A Trial of Montelukast for Maintenance Therapy of Eosinophilic Esophagitis in Children

Summary

Eosinophilic Esophagitis (EE) is a condition where eosinophils (a cell that fights infection) travel to the esophagus (the tube through which food passes to the stomach). These cells do not belong there and can cause pain, soreness, difficulty swallowing and sometimes vomiting. Ways to treat this condition include medicine, not eating some foods, and drinking a specific formula (like milk) without eating any other foods. Doing these things can help fight off EE but these problems can come back when treatment is stopped. If EE symptoms go on for a long time, it can lead to the esophagus becoming narrow and feeling tight when eating and swallowing and surgery may be needed to widen the narrowed area to relieve the sensation of tightening. Montelukast is a medicine that fights off a type of chemical that can be a magnet for eosinophils. People usually take this medicine to help treat their asthma. It is not approved to treat EE. This medication is taken once a day. The purpose of this study is to see if Montelukast, compared to placebo, will help reduce the number of eosinophils in children with EE and help stop the tightening of the esophagus.

Timeline

Start

2011-12

Primary completion

2015-02

Completion

2015-02

Publications

• Background 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.
• Background Rothenberg ME. Biology and treatment of eosinophilic esophagitis. Gastroenterology. 2009 Oct;137(4):1238-49. doi: 10.1053/j.gastro.2009.07.007. Epub 2009 Aug 15.
• 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.
• 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.
• 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.
• Background Markowitz JE, Spergel JM, Ruchelli E, Liacouras CA. Elemental diet is an effective treatment for eosinophilic esophagitis in children and adolescents. Am J Gastroenterol. 2003 Apr;98(4):777-82. doi: 10.1111/j.1572-0241.2003.07390.x.
• Background Assa'ad AH, Putnam PE, Collins MH, Akers RM, Jameson SC, Kirby CL, Buckmeier BK, Bullock JZ, Collier AR, Konikoff MR, Noel RJ, Guajardo JR, Rothenberg ME. Pediatric patients with eosinophilic esophagitis: an 8-year follow-up. J Allergy Clin Immunol. 2007 Mar;119(3):731-8. doi: 10.1016/j.jaci.2006.10.044. Epub 2007 Jan 25.
• Background Blanchard C, Wang N, Rothenberg ME. Eosinophilic esophagitis: pathogenesis, genetics, and therapy. J Allergy Clin Immunol. 2006 Nov;118(5):1054-9. doi: 10.1016/j.jaci.2006.07.038. Epub 2006 Sep 18.
• Background Blanchard C, Rothenberg ME. Basic pathogenesis of eosinophilic esophagitis. Gastrointest Endosc Clin N Am. 2008 Jan;18(1):133-43; x. doi: 10.1016/j.giec.2007.09.016.
• Background Chehade M, Sampson HA, Morotti RA, Magid MS. Esophageal subepithelial fibrosis in children with eosinophilic esophagitis. J Pediatr Gastroenterol Nutr. 2007 Sep;45(3):319-28. doi: 10.1097/MPG.0b013e31806ab384.
• Background Aceves SS, Ackerman SJ. Relationships between eosinophilic inflammation, tissue remodeling, and fibrosis in eosinophilic esophagitis. Immunol Allergy Clin North Am. 2009 Feb;29(1):197-211, xiii-xiv. doi: 10.1016/j.iac.2008.10.003.
• Background Wershil BK. Exploring the role of mast cells in eosinophilic esophagitis. Immunol Allergy Clin North Am. 2009 Feb;29(1):189-95, xiii. doi: 10.1016/j.iac.2008.09.006.
• Background Lucendo AJ, Bellon T, Lucendo B. The role of mast cells in eosinophilic esophagitis. Pediatr Allergy Immunol. 2009 Sep;20(6):512-8. doi: 10.1111/j.1399-3038.2008.00798.x. Epub 2008 Aug 4.
• Background Attwood SE, Lewis CJ, Bronder CS, Morris CD, Armstrong GR, Whittam J. Eosinophilic oesophagitis: a novel treatment using Montelukast. Gut. 2003 Feb;52(2):181-5. doi: 10.1136/gut.52.2.181.
• Background El-Swefy S, Hassanen SI. Improvement of hepatic fibrosis by leukotriene inhibition in cholestatic rats. Ann Hepatol. 2009 Jan-Mar;8(1):41-9.
• Background Izumo T, Kondo M, Nagai A. Cysteinyl-leukotriene 1 receptor antagonist attenuates bleomycin-induced pulmonary fibrosis in mice. Life Sci. 2007 Apr 24;80(20):1882-6. doi: 10.1016/j.lfs.2007.02.038. Epub 2007 Mar 12.
• Background Montagna NA, de Oliveira ML, Mandarim-de-Lacerda CA, Chimelli L. Leprosy: contribution of mast cells to epineurial collagenization. Clin Neuropathol. 2005 Nov-Dec;24(6):284-90.

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Indications