Proton Pump Inhibitor (PPI) Response in Eosinophilic Esophagitis Assessed by Transnasal Endoscopy (TNE)

NCT04149470 | Active Not Recruiting Phase 4 FDA Drug

• 1 other identifier: 19-1119
• Study Type: interventional
• Target: 90
• Locations: 1 country
• Sites: 1

Brief Summary

This study will enroll participants who have been diagnosed with Eosinophilic Esophagitis (EoE). Upon study enrollment, the participant will begin a proton pump inhibitor (PPI), Omeprazole 20mg twice daily. After taking Omeprazole for four weeks, the participant will have a Transnasal Endoscopy, and biopsies will be taken to determine the histological change. If the biopsies are abnormal, the participant continues Omeprazole and will undergo another endoscopy at eight weeks. The study aims to determine the percentage of children with Eosinophilic Esophagitis who improve with PPI use and to determine the length of time and effectiveness of PPI therapy in the management of EoE. The investigators hypothesize that following the initiation of PPI for treatment of Eosinophilic Esophagitis, biopsies obtained will show decreasing eosinophil counts at four weeks, which is sooner than the previously reported eight-week period.

Conditions

Eosinophilic Esophagitis

Keywords

EoE; PPI; Proton Pump Inhibitor; Omeprazole; eosinophil; TNE; Transnasal Endoscopy; Esophageal Diseases; Esophagitis; Gastrointestinal Diseases; Eosinophilia; Gastroenteritis; Eosinophilic Oesophagitis; Transnasal Esophagogastroduodenoscopy; Transnasal Esophagoscopy

Outcome Measures

Primary Outcomes (3)

• Histological Response at baseline

  The histological response will be based on pathologist's review of esophageal biopsies for pediatric participants with Eosinophilic Esophagitis (EoE). EoE diagnosis is identified if there are ≥ 15 eosinophils per high power field (hpf) in the esophagus.

  baseline

• Change in Histological Response Rate at four weeks

  The histological response will be based on pathologist's review of esophageal biopsies for pediatric participants with Eosinophilic Esophagitis (EoE) who are prescribed a high dose proton pump inhibitor, Omeprazole 20 mg twice daily. Biopsies will be evaluated using the EoE histological scoring system. Response will be defined as the peak eosinophil count of \< 15 eosinophils per high power field and normal will be defined at 0 eosinophils per high power field.

  4 weeks

• Change in Histological Response Rate at eight weeks

  The histological response will be based on pathologist's review of esophageal biopsies for pediatric participants with Eosinophilic Esophagitis (EoE) who are prescribed a high dose proton pump inhibitor, Omeprazole 20 mg twice daily. Biopsies will be evaluated using the EoE histological scoring system. Response will be defined as the peak eosinophil count of \< 15 eosinophils per high power field and normal will be defined at 0 eosinophils per high power field.

  8 weeks

Secondary Outcomes (6)

• PEESS (Pediatric Eosinophilic Esophagitis Symptom Severity Module) scores at enrollment

  At enrollment

• PEESS (Pediatric Eosinophilic Esophagitis Symptom Severity Module) scores at four weeks

  4 weeks

• PEESS (Pediatric Eosinophilic Esophagitis Symptom Severity Module) scores at eight weeks

  8 weeks

• Eosinophilic Esophagitis Histology Scoring System (HSS) scores at enrollment

  At enrollment

• Eosinophilic Esophagitis Histology Scoring System (HSS) scores at four weeks

  4 weeks

Study Arms (1)

Omeprazole

EXPERIMENTAL

Participants will receive high dose PPI therapy (Omeprazole 20mg twice daily) and will be evaluated for histological improvement.

Drug: Omeprazole 20mg BID

Interventions

Omeprazole 20mg BID DRUG

High dose PPI therapy (Omeprazole 20mg twice daily)

Omeprazole

Eligibility Criteria

• Age: 8 Years - 22 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Child (0-17), Adult (18-64)

You may qualify if:

• Provide signed and dated informed consent form
• Male or female, ages 8-22
• Current diagnosis of Eosinophilic Esophagitis (≥ 15 eos/HPF) within the last 6 months
• Able to swallow pills or open capsule to take medication with apple sauce
• Weight \>20kg
• Willing to undergo unsedated transnasal endoscopy (TNE)

You may not qualify if:

• Inability or unwillingness of participant to give written informed consent or comply with study protocol.
• Have a known bleeding disorder
• Current topical esophageal corticosteroid or systemic steroid treatment within past 8 weeks
• No therapy with H2 therapy within the past 16 weeks
• Planned or anticipated change in the diet during the study duration.
• Planned or anticipated change in other corticosteroid medications
• Uncontrolled cough, rhinorrhea, rhinitis obstructing nasal passages, GI illness or determination of significant illness at screening
• Pregnancy, breast feeding or plans to become pregnant
• Use of investigational drug within last 16 weeks
• Allergy to any medications used for procedures
• Allergy to PPI
• Past or current medical problems or findings from physical exam or laboratory testing that are not listed above, which, in the opinion of the investigator, may pose additional risks from participation in the study, may interfere with participant's ability to comply with study requirements, or that may impact the quality or interpretation of the data obtained from the study

Sponsors & Collaborators

• University of Colorado, Denver: lead
• Children's Hospital Colorado: collaborator

Study Sites (1)

Children's Hospital Colorado

Aurora, Colorado, 80045, United States

Location

Related Publications (12)

• 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.

  PMID: 17919504 RESULT

• Friedlander JA, DeBoer EM, Soden JS, Furuta GT, Menard-Katcher CD, Atkins D, Fleischer DM, Kramer RE, Deterding RR, Capocelli KE, Prager JD. Unsedated transnasal esophagoscopy for monitoring therapy in pediatric eosinophilic esophagitis. Gastrointest Endosc. 2016 Feb;83(2):299-306.e1. doi: 10.1016/j.gie.2015.05.044. Epub 2015 Jul 2.

  PMID: 26142551 RESULT

• Nguyen N, Lavery WJ, Capocelli KE, Smith C, DeBoer EM, Deterding R, Prager JD, Leinwand K, Kobak GE, Kramer RE, Menard-Katcher C, Furuta GT, Atkins D, Fleischer D, Greenhawt M, Friedlander JA. Transnasal Endoscopy in Unsedated Children With Eosinophilic Esophagitis Using Virtual Reality Video Goggles. Clin Gastroenterol Hepatol. 2019 Nov;17(12):2455-2462. doi: 10.1016/j.cgh.2019.01.023. Epub 2019 Jan 29.

  PMID: 30708107 RESULT

• Dellon ES, Gonsalves N, Hirano I, Furuta GT, Liacouras CA, Katzka DA; American College of Gastroenterology. ACG clinical guideline: Evidenced based approach to the diagnosis and management of esophageal eosinophilia and eosinophilic esophagitis (EoE). Am J Gastroenterol. 2013 May;108(5):679-92; quiz 693. doi: 10.1038/ajg.2013.71. Epub 2013 Apr 9.

  PMID: 23567357 RESULT

• Molina-Infante J, Ferrando-Lamana L, Ripoll C, Hernandez-Alonso M, Mateos JM, Fernandez-Bermejo M, Duenas C, Fernandez-Gonzalez N, Quintana EM, Gonzalez-Nunez MA. Esophageal eosinophilic infiltration responds to proton pump inhibition in most adults. Clin Gastroenterol Hepatol. 2011 Feb;9(2):110-7. doi: 10.1016/j.cgh.2010.09.019. Epub 2010 Oct 1.

  PMID: 20920599 RESULT

• Molina-Infante J, Bredenoord AJ, Cheng E, Dellon ES, Furuta GT, Gupta SK, Hirano I, Katzka DA, Moawad FJ, Rothenberg ME, Schoepfer A, Spechler SJ, Wen T, Straumann A, Lucendo AJ; PPI-REE Task Force of the European Society of Eosinophilic Oesophagitis (EUREOS). Proton pump inhibitor-responsive oesophageal eosinophilia: an entity challenging current diagnostic criteria for eosinophilic oesophagitis. Gut. 2016 Mar;65(3):524-31. doi: 10.1136/gutjnl-2015-310991. Epub 2015 Dec 18.

  PMID: 26685124 RESULT

• 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 RESULT

• Gutierrez-Junquera C, Fernandez-Fernandez S, Cilleruelo ML, Rayo A, Echeverria L, Quevedo S, Bracamonte T, Roman E. High Prevalence of Response to Proton-pump Inhibitor Treatment in Children With Esophageal Eosinophilia. J Pediatr Gastroenterol Nutr. 2016 May;62(5):704-10. doi: 10.1097/MPG.0000000000001019.

  PMID: 26513622 RESULT

• Lucendo AJ, Arias A, Molina-Infante J. Efficacy of Proton Pump Inhibitor Drugs for Inducing Clinical and Histologic Remission in Patients With Symptomatic Esophageal Eosinophilia: A Systematic Review and Meta-Analysis. Clin Gastroenterol Hepatol. 2016 Jan;14(1):13-22.e1. doi: 10.1016/j.cgh.2015.07.041. Epub 2015 Aug 3.

  PMID: 26247167 RESULT

• Philpott H, Nandurkar S, Royce SG, Gibson PR. Ultrathin unsedated transnasal gastroscopy in monitoring eosinophilic esophagitis. J Gastroenterol Hepatol. 2016 Mar;31(3):590-4. doi: 10.1111/jgh.13173.

  PMID: 26426817 RESULT

• Dumortier J, Ponchon T, Scoazec JY, Moulinier B, Zarka F, Paliard P, Lambert R. Prospective evaluation of transnasal esophagogastroduodenoscopy: feasibility and study on performance and tolerance. Gastrointest Endosc. 1999 Mar;49(3 Pt 1):285-91. doi: 10.1016/s0016-5107(99)70002-7.

  PMID: 10049409 RESULT

• Yagi J, Adachi K, Arima N, Tanaka S, Ose T, Azumi T, Sasaki H, Sato M, Kinoshita Y. A prospective randomized comparative study on the safety and tolerability of transnasal esophagogastroduodenoscopy. Endoscopy. 2005 Dec;37(12):1226-31. doi: 10.1055/s-2005-921037.

  PMID: 16329022 RESULT

MeSH Terms

Conditions

Eosinophilic Esophagitis; Esophageal Diseases; Esophagitis; Gastrointestinal Diseases; Eosinophilia; Gastroenteritis

Interventions

Omeprazole; BID protein, human

Condition Hierarchy (Ancestors)

Digestive System Diseases; Leukocyte Disorders; Hematologic Diseases; Hemic and Lymphatic Diseases; Hypersensitivity, Immediate; Hypersensitivity; Immune System Diseases

Intervention Hierarchy (Ancestors)

2-Pyridinylmethylsulfinylbenzimidazoles; Sulfoxides; Sulfur Compounds; Organic Chemicals; Pyridines; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds; Benzimidazoles; Heterocyclic Compounds, 2-Ring; Heterocyclic Compounds, Fused-Ring

Study Officials

• Nathalie Nguyen, MD

  Children's Hospital Colorado

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 4
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: October 30, 2019
• First Posted: November 4, 2019
• Study Start: October 7, 2020
• Primary Completion: August 1, 2024
• Study Completion: August 1, 2024
• Last Updated: July 3, 2024

Record last verified: 2024-07

Data Sharing

• IPD Sharing: Will not share

Locations

US (1)