        <city>Naples</city>
        <country>Italy</country>
      </address>
    </facility>
    <status>Recruiting</status>
    <contact>
      <last_name>Caterina Strisciuglio</last_name>
    </contact>
    <contact_backup>
      <email>caterina.strisciuglio@unicampania.it</email>
    </contact_backup>
  </location>
  <location>
    <facility>
      <name>Maternal and Child Health Department, Sapienza</name>
      <address>
        <city>Rome</city>
        <country>Italy</country>
      </address>
    </facility>
    <status>Recruiting</status>
    <contact>
      <last_name>Salvatore Oliva, M.D.</last_name>
    </contact>
    <contact_backup>
      <email>salvatore.oliva@uniroma1.it</email>
    </contact_backup>
  </location>
  <location_countries>
    <country>Greece</country>
    <country>Israel</country>
    <country>Italy</country>
  </location_countries>
  <reference>
    <citation>Lucendo AJ, Molina-Infante J, Arias A, von Arnim U, Bredenoord AJ, Bussmann C, Amil Dias J, Bove M, Gonzalez-Cervera J, Larsson H, Miehlke S, Papadopoulou A, Rodriguez-Sanchez J, Ravelli A, Ronkainen J, Santander C, Schoepfer AM, Storr MA, Terreehorst I, Straumann A, Attwood SE. Guidelines on eosinophilic esophagitis: evidence-based statements and recommendations for diagnosis and management in children and adults. United European Gastroenterol J. 2017 Apr;5(3):335-358. doi: 10.1177/2050640616689525. Epub 2017 Jan 23.</citation>
    <PMID>28507746</PMID>
  </reference>
  <reference>
    <citation>Hsu S, Wood C, Pan Z, Rahat H, Zeitler P, Fleischer D, Menard-Katcher C, Furuta GT, Atkins D. Adrenal Insufficiency in Pediatric Eosinophilic Esophagitis Patients Treated with Swallowed Topical Steroids. Pediatr Allergy Immunol Pulmonol. 2017 Sep 1;30(3):135-140. doi: 10.1089/ped.2017.0779.</citation>
    <PMID>29062584</PMID>
  </reference>
  <reference>
    <citation>Golekoh MC, Hornung LN, Mukkada VA, Khoury JC, Putnam PE, Backeljauw PF. Adrenal Insufficiency after Chronic Swallowed Glucocorticoid Therapy for Eosinophilic Esophagitis. J Pediatr. 2016 Mar;170:240-5. doi: 10.1016/j.jpeds.2015.11.026. Epub 2015 Dec 11.</citation>
    <PMID>26687577</PMID>
  </reference>
  <reference>
    <citation>Harel S, Hursh BE, Chan ES, Avinashi V, Panagiotopoulos C. Adrenal insufficiency exists for both swallowed budesonide and fluticasone propionate in the treatment of eosinophilic esophagitis. J Pediatr. 2016 Jul;174:281. doi: 10.1016/j.jpeds.2016.02.056. Epub 2016 Mar 19. No abstract available.</citation>
    <PMID>27004676</PMID>
  </reference>
  <reference>
    <citation>Philpott H, Dougherty MK, Reed CC, Caldwell M, Kirk D, Torpy DJ, Dellon ES. Systematic review: adrenal insufficiency secondary to swallowed topical corticosteroids in eosinophilic oesophagitis. Aliment Pharmacol Ther. 2018 Apr;47(8):1071-1078. doi: 10.1111/apt.14573. Epub 2018 Mar 5.</citation>
    <PMID>29508432</PMID>
  </reference>
  <verification_date>March 2023</verification_date>
  <study_first_submitted>May 24, 2020</study_first_submitted>
  <study_first_submitted_qc>June 1, 2020</study_first_submitted_qc>
  <study_first_posted type="Actual">June 4, 2020</study_first_posted>
  <last_update_submitted>March 28, 2023</last_update_submitted>
  <last_update_submitted_qc>March 28, 2023</last_update_submitted_qc>
  <last_update_posted type="Actual">March 30, 2023</last_update_posted>
  <responsible_party>
    <responsible_party_type>Principal Investigator</responsible_party_type>
    <investigator_affiliation>Schneider Children's Medical Center, Israel</investigator_affiliation>
    <investigator_full_name>Noam Zevit</investigator_full_name>
    <investigator_title>Attending Pediatric Gastroenterologist</investigator_title>
  </responsible_party>
  <keyword>Steroid , bone mineral density , DEXA , Adrenal</keyword>
  <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>
  <!-- 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/NCT04416217
org study id: 0521-19-RMC
nct id: NCT04416217
lead sponsor: 
has dmc: No
is fda regulated drug: No
is fda regulated device: No
This observational study will follow pediatric patients with eosinophilic esophagitis who are
      scheduled to begin topical steroid treatment, from the initiation of treatment longitudinally
      to determine the safety profile of the drug.
observational model: Cohort
time perspective: Prospective
measure: Adrenal suppression
time frame: 3 months
description: Rates of pathological adrenocorticotropic hormone (ACTH) tests at 3 and 12 months of topical steroid use
measure: Adrenal suppression
time frame: 12 months
description: Rates of pathological adrenocorticotropic hormone (ACTH) tests at 3 and 12 months of topical steroid use
measure: Growth failure
time frame: 12 months
description: Rates of decreased Height for age after 12 months of treatment.
measure: Growth failure
time frame: 36 months
description: Rates of decreased Height for age after 12 months of treatment.
measure: Bone mineral density
time frame: 12 months
description: Decrease in bone mineral density between first and second dual energy x-ray absorptiometry (DEXA)
measure: Bone mineral density
time frame: 3 years
description: Decrease in bone mineral density between first and second dual energy x-ray absorptiometry (DEXA)
measure: Hyperglycemia
time frame: 3 months
description: Rates of elevated fasting glucose after 3 and 12 months of treatment
measure: Hyperglycemia
time frame: 12 months
description: Rates of elevated fasting glucose after 3 and 12 months of treatment
measure: Elevated Liver Enzymes
time frame: 3 months
description: Elevated ALT
measure: Histological remission 3 months
time frame: 3 months
description: Histological remission at endoscopy timepoints
measure: Histological remission 12 months
time frame: 12 months
description: Histological remission at endoscopy timepoints
measure: Clinical remission
time frame: 3 months
description: Clinical remission at endoscopy time points according to PEESS v.2
measure: Clinical remission
time frame: 12 months
description: Clinical remission at endoscopy time points according to PEESS v.2
arm group label: Topical Steroid Treatment
description: Pediatric patients with eosinophilic esophagitis scheduled to begin topical steroid treatment for the treatment of their condition. The type of topical steroid is not limited and is at the discretion of the treating physician as are dosing and concomitant treatments.
study pop: 
sampling method: Non-Probability Sample
criteria: 
gender: All
minimum age: N/A
maximum age: 18 Years
healthy volunteers: No
last name: Noam Zevit, M.D.
phone: 972-3-9253673
email: nzevit@gmail.com
last name: Reut Klein
phone: 972-3-9253039
email: reutkl@clalit.org.il
facility: 
status: Recruiting
contact: 
facility: 
status: Recruiting
contact: 
investigator: 
facility: 
status: Recruiting
contact: 
contact backup: 
facility: 
status: Recruiting
contact: 
contact backup: 
country: Greece
country: Israel
country: Italy
citation: Lucendo AJ, Molina-Infante J, Arias A, von Arnim U, Bredenoord AJ, Bussmann C, Amil Dias J, Bove M, Gonzalez-Cervera J, Larsson H, Miehlke S, Papadopoulou A, Rodriguez-Sanchez J, Ravelli A, Ronkainen J, Santander C, Schoepfer AM, Storr MA, Terreehorst I, Straumann A, Attwood SE. Guidelines on eosinophilic esophagitis: evidence-based statements and recommendations for diagnosis and management in children and adults. United European Gastroenterol J. 2017 Apr;5(3):335-358. doi: 10.1177/2050640616689525. Epub 2017 Jan 23.
PMID: 28507746
citation: Hsu S, Wood C, Pan Z, Rahat H, Zeitler P, Fleischer D, Menard-Katcher C, Furuta GT, Atkins D. Adrenal Insufficiency in Pediatric Eosinophilic Esophagitis Patients Treated with Swallowed Topical Steroids. Pediatr Allergy Immunol Pulmonol. 2017 Sep 1;30(3):135-140. doi: 10.1089/ped.2017.0779.
PMID: 29062584
citation: Golekoh MC, Hornung LN, Mukkada VA, Khoury JC, Putnam PE, Backeljauw PF. Adrenal Insufficiency after Chronic Swallowed Glucocorticoid Therapy for Eosinophilic Esophagitis. J Pediatr. 2016 Mar;170:240-5. doi: 10.1016/j.jpeds.2015.11.026. Epub 2015 Dec 11.
PMID: 26687577
citation: Harel S, Hursh BE, Chan ES, Avinashi V, Panagiotopoulos C. Adrenal insufficiency exists for both swallowed budesonide and fluticasone propionate in the treatment of eosinophilic esophagitis. J Pediatr. 2016 Jul;174:281. doi: 10.1016/j.jpeds.2016.02.056. Epub 2016 Mar 19. No abstract available.
PMID: 27004676
citation: Philpott H, Dougherty MK, Reed CC, Caldwell M, Kirk D, Torpy DJ, Dellon ES. Systematic review: adrenal insufficiency secondary to swallowed topical corticosteroids in eosinophilic oesophagitis. Aliment Pharmacol Ther. 2018 Apr;47(8):1071-1078. doi: 10.1111/apt.14573. Epub 2018 Mar 5.
PMID: 29508432
responsible party type: Principal Investigator
investigator affiliation: Schneider Children's Medical Center, Israel
investigator full name: Noam Zevit
investigator title: Attending Pediatric Gastroenterologist
mesh term: Esophagitis
mesh term: Eosinophilic Esophagitis