EoE RCT Fluticasone and Omeprazole vs Fluticasone Alone

NCT03781596 | Unknown Phase 4 DMC FDA Drug

• 1 other identifier: WRNMMC-2018-0133
• Study Type: interventional
• Target: 100
• Locations: 1 country
• Sites: 1

Brief Summary

The purpose of this study is to evaluate the efficacy of combination therapy with omeprazole and swallowed fluticasone vs fluticasone therapy and placebo in the treatment of Eosinophilic Esophagitis (EoE) in children and adults. This study will be a double-blinded, randomized controlled trial. The primary outcome measured will be histologic assessment of esophageal tissue biopsies measuring number of eosinophils per high power field (eos/hpf). Secondary outcomes will be endoscopic findings and symptomatic changes following therapy using validated endoscopic scoring measures and participant surveys, respectively.

Conditions

Eosinophilic Esophagitis

Outcome Measures

Primary Outcomes (1)

• Change in esophageal eosinophilia

  The number of eosinophils per high powered field will be counted by participating pathologist.

  There will be one at week 0 and week 8.

Secondary Outcomes (2)

• Change in Endoscopic Reference Score

  This will be done at week 0 and week 8

• Change in Symptom Scoring

  Week 0 and week 8

Study Arms (2)

Fluticasone and omeprazole

EXPERIMENTAL

These patients will be prescribed swallowed fluticasone and omeprazole to be taken together for the 8 week period. Dosing will be based on weight and age. Primary outcome measure will be the change in esophageal biopsy histology, or number of eosinophils per high powered field, from week 0 to week 8. Secondary outcomes will include changes in the following variables between week 0 and 8: eotaxin staining of the esophageal biopsy tissue, endoscopic scoring from photos of the esophagus obtained during endoscopy, and symptom scoring based on surveys.

Diagnostic Test: Retrospective evaluation of endoscopy prior to study drug; Other: Symptom Survey; Other: Medication Compliance Phone Call; Diagnostic Test: Endoscopy while on study drug; Drug: Fluticasone; Drug: Omeprazole

Fluticasone and placebo

PLACEBO COMPARATOR

These patients will be prescribed swallowed fluticasone and a placebo medication that appears identical to omeprazole to be taken together for an 8 week period. Dosing will be based on weight and age. Primary outcome measure will be the change in esophageal biopsy histology, or number of eosinophils per high powered field, from week 0 to week 8. Secondary outcomes will include changes in the following variables between week 0 and 8: eotaxin staining of the esophageal biopsy tissue, endoscopic scoring from photos of the esophagus obtained during endoscopy, and symptom scoring based on surveys.

Diagnostic Test: Retrospective evaluation of endoscopy prior to study drug; Other: Symptom Survey; Other: Medication Compliance Phone Call; Diagnostic Test: Endoscopy while on study drug; Drug: Fluticasone; Drug: Placebo oral capsule

Interventions

Retrospective evaluation of endoscopy prior to study drug DIAGNOSTIC_TEST

Once enrolled, the patient's original endoscopy will be evaluated including the images from the EGD and the biopsies for eotaxin 3 staining and eosinophilic burden.

Fluticasone and omeprazole; Fluticasone and placebo

Symptom Survey OTHER

Patient will complete symptom survey prior to starting the study drugs.

Fluticasone and omeprazole; Fluticasone and placebo

Medication Compliance Phone Call OTHER

The patient will receive a phone call at 4 weeks to evaluate medication compliance including the number on the inhaler and the number of pills remaining in the container.

Fluticasone and omeprazole; Fluticasone and placebo

Endoscopy while on study drug DIAGNOSTIC_TEST

Endoscopy will be performed after 8 weeks of therapy. Endoscopic scoring will be assigned and the histology will be evaluated, including eotaxin 3 staining. The change in eosinophil count and eotaxin staining will be measured.

Fluticasone and omeprazole; Fluticasone and placebo

Fluticasone DRUG

Participants in the experimental and placebo arms will be given swallowed fluticasone for an 8 week course. Doses determined by age and weight.

Fluticasone and omeprazole; Fluticasone and placebo

Omeprazole DRUG

The participants in the experimental arm will be given oral omprazole capsules for an 8 week period (along with the swallowed fluticasone). Doses determined by age and weight.

Fluticasone and omeprazole

Placebo oral capsule DRUG

The participants in the placebo arm will be given placebo capsules for an 8 week period (along with the swallowed fluticasone). Number of pills determined by age and weight (to match omeprazole dosing).

Fluticasone and placebo

Eligibility Criteria

• Age: 6 Years - 60 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Child (0-17), Adult (18-64)

You may qualify if:

• age 6 to 60 years old
• DEERS (defense enrollment eligibility reporting system) eligible
• diagnosis of eosinophilic esophagitis

You may not qualify if:

• Outside of age range
• Co-existing inflammatory gastroenterologic condition such as celiac disease, eosinophilic esophagitis, or inflammatory bowel disease.
• Concurrent use of oral steroids
• Pregnancy
• Refusal to undergo endoscopy

Sponsors & Collaborators

• Claire Daniels: lead

Study Sites (1)

Walter Reed National Military Medical Center

Bethesda, Maryland, 20889, United States

RECRUITING

Related Publications (19)

• Liacouras CA, Furuta GT, Hirano I, Atkins D, Attwood SE, Bonis PA, Burks AW, Chehade M, Collins MH, Dellon ES, Dohil R, Falk GW, Gonsalves N, Gupta SK, Katzka DA, Lucendo AJ, Markowitz JE, Noel RJ, Odze RD, Putnam PE, Richter JE, Romero Y, Ruchelli E, Sampson HA, Schoepfer A, Shaheen NJ, Sicherer SH, Spechler S, Spergel JM, Straumann A, Wershil BK, Rothenberg ME, Aceves SS. Eosinophilic esophagitis: updated consensus recommendations for children and adults. J Allergy Clin Immunol. 2011 Jul;128(1):3-20.e6; quiz 21-2. doi: 10.1016/j.jaci.2011.02.040. Epub 2011 Apr 7.

  PMID: 21477849 BACKGROUND

• Dellon ES, Jensen ET, Martin CF, Shaheen NJ, Kappelman MD. Prevalence of eosinophilic esophagitis in the United States. Clin Gastroenterol Hepatol. 2014 Apr;12(4):589-96.e1. doi: 10.1016/j.cgh.2013.09.008. Epub 2013 Sep 11.

  PMID: 24035773 BACKGROUND

• Liacouras CA, Wenner WJ, Brown K, Ruchelli E. Primary eosinophilic esophagitis in children: successful treatment with oral corticosteroids. J Pediatr Gastroenterol Nutr. 1998 Apr;26(4):380-5. doi: 10.1097/00005176-199804000-00004.

  PMID: 9552132 BACKGROUND

• Schaefer ET, Fitzgerald JF, Molleston JP, Croffie JM, Pfefferkorn MD, Corkins MR, Lim JD, Steiner SJ, Gupta SK. Comparison of oral prednisone and topical fluticasone in the treatment of eosinophilic esophagitis: a randomized trial in children. Clin Gastroenterol Hepatol. 2008 Feb;6(2):165-73. doi: 10.1016/j.cgh.2007.11.008.

  PMID: 18237866 BACKGROUND

• Papadopoulou A, Dias JA. Eosinophilic esophagitis: an emerging disease in childhood - review of diagnostic and management strategies. Front Pediatr. 2014 Nov 21;2:129. doi: 10.3389/fped.2014.00129. eCollection 2014.

  PMID: 25485261 BACKGROUND

• Konikoff MR, Noel RJ, Blanchard C, Kirby C, Jameson SC, Buckmeier BK, Akers R, Cohen MB, Collins MH, Assa'ad AH, Aceves SS, Putnam PE, Rothenberg ME. A randomized, double-blind, placebo-controlled trial of fluticasone propionate for pediatric eosinophilic esophagitis. Gastroenterology. 2006 Nov;131(5):1381-91. doi: 10.1053/j.gastro.2006.08.033. Epub 2006 Aug 16.

  PMID: 17101314 BACKGROUND

• Dohil R, Newbury R, Fox L, Bastian J, Aceves S. Oral viscous budesonide is effective in children with eosinophilic esophagitis in a randomized, placebo-controlled trial. Gastroenterology. 2010 Aug;139(2):418-29. doi: 10.1053/j.gastro.2010.05.001. Epub 2010 May 7.

  PMID: 20457157 BACKGROUND

• Butz BK, Wen T, Gleich GJ, Furuta GT, Spergel J, King E, Kramer RE, Collins MH, Stucke E, Mangeot C, Jackson WD, O'Gorman M, Abonia JP, Pentiuk S, Putnam PE, Rothenberg ME. Efficacy, dose reduction, and resistance to high-dose fluticasone in patients with eosinophilic esophagitis. Gastroenterology. 2014 Aug;147(2):324-33.e5. doi: 10.1053/j.gastro.2014.04.019. Epub 2014 Apr 22.

  PMID: 24768678 BACKGROUND

• Alexander JA, Jung KW, Arora AS, Enders F, Katzka DA, Kephardt GM, Kita H, Kryzer LA, Romero Y, Smyrk TC, Talley NJ. Swallowed fluticasone improves histologic but not symptomatic response of adults with eosinophilic esophagitis. Clin Gastroenterol Hepatol. 2012 Jul;10(7):742-749.e1. doi: 10.1016/j.cgh.2012.03.018. Epub 2012 Apr 1.

  PMID: 22475741 BACKGROUND

• Asher Wolf W, Dellon ES. Eosinophilic esophagitis and proton pump inhibitors: controversies and implications for clinical practice. Gastroenterol Hepatol (N Y). 2014 Jul;10(7):427-32.

  PMID: 25904830 BACKGROUND

• Moawad FJ, Veerappan GR, Dias JA, Baker TP, Maydonovitch CL, Wong RK. Randomized controlled trial comparing aerosolized swallowed fluticasone to esomeprazole for esophageal eosinophilia. Am J Gastroenterol. 2013 Mar;108(3):366-72. doi: 10.1038/ajg.2012.443. Epub 2013 Feb 12.

  PMID: 23399553 BACKGROUND

• Bullock JZ, Villanueva JM, Blanchard C, Filipovich AH, Putnam PE, Collins MH, Risma KA, Akers RM, Kirby CL, Buckmeier BK, Assa'ad AH, Hogan SP, Rothenberg ME. Interplay of adaptive th2 immunity with eotaxin-3/c-C chemokine receptor 3 in eosinophilic esophagitis. J Pediatr Gastroenterol Nutr. 2007 Jul;45(1):22-31. doi: 10.1097/MPG.0b013e318043c097.

  PMID: 17592361 BACKGROUND

• Blanchard C, Mingler MK, Vicario M, Abonia JP, Wu YY, Lu TX, Collins MH, Putnam PE, Wells SI, Rothenberg ME. IL-13 involvement in eosinophilic esophagitis: transcriptome analysis and reversibility with glucocorticoids. J Allergy Clin Immunol. 2007 Dec;120(6):1292-300. doi: 10.1016/j.jaci.2007.10.024.

  PMID: 18073124 BACKGROUND

• Park JY, Zhang X, Nguyen N, Souza RF, Spechler SJ, Cheng E. Proton pump inhibitors decrease eotaxin-3 expression in the proximal esophagus of children with esophageal eosinophilia. PLoS One. 2014 Jul 2;9(7):e101391. doi: 10.1371/journal.pone.0101391. eCollection 2014.

  PMID: 24988451 BACKGROUND

• Zhang X, Huo X, Yu C, Zhang Q, Nadatani Y, Tamagawa Y, et al. Omeprazole and fluticasone inhibit IL-13-stimulated eotaxin-3 expression by esophageal epithelial cells through different mechanisms and with additive effects: Rationale for combining PPIs with topical steroids for EoE patients. Gastroenterology 2015;148(4, Supplement 1):S-51.

  BACKGROUND

• 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 BACKGROUND

• Papadopoulou A, Koletzko S, Heuschkel R, Dias JA, Allen KJ, Murch SH, Chong S, Gottrand F, Husby S, Lionetti P, Mearin ML, Ruemmele FM, Schappi MG, Staiano A, Wilschanski M, Vandenplas Y; ESPGHAN Eosinophilic Esophagitis Working Group and the Gastroenterology Committee. Management guidelines of eosinophilic esophagitis in childhood. J Pediatr Gastroenterol Nutr. 2014 Jan;58(1):107-18. doi: 10.1097/MPG.0b013e3182a80be1.

  PMID: 24378521 BACKGROUND

• Dellon ES, Cotton CC, Gebhart JH, Higgins LL, Beitia R, Woosley JT, Shaheen NJ. Accuracy of the Eosinophilic Esophagitis Endoscopic Reference Score in Diagnosis and Determining Response to Treatment. Clin Gastroenterol Hepatol. 2016 Jan;14(1):31-9. doi: 10.1016/j.cgh.2015.08.040. Epub 2015 Sep 25.

  PMID: 26404868 BACKGROUND

• Hirano I, Moy N, Heckman MG, Thomas CS, Gonsalves N, Achem SR. Endoscopic assessment of the oesophageal features of eosinophilic oesophagitis: validation of a novel classification and grading system. Gut. 2013 Apr;62(4):489-95. doi: 10.1136/gutjnl-2011-301817. Epub 2012 May 22.

  PMID: 22619364 BACKGROUND

MeSH Terms

Conditions

Eosinophilic Esophagitis

Interventions

Fluticasone; Omeprazole

Condition Hierarchy (Ancestors)

Esophagitis; Esophageal Diseases; Gastrointestinal Diseases; Digestive System Diseases; Gastroenteritis; Eosinophilia; Leukocyte Disorders; Hematologic Diseases; Hemic and Lymphatic Diseases; Hypersensitivity, Immediate; Hypersensitivity; Immune System Diseases

Intervention Hierarchy (Ancestors)

Androstadienes; Androstenes; Androstanes; Steroids; Fused-Ring Compounds; Polycyclic Compounds; 2-Pyridinylmethylsulfinylbenzimidazoles; Sulfoxides; Sulfur Compounds; Organic Chemicals; Pyridines; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds; Benzimidazoles; Heterocyclic Compounds, 2-Ring; Heterocyclic Compounds, Fused-Ring

Central Study Contacts

Steve B Min, M.D.

CONTACT

301-295-4959; steve.b.min.mil@mail.mil

Claire P Daniels, M.D.

CONTACT

301-295-4959; claire.p.daniels.mil@mail.mil

Study Design

• Study Type: interventional
• Phase: phase 4
• Allocation: RANDOMIZED
• Masking: QUADRUPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR, OUTCOMES ASSESSOR
• Purpose: OTHER
• Intervention Model: PARALLEL
• Sponsor Type: FED
• Responsible Party: SPONSOR INVESTIGATOR
• PI Title: Associate Investigator

Study Record Dates

• First Submitted: November 11, 2018
• First Posted: December 20, 2018
• Study Start: October 2, 2018
• Primary Completion: October 2, 2020
• Study Completion: October 2, 2022
• Last Updated: December 20, 2018

Record last verified: 2018-12

Data Sharing

• IPD Sharing: Will not share

Locations

US (1)