Effect of Dupilumab on the Muscle Function of the Esophagus (food Pipe) in Participants with Eosinophilic Esophagitis (EoE)

Summary

The goal of this study is to research Dupilumab, an FDA approved medication in treating patients diagnosed with Eosinophilic esophagitis (EoE). The drug works by controlling allergic inflammation of the esophagus. The esophagus is a food pipe that transfers food from the mouth into the stomach. Participants with EoE have dysfunction of the muscle of the esophagus (impaired peristalsis) that is not favorable for the transport function. Main question this study aims to answer is: Whether Dupilumab helps improve muscle activity of the esophagus in participants with EOE? Participants will: Take Dupilumab every week for 12 weeks. Visit the clinic before and after starting the medication. Keep a diary of symptoms.

Timeline

Start

2024-11-10

Primary completion

2026-09-15

Completion

2026-11-14

Publications

• Background Ledgerwood-Lee M, Zifan A, Kunkel DC, Sah R, Mittal RK. High-frequency ultrasound imaging of the anal sphincter muscles in normal subjects and patients with fecal incontinence. Neurogastroenterol Motil. 2019 Apr;31(4):e13537. doi: 10.1111/nmo.13537. Epub 2019 Jan 24.
• Background Ledgerwood M, Zifan A, Lin W, de Alva J, Chen H, Mittal RK. Novel gel bolus to improve impedance-based measurements of esophageal cross-sectional area during primary peristalsis. Neurogastroenterol Motil. 2021 Jul;33(7):e14071. doi: 10.1111/nmo.14071. Epub 2020 Dec 29.
• Background Mittal RK, Liu J, Puckett JL, Bhalla V, Bhargava V, Tipnis N, Kassab G. Sensory and motor function of the esophagus: lessons from ultrasound imaging. Gastroenterology. 2005 Feb;128(2):487-97. doi: 10.1053/j.gastro.2004.08.004.
• Background Taft TH, Riehl M, Sodikoff JB, Kahrilas PJ, Keefer L, Doerfler B, Pandolfino JE. Development and validation of the brief esophageal dysphagia questionnaire. Neurogastroenterol Motil. 2016 Dec;28(12):1854-1860. doi: 10.1111/nmo.12889. Epub 2016 Jul 5.
• Background Dellon ES, Irani AM, Hill MR, Hirano I. Development and field testing of a novel patient-reported outcome measure of dysphagia in patients with eosinophilic esophagitis. Aliment Pharmacol Ther. 2013 Sep;38(6):634-42. doi: 10.1111/apt.12413. Epub 2013 Jul 9.
• Background Bhalla V, Liu J, Puckett JL, Mittal RK. Symptom hypersensitivity to acid infusion is associated with hypersensitivity of esophageal contractility. Am J Physiol Gastrointest Liver Physiol. 2004 Jul;287(1):G65-71. doi: 10.1152/ajpgi.00420.2003. Epub 2004 Feb 19.
• Background White RJ, Zhang Y, Morris GP, Paterson WG. Esophagitis-related esophageal shortening in opossum is associated with longitudinal muscle hyperresponsiveness. Am J Physiol Gastrointest Liver Physiol. 2001 Mar;280(3):G463-9. doi: 10.1152/ajpgi.2001.280.3.G463.
• Background Goyal RK, Chaudhury A. Physiology of normal esophageal motility. J Clin Gastroenterol. 2008 May-Jun;42(5):610-9. doi: 10.1097/MCG.0b013e31816b444d.
• Background Zifan A, Song HJ, Youn YH, Qiu X, Ledgerwood-Lee M, Mittal RK. Topographical plots of esophageal distension and contraction: effects of posture on esophageal peristalsis and bolus transport. Am J Physiol Gastrointest Liver Physiol. 2019 Apr 1;316(4):G519-G526. doi: 10.1152/ajpgi.00397.2018. Epub 2019 Jan 24.
• Background Mittal RK, Muta K, Ledgerwood-Lee M, Gandu V, Zifan A. Abnormal Esophageal Distension Profiles in Patients With Functional Dysphagia: A Possible Mechanism of Dysphagia. Gastroenterology. 2021 Apr;160(5):1847-1849.e2. doi: 10.1053/j.gastro.2020.12.002. Epub 2020 Dec 8. No abstract available.
• Background Muta K, Mittal RK, Zifan A. Rhythmic contraction but arrhythmic distension of esophageal peristaltic reflex in patients with dysphagia. PLoS One. 2022 Jan 24;17(1):e0262948. doi: 10.1371/journal.pone.0262948. eCollection 2022.
• Background Zifan A, Muta K, Mittal RK. Distension-contraction profile of peristalsis in patients with nutcracker esophagus. Neurogastroenterol Motil. 2021 Nov;33(11):e14138. doi: 10.1111/nmo.14138. Epub 2021 Apr 5.
• Background Omari TI, Zifan A, Cock C, Mittal RK. Distension contraction plots of pharyngeal/esophageal peristalsis: next frontier in the assessment of esophageal motor function. Am J Physiol Gastrointest Liver Physiol. 2022 Sep 1;323(3):G145-G156. doi: 10.1152/ajpgi.00124.2022. Epub 2022 Jul 5.
• Background Zifan A, Ledgerwood-Lee M, Mittal RK. Measurement of peak esophageal luminal cross-sectional area utilizing nadir intraluminal impedance. Neurogastroenterol Motil. 2015 Jul;27(7):971-80. doi: 10.1111/nmo.12571. Epub 2015 Apr 30.
• Background Nicodeme F, Hirano I, Chen J, Robinson K, Lin Z, Xiao Y, Gonsalves N, Kwasny MJ, Kahrilas PJ, Pandolfino JE. Esophageal distensibility as a measure of disease severity in patients with eosinophilic esophagitis. Clin Gastroenterol Hepatol. 2013 Sep;11(9):1101-1107.e1. doi: 10.1016/j.cgh.2013.03.020. Epub 2013 Apr 13.
• Background Mittal RK. Regulation and dysregulation of esophageal peristalsis by the integrated function of circular and longitudinal muscle layers in health and disease. Am J Physiol Gastrointest Liver Physiol. 2016 Sep 1;311(3):G431-43. doi: 10.1152/ajpgi.00182.2016. Epub 2016 Jul 21.
• Background Korsapati H, Babaei A, Bhargava V, Dohil R, Quin A, Mittal RK. Dysfunction of the longitudinal muscles of the oesophagus in eosinophilic oesophagitis. Gut. 2009 Aug;58(8):1056-62. doi: 10.1136/gut.2008.168146. Epub 2009 Jan 9.
• Background Lucendo AJ, Castillo P, Martin-Chavarri S, Carrion G, Pajares R, Pascual JM, Mancenido N, Erdozain JC. Manometric findings in adult eosinophilic oesophagitis: a study of 12 cases. Eur J Gastroenterol Hepatol. 2007 May;19(5):417-24. doi: 10.1097/MEG.0b013e328010bd69.
• Background Nurko S, Rosen R. Esophageal dysmotility in patients who have eosinophilic esophagitis. Gastrointest Endosc Clin N Am. 2008 Jan;18(1):73-89; ix. doi: 10.1016/j.giec.2007.09.006.
• Background Dellon ES, Rothenberg ME, Collins MH, Hirano I, Chehade M, Bredenoord AJ, Lucendo AJ, Spergel JM, Aceves S, Sun X, Kosloski MP, Kamal MA, Hamilton JD, Beazley B, McCann E, Patel K, Mannent LP, Laws E, Akinlade B, Amin N, Lim WK, Wipperman MF, Ruddy M, Patel N, Weinreich DR, Yancopoulos GD, Shumel B, Maloney J, Giannelou A, Shabbir A. Dupilumab in Adults and Adolescents with Eosinophilic Esophagitis. N Engl J Med. 2022 Dec 22;387(25):2317-2330. doi: 10.1056/NEJMoa2205982.
• 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 Rajan J, Newbury RO, Anilkumar A, Dohil R, Broide DH, Aceves SS. Long-term assessment of esophageal remodeling in patients with pediatric eosinophilic esophagitis treated with topical corticosteroids. J Allergy Clin Immunol. 2016 Jan;137(1):147-156.e8. doi: 10.1016/j.jaci.2015.05.045. Epub 2015 Jul 30.
• 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 Blanchard C, Stucke EM, Burwinkel K, Caldwell JM, Collins MH, Ahrens A, Buckmeier BK, Jameson SC, Greenberg A, Kaul A, Franciosi JP, Kushner JP, Martin LJ, Putnam PE, Abonia JP, Wells SI, Rothenberg ME. Coordinate interaction between IL-13 and epithelial differentiation cluster genes in eosinophilic esophagitis. J Immunol. 2010 Apr 1;184(7):4033-41. doi: 10.4049/jimmunol.0903069. Epub 2010 Mar 5.
• Background Hirano I, Dellon ES, Hamilton JD, Collins MH, Peterson K, Chehade M, Schoepfer AM, Safroneeva E, Rothenberg ME, Falk GW, Assouline-Dayan Y, Zhao Q, Chen Z, Swanson BN, Pirozzi G, Mannent L, Graham NMH, Akinlade B, Stahl N, Yancopoulos GD, Radin A. Efficacy of Dupilumab in a Phase 2 Randomized Trial of Adults With Active Eosinophilic Esophagitis. Gastroenterology. 2020 Jan;158(1):111-122.e10. doi: 10.1053/j.gastro.2019.09.042. Epub 2019 Oct 5.
• Background Hirano I, Aceves SS. Clinical implications and pathogenesis of esophageal remodeling in eosinophilic esophagitis. Gastroenterol Clin North Am. 2014 Jun;43(2):297-316. doi: 10.1016/j.gtc.2014.02.015. Epub 2014 Apr 16.
• Background Abonia JP, Rothenberg ME. Eosinophilic esophagitis: rapidly advancing insights. Annu Rev Med. 2012;63:421-34. doi: 10.1146/annurev-med-041610-134138. Epub 2011 Oct 27.
• Background Falk GW. Clinical presentation of eosinophilic esophagitis in adults. Gastroenterol Clin North Am. 2014 Jun;43(2):231-42. doi: 10.1016/j.gtc.2014.02.009. Epub 2014 Apr 1.
• Background Furuta GT, Aceves SS. The National Biome Initiative: An allergy perspective. J Allergy Clin Immunol. 2017 Apr;139(4):1131-1134. doi: 10.1016/j.jaci.2017.02.008. Epub 2017 Feb 28. No abstract available.
• Background Dellon ES, Hirano I. Epidemiology and Natural History of Eosinophilic Esophagitis. Gastroenterology. 2018 Jan;154(2):319-332.e3. doi: 10.1053/j.gastro.2017.06.067. Epub 2017 Aug 1.

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Indications