Clinical trial NCT03107819: Metabolomics for Biomarker Discovery in Children With EoE
Official title: Plasma and Urine Metabolomics for Biomarker Discovery in Children With Eosinophilic Esophagitis
Study type: OBSERVATIONAL
Overall status: COMPLETED
Conditions: Eosinophilic Esophagitis
Keywords: Plasma metabolomics
Urinary metabolomics
Metabonomics
Biomarker discovery
Lead sponsor: The University of Texas Health Science Center, Houston
Sponsor class: OTHER
Collaborators: name: Baylor College of Medicine
First posted: 2017-04-11
Enrollment: 24
Sex: ALL
Minimum age (years): 2
Maximum age (years): 18
Standard ages: CHILD
ADULT
Accepts healthy volunteers: no
Observational model: COHORT
Time perspective: PROSPECTIVE
Sampling method: PROBABILITY_SAMPLE
Study population: Children ages 2-18 years already undergoing upper endoscopy (EGD)

Brief summary: The investigators are seeking to enroll 8 children ages 2-18 already undergoing upper endoscopy. For the purposes of research, a peripheral blood and clean catch urine specimen will be obtained to measure plasma and urine metabolomics. The data will be used to determine if there are any key differences in the metabolite profile of subjects found to have eosinophilic esophagitis (EoE) versus non-EoE subjects. Once these metabolites are identified, the investigators will seek to enroll many more subjects for a validation phase.

Detailed description: Eosinophilic esophagitis (EoE) is a disorder of the esophagus triggered by food and/or environmental allergens and is characterized by symptoms of esophageal dysfunction and eosinophilia of the esophagus. The standard of care for diagnosing and monitoring EoE is with biopsies of the esophagus. There are currently no known biomarkers that correlate with the inflammatory activity of esophageal mucosa, and patients' symptoms alone are insufficient in providing a reliable assessment. Some studies report that patients with EoE may undergo endoscopy up to 11 times in one year. Finding a non-invasive biomarker would therefore be of high clinical and economic interest.

The investigators will seek to enroll 8 children ages 2-18 years already undergoing esophagogastroduodenoscopy (EGD). For the purposes of research, a peripheral blood specimen will be collected at the same time of peripheral intravenous (IV) placement, which is routinely performed for the purposes of sedation during endoscopy, thereby avoiding extra needle sticks. A urine sample will also be collected on the day of the EGD. These specimens will then be analyzed for plasma and urine metabolomics to evaluate for any derangements in EoE versus non-EoE subjects.

Risks to participants undergoing EGD are the same as they would be if they were not enrolled in the study as no additional biopsies will be taken. Risks associated with a blood draw are minimal and include some discomfort, such as lightheadedness, fainting, bruising, soreness, clotting and bleeding at the site of the needle stick, and in rare cases, infection. Collection of the urine specimen is by clean catch in only toilet-trained individuals.

This study should yield valuable information regarding plasma and urine metabolomics in EoE versus non-EoE subjects. Once this "discovery" data set is analyzed, future research could then focus specifically on those abnormal metabolites and seek to enroll many more subjects for a validation phase.

Eligibility criteria: Inclusion Criteria:

1. Pediatric patients, ages 2-18 years, undergoing EGD with biopsies of the esophagus.
2. Children with known EoE will only be enrolled if his/her biopsy on the day of specimen collection demonstrates ≥15 eosinophils (eos) per high power field (hpf).

Exclusion Criteria:

1. Presence of other disorders associated with similar clinical, histological or endoscopic features, such as proton pump inhibitor (PPI)-responsive esophageal eosinophilia, esophageal eosinophilia associated with gastroesophageal reflux, Crohn's disease, infectious esophagitis (i.e. herpes simplex virus or candida), drug-associated esophagitis, collagen vascular disease, hypereosinophilic syndrome and eosinophilic gastroenteritis.
2. Children with known EoE and biopsy demonstrating \<15 eos/hpf at the time of specimen collection.
3. Inability to provide a clean catch urine specimen (i.e. not toilet-trained).

Primary outcomes:
measure: Plasma and urine metabolomics
timeFrame: baseline
Secondary outcomes:
Other outcomes:
Locations:
city: Houston
country: United States
facility: University of Texas Health Science Center
state: Texas
Study officials:
affiliation: The University of Texas Health Science Center, Houston
name: Jon M Rhoads, MD
role: STUDY_DIRECTOR
References:
citation: 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.
citation: Gupta SK. Noninvasive markers of eosinophilic esophagitis. Gastrointest Endosc Clin N Am. 2008 Jan;18(1):157-67; xi. doi: 10.1016/j.giec.2007.09.004.
citation: 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.
citation: Cianferoni A, Spergel JM. Immunotherapeutic approaches for the treatment of eosinophilic esophagitis. Immunotherapy. 2014;6(3):321-31. doi: 10.2217/imt.14.3.
citation: Schlag C, Miehlke S, Heiseke A, Brockow K, Krug A, von Arnim U, Straumann A, Vieth M, Bussmann C, Mueller R, Greinwald R, Bajbouj M. Peripheral blood eosinophils and other non-invasive biomarkers can monitor treatment response in eosinophilic oesophagitis. Aliment Pharmacol Ther. 2015 Nov;42(9):1122-30. doi: 10.1111/apt.13386. Epub 2015 Aug 27.
citation: Kagalwalla AF, Shah A, Li BU, Sentongo TA, Ritz S, Manuel-Rubio M, Jacques K, Wang D, Melin-Aldana H, Nelson SP. Identification of specific foods responsible for inflammation in children with eosinophilic esophagitis successfully treated with empiric elimination diet. J Pediatr Gastroenterol Nutr. 2011 Aug;53(2):145-9. doi: 10.1097/MPG.0b013e31821cf503.
citation: Molina-Infante J, Arias A, Barrio J, Rodriguez-Sanchez J, Sanchez-Cazalilla M, Lucendo AJ. Four-food group elimination diet for adult eosinophilic esophagitis: A prospective multicenter study. J Allergy Clin Immunol. 2014 Nov;134(5):1093-9.e1. doi: 10.1016/j.jaci.2014.07.023. Epub 2014 Aug 28.
citation: Patti GJ, Yanes O, Siuzdak G. Innovation: Metabolomics: the apogee of the omics trilogy. Nat Rev Mol Cell Biol. 2012 Mar 22;13(4):263-9. doi: 10.1038/nrm3314.
citation: Collino S, Martin FP, Rezzi S. Clinical metabolomics paves the way towards future healthcare strategies. Br J Clin Pharmacol. 2013 Mar;75(3):619-29. doi: 10.1111/j.1365-2125.2012.04216.x.
citation: Zhang A, Sun H, Wang P, Han Y, Wang X. Modern analytical techniques in metabolomics analysis. Analyst. 2012 Jan 21;137(2):293-300. doi: 10.1039/c1an15605e. Epub 2011 Nov 21.
citation: Sarosiek I, Schicho R, Blandon P, Bashashati M. Urinary metabolites as noninvasive biomarkers of gastrointestinal diseases: A clinical review. World J Gastrointest Oncol. 2016 May 15;8(5):459-65. doi: 10.4251/wjgo.v8.i5.459.
citation: Stephens NS, Siffledeen J, Su X, Murdoch TB, Fedorak RN, Slupsky CM. Urinary NMR metabolomic profiles discriminate inflammatory bowel disease from healthy. J Crohns Colitis. 2013 Mar;7(2):e42-8. doi: 10.1016/j.crohns.2012.04.019. Epub 2012 May 22.
citation: Davis VW, Schiller DE, Eurich D, Sawyer MB. Urinary metabolomic signature of esophageal cancer and Barrett's esophagus. World J Surg Oncol. 2012 Dec 15;10:271. doi: 10.1186/1477-7819-10-271.
citation: Jung J, Jung Y, Bang EJ, Cho SI, Jang YJ, Kwak JM, Ryu DH, Park S, Hwang GS. Noninvasive diagnosis and evaluation of curative surgery for gastric cancer by using NMR-based metabolomic profiling. Ann Surg Oncol. 2014 Dec;21 Suppl 4:S736-42. doi: 10.1245/s10434-014-3886-0. Epub 2014 Aug 5.
citation: Qiu Y, Cai G, Su M, Chen T, Liu Y, Xu Y, Ni Y, Zhao A, Cai S, Xu LX, Jia W. Urinary metabonomic study on colorectal cancer. J Proteome Res. 2010 Mar 5;9(3):1627-34. doi: 10.1021/pr901081y.
citation: Bertini I, Calabro A, De Carli V, Luchinat C, Nepi S, Porfirio B, Renzi D, Saccenti E, Tenori L. The metabonomic signature of celiac disease. J Proteome Res. 2009 Jan;8(1):170-7. doi: 10.1021/pr800548z.