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A Randomized Controlled Comparison of Esophageal Clearance Times of Oral Budesonide Preparations

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Abstract

Background

Topical steroids prepared as oral viscous slurries have become common in the treatment of eosinophilic esophagitis. Esophageal mucosal contact time correlates with clinical and histologic improvement.

Aim

To compare the mucosal contact time of alternative oral viscous budesonide (OVB) slurries with the conventional sucralose OVB.

Methods

A blinded randomized crossover trial investigating esophageal clearance of three OVB slurry preparations was done on healthy adults. Honey and xanthan gum OVB slurries were compared with standard sucralose OVB in 24 randomly assigned subjects. Each subject ingested the sucralose OVB and either the honey or xanthan gum OVB slurries. The esophageal clearance of each slurry was evaluated as an area under the curve (AUC) using 1 millicurie of technetium-99m-sulfur colloid (Tc99) co-administered in each OVB preparation using nuclear scintigraphy. A standardized taste survey was also administered.

Results

Xanthan gum had greater mucosal contact time compared to sucralose as measured by a higher AUC at 3 min (P = 0.002), while honey showed no significant difference in esophageal clearance relative to sucralose. Taste scores were significantly higher in the honey group, while scores for xanthan gum were no different from standard sucralose.

Conclusion

OVB slurries utilizing xanthan gum may be a superior alternative to a sucralose-based slurry due to its increased mucosal contact time and similar taste tolerance. Honey may be a suitable alternative as well, due to its similar contact time and favorable taste.

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Abbreviations

EoE:

Eosinophilic esophagitis

OVB:

Oral viscous budesonide

PPI:

Proton pump inhibitor

AUC:

Area under curve

References

  1. Rothenberg ME. Eosinophilic gastrointestinal disorders. J Allergy Clin Immunol. 2004;113:11–28.

    Article  PubMed  CAS  Google Scholar 

  2. Lieberman JA, Morotti RA, Konstantinou GN, et al. Dietary therapy can reverse esophageal subepithelial fibrosis in patients with eosinophilic esophagitis: a historical cohort. Allergy. 2012;67:1299.

    Article  PubMed  CAS  Google Scholar 

  3. Straumann A, Aceves SS, Blanchard C, et al. Pediatric and adult eosinophilic esophagitis: similarities and differences. Allergy. 2012;67:477–490.

    Article  PubMed  CAS  Google Scholar 

  4. Rothenberg ME. Biology and treatment of eosinophilic esophagitis. Gastroenterology. 2009;137:1238–1249.

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  5. Straumann A, Spichtin HP, Grize L, et al. Natural history of primary eosinophilic esophagitis: a follow-up of 30 adult patients for up to 11.5 years. Gastroenterology. 2003;125:1660–1669.

    Article  PubMed  Google Scholar 

  6. Markowitz JE, et al. Elemental diet is an effective treatment for eosinophilic esophagitis in children and adolescents. Am J Gastroenterol. 2003;98:777–782.

    Article  PubMed  CAS  Google Scholar 

  7. Dellon ES. Diagnosis and management of eosinophilic esophagitis. Clin Gastroenterol Hepatol. 2012;10:1066.

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  8. Liacouras CA, et al. Eosinophilic esophagitis: updated consensus recommendations for children and adults. J Allergy Clin Immunol. 2011;128:3–20.

    Article  PubMed  Google Scholar 

  9. Konikoff MR, Noel RJ, Blanchard C, et al. A randomized, double-blind, placebo-controlled trial of fluticasone propionate for pediatric eosinophilic esophagitis. Gastroenterology. 2006;131:1381–1391.

    Article  PubMed  CAS  Google Scholar 

  10. von Arnim U, Malfertheiner P. Eosinophilic esophagitis–treatment of eosinophilic esophagitis with drugs: corticosteroids. Dig Dis. 2014;32:126–129.

    Article  Google Scholar 

  11. Dohil R, Newbury R, Fox L, et al. Oral viscous budesonide is effective in children with eosinophilic esophagitis in a randomized, placebo-controlled trial. Gastroenterology. 2010;139:418–429.

    Article  PubMed  CAS  Google Scholar 

  12. Straumann A, Conus S, Degen L, et al. Budesonide is effective in adolescent and adult patients with active eosinophilic esophagitis. Gastroenterology. 2010;139:e1.

    Article  PubMed  CAS  Google Scholar 

  13. Dellon ES, Sheikh A, Speck O, et al. Viscous topical is more effective than nebulized steroid therapy for patients with eosinophilic esophagitis. Gastroenterology. 2012;143:321-4.e1.

    PubMed  Google Scholar 

  14. Aceves SS, Newbury RO, Chen D, et al. Resolution of remodeling in eosinophilic esophagitis correlates with epithelial response to topical corticosteroids. Allergy. 2010;65:109–116.

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  15. Aceves SS, Dohil R, Newbury RO, Bastian JF. Topical viscous budesonide suspension for treatment of eosinophilic esophagitis. J Allergy Clin Immunol. 2005;116:705–706.

    Article  PubMed  CAS  Google Scholar 

  16. Aceves SS, Bastian JF, Newbury RO, et al. Oral viscous budesonide: a potential new therapy for eosinophilic esophagitis in children. Am J Gastroenterol. 2007;102:2271.

    Article  PubMed  CAS  Google Scholar 

  17. Liacouras CA, et al. Eosinophilic esophagitis: updated consensus recommendations for children and adults. J Allergy Clin Immunol. 2011;128:3–20.

    Article  PubMed  Google Scholar 

  18. Brown RJ, Rother KI. Non-nutritive sweeteners and their role in the gastrointestinal tract. J Clin Endocrinol Metab. 2012;97:2597–2605.

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  19. Abou-Donia MB, El-Masry EM, Abdel-Rahman AA, McLendon RE, Schiffman SS. Splenda alters gut microflora and increases intestinal p-glycoprotein and cytochrome p-450 in male rats. J Toxicol Environ Health A. 2008;71:1415–1429.

    Article  PubMed  CAS  Google Scholar 

  20. Konikoff MR, et al. Potential of blood eosinophils, eosinophil-derived neurotoxin, and eotaxin-3 as biomarkers of eosinophilic esophagitis. Clin Gastroenterol Hepatol. 2006;4:1328–1336.

    Article  PubMed  CAS  Google Scholar 

  21. Bartoshuk LM. The sensory aspects of swallowing: What do we know?. Atlanta, GA: Symposium presentation at the Annual Convention of the American Speech-Language-Hearing Association; 2012.

    Google Scholar 

  22. Bartoshuk LM, Duffy VB, Green BG, et al. Valid across-group comparisons with labeled scales: the gLMS versus magnitude matching. Physiol Behav. 2004;82:109–114.

    Article  PubMed  CAS  Google Scholar 

  23. Bartoshuk LM, Snyder DJ, Duffy VB. Hedonic gLMS: valid comparisons for food liking/disliking across obesity, age, sex and PROP status. Chem Senses. 2006;31:A50.

    Google Scholar 

  24. Green BG, Dalton P, Coward B, Shaffer G, Rankin K, Higgins J. Evaluating the ‘labeled magnitude scale’ for measuring sensations of taste and smell. Chem Senses. 1996;18:323–334.

    Article  Google Scholar 

  25. Kalva J (2009) Comparison of the hedonic general labeled magnitude scale to the hedonic 9-point scale. Unpublished thesis, University of Florida.

  26. Lim J, Wood A, Green BG. Derivation and evaluation of a labeled hedonic scale. Chem Senses. 2009;43:739–751.

    Article  Google Scholar 

  27. http://www.nihtoolbox.org/WhatAndWhy/Sensation/Taste/Pages/NIH-Toolbox-Regional-Taste-Intensity-Test.aspx

  28. Tudor G, Koch GG. Review of nonparametric methods for the analysis of crossover studies. Stat Methods Med Res. 1994;3:345.

    Article  PubMed  CAS  Google Scholar 

  29. FDA CFR Title 21, Vol 3, Part 172, subpart G, section 172.695

  30. Beal J, Silverman B, Bellant J, et al. Late onset necrotizing enterocolitis in infants following use of a xanthan gum-containing thickening agent. J Pediatr. 2012;161:354–356.

    Article  PubMed  Google Scholar 

  31. http://www.fda.gov/ForConsumers/ConsumerUpdates/ucm256250.htm

  32. Ivanoska V, Rademaker CM, van Dijk L, Mantel-Teeuwisse AK. Pediatric drug formulations: a review of challenges and progress. Pediatrics. 2014;134:361–372.

    Article  Google Scholar 

  33. Liu F, Ranmal S, Batchelor HK, et al. Patient-centred pharmaceutical design to improve acceptability of medicines: similarities and differences in paediatric and geriatric populations. Drugs. 2014;74:1871–1889.

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  34. van Rhijn BD, Oors JM, Smout AJ, Bredenoord AJ. Prevalence of esophageal motility abnormalities increases with longer disease duration in adult patients with eosinophilic esophagitis. Neurogastroenterol Motil. 2014;26:1349–1355.

    Article  PubMed  Google Scholar 

  35. Hirano I, Aceves SS. Clinical implications and pathogenesis of esophageal remodeling in eosinophilic esophagitis. Gastroenterol Clin North Am. 2014;43:297–316.

    Article  PubMed  PubMed Central  Google Scholar 

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Acknowledgments

The authors would like to thank Drs. Phil Rogers, Michael McCown, and Eiping Quang for their contributions and guidance.

Funding source

Henry Jackson Foundation provided financial support for this study.

Author contributions

Jody N. Hefner, DO, contributed to the study concept and design and Institutional Review Board protocol submission and revision, obtained funding, recruited/consented to subjects, and was involved in acquisition, analysis, and interpretation of data, and drafting of the initial manuscript, editing the manuscript, and approval of the final manuscript. Robin S. Howard, MA, assisted with study design, statistical analysis, organization and interpretation of data, and manuscript revision. Robert Massey was involved in the study design, study implementation, and administrative and technical support. Miland Valencia contributed to the study implementation, and administrative and technical support. Derek J. Stocker, MD, was involved in the study concept and design, IRB submission and approval, and data and imaging processing. Katherine Q. Philla, MD, contributed to the study concept and design, IRB revisions, administrative and technical support, and the manuscript revision. Matthew D. Goldman, MD, contributed to the study concept and design, manuscript revision, and administrative support. Cade M. Nylund, MD, was involved in interpretation of data, manuscript revision, study supervision, and material support. Steve B. Min, MD, contributed to the study concept and design, critical revision of the manuscript, administrative and technical support, study supervision, approval of the final manuscript, and also assisted with Institutional Review Board submission and revisions.

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Authors and Affiliations

  1. Department of Pediatrics, Walter Reed National Military Medical Center, Bethesda, MD, USA

    Jody N. Hefner, Katherine Q. Philla, Matthew D. Goldman, Cade M. Nylund & Steve B. Min

  2. Department of Pediatrics, Uniformed Services University of the Health Sciences, Bethesda, MD, USA

    Jody N. Hefner, Katherine Q. Philla, Matthew D. Goldman, Cade M. Nylund & Steve B. Min

  3. Department of Research Programs, Walter Reed National Military Medical Center, Bethesda, MD, USA

    Robin S. Howard

  4. Department of Nuclear Medicine, Walter Reed National Military Medical Center, Bethesda, MD, USA

    Robert Massey, Miland Valencia & Derek J. Stocker

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  1. Jody N. Hefner
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Correspondence to Jody N. Hefner.

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The views expressed in this article are those of the authors and do not reflect the official policy or position of the United States Army, United States Air Force, United States Navy, the Department of Defense, or the US Government. Title 17 USC 105 provides that “copyright protection under this title is not available for any work of the United States Government.” Title 17 USC 101 defines a United States government work as “a work prepared by a military service member or employee of the United States government as part of that person’s official duties.” This work was prepared as part of our official duties.

https://clinicaltrials.gov/ct2/show/NCT02125851 (NCT02125851).

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Hefner, J.N., Howard, R.S., Massey, R. et al. A Randomized Controlled Comparison of Esophageal Clearance Times of Oral Budesonide Preparations. Dig Dis Sci 61, 1582–1590 (2016). https://doi.org/10.1007/s10620-015-3990-4

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