Evaluation of MicroRNA Expression in Blood and Cytology for Detecting Barrett's Esophagus and Associated Neoplasia

NCT02464930 | Unknown

• 1 other identifier: AB0009
• Study Type: observational
• Target: 220
• Locations: 1 country
• Sites: 1

Brief Summary

The primary purpose of this study is to test new methods to diagnose BE in time before it turns into advanced cancer. Once BE is diagnosed, the current standard of care is to monitor the disease so that complication such as cancer can be diagnosed early. The two new methods the investigators are evaluating are: a) blood test and b) brush test of the food pipe. The investigators will collect blood, bile and cells from the food pipe and stomach and measure for a biomarker called microRNA (miRNA). In the future, measurements of microRNA biomarkers could help the doctors figure out which patients are at increased risk for cancer of the esophagus.

Conditions

Barrett's Esophagus; Gastroesophageal Reflux; Esophageal Adenocarcinoma

Keywords

Blood; Cytology; Esophagus; microRNA

Outcome Measures

Primary Outcomes (1)

• Sensitivity and specificity of tissue and serum microRNA expression by digital polymerase chain reaction for diagnosis of BE neoplasia

  The two main outcomes are the diagnostic accuracy of tissue and serum microRNA for the the diagnosis of Barrett's esophagus compared to endoscopy.

  1-3 years

Secondary Outcomes (1)

• Differences in the microRNA expression of biliary exosomes between GERD, Barrett's esophagus and Cancer

  1-3 years

Study Arms (3)

No-GERD Controls

NERD controls will be enrolled from subjects presenting to the endoscopy unit who are being evaluated for reasons other than GERD or BE surveillance. These are patients who are referred to the endoscopy unit for: evaluation of anemia, dysphagia, occult blood positivity, gastrointestinal blood loss etc. * No history of GERD * Response "no" to presence of symptoms on a standardized GERD questionnaire * No prescriptions for acid suppressive medication over the past 2 years as documented in electronic pharmacy records. * Normal endoscopy that does not find Barrett's esophagus, hiatus hernia or erosive esophagitis.

GERD Controls

* Respond "yes" to the presence of symptoms on a standardized GERD questionnaire * Prescriptions for acid suppressive medication as documented in electronic pharmacy records.

BE Cases

• Patients who present for evaluation of reflux symptoms and are found to have at least 1 cm of columnar lined esophagus on endoscopy with intestinal metaplasia on biopsies. This will include patients with esophageal adenocarcinoma

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: Yes
• Age Groups: Adult (18-64), Older Adult (65+)
• Sampling Method: Non-Probability Sample

Study Population

Patients will be recruited at the Kansas City VA Hospital and the Mobile Medical unit of the Kansas City VA. The Mobile Medical Unit (MMU) travels to multiple counties to provide health care to the veterans at their doorstep. This is a program that has been in place for several years and continues to grow. Currently, the MMU provides services such as basic health evaluations and phlebotomy to \~600 veterans per week.

You may qualify if:

• Patient age: \> 18 years
• Ability to provide written, informed consent

You may not qualify if:

• Pregnancy or planning a pregnancy
• History of nasal, esophageal \& gastric surgery
• History of recurrent epistaxis or nasal trauma
• Subjects with a history of unresolved drug or alcohol dependency
• Inability to obtain biopsies due to a coagulopathy, varices, thrombocytopenia, etc.
• Subjects with inadequate cytology specimens will not undergo repeat test and will be excluded from the study
• Inability to provide written informed consent
• Inability to discontinue drugs such as Plavix
• Advanced chronic liver disease
• Severe uncontrolled coagulopathy
• Active cancer in any organ over the past 3 years.

Sponsors & Collaborators

• Midwest Biomedical Research Foundation: lead
• Kansas City Veteran Affairs Medical Center: collaborator
• University of Kansas: collaborator

Study Sites (1)

Kansas City Veterans Affairs Medical Center

Kansas City, Missouri, 64128, United States

RECRUITING

Related Publications (43)

• El-Serag HB, Sweet S, Winchester CC, Dent J. Update on the epidemiology of gastro-oesophageal reflux disease: a systematic review. Gut. 2014 Jun;63(6):871-80. doi: 10.1136/gutjnl-2012-304269. Epub 2013 Jul 13.

  PMID: 23853213 BACKGROUND

• Spechler SJ, Souza RF. Barrett's esophagus. N Engl J Med. 2014 Aug 28;371(9):836-45. doi: 10.1056/NEJMra1314704. No abstract available.

  PMID: 25162890 BACKGROUND

• Rajendra S, Sharma P. Barrett's Esophagus. Curr Treat Options Gastroenterol. 2014 Jun;12(2):169-82. doi: 10.1007/s11938-014-0012-0.

  PMID: 24634008 BACKGROUND

• Weaver JMJ, Ross-Innes CS, Shannon N, Lynch AG, Forshew T, Barbera M, Murtaza M, Ong CJ, Lao-Sirieix P, Dunning MJ, Smith L, Smith ML, Anderson CL, Carvalho B, O'Donovan M, Underwood TJ, May AP, Grehan N, Hardwick R, Davies J, Oloumi A, Aparicio S, Caldas C, Eldridge MD, Edwards PAW, Rosenfeld N, Tavare S, Fitzgerald RC; OCCAMS consortium. Ordering of mutations in preinvasive disease stages of esophageal carcinogenesis. Nat Genet. 2014 Aug;46(8):837-843. doi: 10.1038/ng.3013. Epub 2014 Jun 22.

  PMID: 24952744 BACKGROUND

• Hamilton SR, Smith RR, Cameron JL. Prevalence and characteristics of Barrett esophagus in patients with adenocarcinoma of the esophagus or esophagogastric junction. Hum Pathol. 1988 Aug;19(8):942-8. doi: 10.1016/s0046-8177(88)80010-8.

  PMID: 3402983 BACKGROUND

• di Pietro M, Alzoubaidi D, Fitzgerald RC. Barrett's esophagus and cancer risk: how research advances can impact clinical practice. Gut Liver. 2014 Jul;8(4):356-70. doi: 10.5009/gnl.2014.8.4.356. Epub 2014 Jul 1.

  PMID: 25071900 BACKGROUND

• American Gastroenterological Association; Spechler SJ, Sharma P, Souza RF, Inadomi JM, Shaheen NJ. American Gastroenterological Association medical position statement on the management of Barrett's esophagus. Gastroenterology. 2011 Mar;140(3):1084-91. doi: 10.1053/j.gastro.2011.01.030. No abstract available.

  PMID: 21376940 BACKGROUND

• Sharma P. Clinical practice. Barrett's esophagus. N Engl J Med. 2009 Dec 24;361(26):2548-56. doi: 10.1056/NEJMcp0902173. No abstract available.

  PMID: 20032324 BACKGROUND

• Hur C, Miller M, Kong CY, Dowling EC, Nattinger KJ, Dunn M, Feuer EJ. Trends in esophageal adenocarcinoma incidence and mortality. Cancer. 2013 Mar 15;119(6):1149-58. doi: 10.1002/cncr.27834. Epub 2012 Dec 11.

  PMID: 23303625 BACKGROUND

• Yousef F, Cardwell C, Cantwell MM, Galway K, Johnston BT, Murray L. The incidence of esophageal cancer and high-grade dysplasia in Barrett's esophagus: a systematic review and meta-analysis. Am J Epidemiol. 2008 Aug 1;168(3):237-49. doi: 10.1093/aje/kwn121. Epub 2008 Jun 12.

  PMID: 18550563 BACKGROUND

• Hvid-Jensen F, Pedersen L, Drewes AM, Sorensen HT, Funch-Jensen P. Incidence of adenocarcinoma among patients with Barrett's esophagus. N Engl J Med. 2011 Oct 13;365(15):1375-83. doi: 10.1056/NEJMoa1103042.

  PMID: 21995385 BACKGROUND

• Reid BJ, Li X, Galipeau PC, Vaughan TL. Barrett's oesophagus and oesophageal adenocarcinoma: time for a new synthesis. Nat Rev Cancer. 2010 Feb;10(2):87-101. doi: 10.1038/nrc2773.

  PMID: 20094044 BACKGROUND

• Montgomery E, Goldblum JR, Greenson JK, Haber MM, Lamps LW, Lauwers GY, Lazenby AJ, Lewin DN, Robert ME, Washington K, Zahurak ML, Hart J. Dysplasia as a predictive marker for invasive carcinoma in Barrett esophagus: a follow-up study based on 138 cases from a diagnostic variability study. Hum Pathol. 2001 Apr;32(4):379-88. doi: 10.1053/hupa.2001.23511.

  PMID: 11331954 BACKGROUND

• Shaheen NJ, Hur C. Garlic, silver bullets, and surveillance upper endoscopy for Barrett's esophagus. Gastroenterology. 2013 Aug;145(2):273-6. doi: 10.1053/j.gastro.2013.06.028. Epub 2013 Jun 24. No abstract available.

  PMID: 23806540 BACKGROUND

• Kadri SR, Lao-Sirieix P, O'Donovan M, Debiram I, Das M, Blazeby JM, Emery J, Boussioutas A, Morris H, Walter FM, Pharoah P, Hardwick RH, Fitzgerald RC. Acceptability and accuracy of a non-endoscopic screening test for Barrett's oesophagus in primary care: cohort study. BMJ. 2010 Sep 10;341:c4372. doi: 10.1136/bmj.c4372.

  PMID: 20833740 BACKGROUND

• Bansal A, Lee IH, Hong X, Anand V, Mathur SC, Gaddam S, Rastogi A, Wani SB, Gupta N, Visvanathan M, Sharma P, Christenson LK. Feasibility of mcroRNAs as biomarkers for Barrett's Esophagus progression: a pilot cross-sectional, phase 2 biomarker study. Am J Gastroenterol. 2011 Jun;106(6):1055-63. doi: 10.1038/ajg.2011.37. Epub 2011 Mar 15.

  PMID: 21407181 BACKGROUND

• Bhardwaj A, Hollenbeak CS, Pooran N, Mathew A. A meta-analysis of the diagnostic accuracy of esophageal capsule endoscopy for Barrett's esophagus in patients with gastroesophageal reflux disease. Am J Gastroenterol. 2009 Jun;104(6):1533-9. doi: 10.1038/ajg.2009.86. Epub 2009 Apr 21.

  PMID: 19491867 BACKGROUND

• Gora MJ, Sauk JS, Carruth RW, Lu W, Carlton DT, Soomro A, Rosenberg M, Nishioka NS, Tearney GJ. Imaging the upper gastrointestinal tract in unsedated patients using tethered capsule endomicroscopy. Gastroenterology. 2013 Oct;145(4):723-5. doi: 10.1053/j.gastro.2013.07.053. Epub 2013 Aug 8. No abstract available.

  PMID: 23932950 BACKGROUND

• Benaglia T, Sharples LD, Fitzgerald RC, Lyratzopoulos G. Health benefits and cost effectiveness of endoscopic and nonendoscopic cytosponge screening for Barrett's esophagus. Gastroenterology. 2013 Jan;144(1):62-73.e6. doi: 10.1053/j.gastro.2012.09.060. Epub 2012 Oct 3.

  PMID: 23041329 BACKGROUND

• Rajewsky N. microRNA target predictions in animals. Nat Genet. 2006 Jun;38 Suppl:S8-13. doi: 10.1038/ng1798.

  PMID: 16736023 BACKGROUND

• Cortez MA, Bueso-Ramos C, Ferdin J, Lopez-Berestein G, Sood AK, Calin GA. MicroRNAs in body fluids--the mix of hormones and biomarkers. Nat Rev Clin Oncol. 2011 Jun 7;8(8):467-77. doi: 10.1038/nrclinonc.2011.76.

  PMID: 21647195 BACKGROUND

• Liu N, Chen NY, Cui RX, Li WF, Li Y, Wei RR, Zhang MY, Sun Y, Huang BJ, Chen M, He QM, Jiang N, Chen L, Cho WC, Yun JP, Zeng J, Liu LZ, Li L, Guo Y, Wang HY, Ma J. Prognostic value of a microRNA signature in nasopharyngeal carcinoma: a microRNA expression analysis. Lancet Oncol. 2012 Jun;13(6):633-41. doi: 10.1016/S1470-2045(12)70102-X. Epub 2012 May 3.

  PMID: 22560814 BACKGROUND

• Lu J, Getz G, Miska EA, Alvarez-Saavedra E, Lamb J, Peck D, Sweet-Cordero A, Ebert BL, Mak RH, Ferrando AA, Downing JR, Jacks T, Horvitz HR, Golub TR. MicroRNA expression profiles classify human cancers. Nature. 2005 Jun 9;435(7043):834-8. doi: 10.1038/nature03702.

  PMID: 15944708 BACKGROUND

• Wang S, Wang L, Bayaxi N, Li J, Verhaegh W, Janevski A, Varadan V, Ren Y, Merkle D, Meng X, Gao X, Wang H, Ren J, Kuo WP, Dimitrova N, Wu Y, Zhu H. A microRNA panel to discriminate carcinomas from high-grade intraepithelial neoplasms in colonoscopy biopsy tissue. Gut. 2013 Feb;62(2):280-9. doi: 10.1136/gutjnl-2011-301554. Epub 2012 Apr 25.

  PMID: 22535378 BACKGROUND

• Lujambio A, Lowe SW. The microcosmos of cancer. Nature. 2012 Feb 15;482(7385):347-55. doi: 10.1038/nature10888.

  PMID: 22337054 BACKGROUND

• Raposo G, Stoorvogel W. Extracellular vesicles: exosomes, microvesicles, and friends. J Cell Biol. 2013 Feb 18;200(4):373-83. doi: 10.1083/jcb.201211138.

  PMID: 23420871 BACKGROUND

• Zaidi AH, Gopalakrishnan V, Kasi PM, Zeng X, Malhotra U, Balasubramanian J, Visweswaran S, Sun M, Flint MS, Davison JM, Hood BL, Conrads TP, Bergman JJ, Bigbee WL, Jobe BA. Evaluation of a 4-protein serum biomarker panel-biglycan, annexin-A6, myeloperoxidase, and protein S100-A9 (B-AMP)-for the detection of esophageal adenocarcinoma. Cancer. 2014 Dec 15;120(24):3902-13. doi: 10.1002/cncr.28963. Epub 2014 Aug 5.

  PMID: 25100294 BACKGROUND

• Varghese S, Lao-Sirieix P, Fitzgerald RC. Identification and clinical implementation of biomarkers for Barrett's esophagus. Gastroenterology. 2012 Mar;142(3):435-441.e2. doi: 10.1053/j.gastro.2012.01.013. Epub 2012 Jan 20. No abstract available.

  PMID: 22266150 BACKGROUND

• Garman KS, Owzar K, Hauser ER, Westfall K, Anderson BR, Souza RF, Diehl AM, Provenzale D, Shaheen NJ. MicroRNA expression differentiates squamous epithelium from Barrett's esophagus and esophageal cancer. Dig Dis Sci. 2013 Nov;58(11):3178-88. doi: 10.1007/s10620-013-2806-7. Epub 2013 Aug 8.

  PMID: 23925817 BACKGROUND

• Sakai NS, Samia-Aly E, Barbera M, Fitzgerald RC. A review of the current understanding and clinical utility of miRNAs in esophageal cancer. Semin Cancer Biol. 2013 Dec;23(6 Pt B):512-21. doi: 10.1016/j.semcancer.2013.08.005. Epub 2013 Sep 3.

  PMID: 24013023 BACKGROUND

• Talsma AK, Ong CA, Liu X, van Hagen P, Van Lanschot JJ, Tilanus HW, Hardwick RH, Carroll NR, Spaander MC, Fitzgerald RC, Wijnhoven BP. Location of lymph node involvement in patients with esophageal adenocarcinoma predicts survival. World J Surg. 2014 Jan;38(1):106-13. doi: 10.1007/s00268-013-2236-x.

  PMID: 24101018 BACKGROUND

• Wang K, Zhang S, Marzolf B, Troisch P, Brightman A, Hu Z, Hood LE, Galas DJ. Circulating microRNAs, potential biomarkers for drug-induced liver injury. Proc Natl Acad Sci U S A. 2009 Mar 17;106(11):4402-7. doi: 10.1073/pnas.0813371106. Epub 2009 Feb 25.

  PMID: 19246379 BACKGROUND

• Wang WS, Liu LX, Li GP, Chen Y, Li CY, Jin DY, Wang XL. Combined serum CA19-9 and miR-27a-3p in peripheral blood mononuclear cells to diagnose pancreatic cancer. Cancer Prev Res (Phila). 2013 Apr;6(4):331-8. doi: 10.1158/1940-6207.CAPR-12-0307. Epub 2013 Feb 19.

  PMID: 23430754 BACKGROUND

• Weiland M, Gao XH, Zhou L, Mi QS. Small RNAs have a large impact: circulating microRNAs as biomarkers for human diseases. RNA Biol. 2012 Jun;9(6):850-9. doi: 10.4161/rna.20378. Epub 2012 Jun 1.

  PMID: 22699556 BACKGROUND

• Arroyo JD, Chevillet JR, Kroh EM, Ruf IK, Pritchard CC, Gibson DF, Mitchell PS, Bennett CF, Pogosova-Agadjanyan EL, Stirewalt DL, Tait JF, Tewari M. Argonaute2 complexes carry a population of circulating microRNAs independent of vesicles in human plasma. Proc Natl Acad Sci U S A. 2011 Mar 22;108(12):5003-8. doi: 10.1073/pnas.1019055108. Epub 2011 Mar 7.

  PMID: 21383194 BACKGROUND

• Beg MS, Navaneethan U, Atiq M, Komrokji R, Safa M. Outcome of esophageal carcinoma in the veteran affairs population: a comparative analysis from the Veteran Affairs Central Cancer Registry. Am J Clin Oncol. 2009 Jun;32(3):286-90. doi: 10.1097/COC.0b013e31818af0d8.

  PMID: 19433959 BACKGROUND

• Lao-Sirieix P, Boussioutas A, Kadri SR, O'Donovan M, Debiram I, Das M, Harihar L, Fitzgerald RC. Non-endoscopic screening biomarkers for Barrett's oesophagus: from microarray analysis to the clinic. Gut. 2009 Nov;58(11):1451-9. doi: 10.1136/gut.2009.180281. Epub 2009 Aug 2.

  PMID: 19651633 BACKGROUND

• Wang KK, Sampliner RE; Practice Parameters Committee of the American College of Gastroenterology. Updated guidelines 2008 for the diagnosis, surveillance and therapy of Barrett's esophagus. Am J Gastroenterol. 2008 Mar;103(3):788-97. doi: 10.1111/j.1572-0241.2008.01835.x. No abstract available.

  PMID: 18341497 BACKGROUND

• Sharma P, Dent J, Armstrong D, Bergman JJ, Gossner L, Hoshihara Y, Jankowski JA, Junghard O, Lundell L, Tytgat GN, Vieth M. The development and validation of an endoscopic grading system for Barrett's esophagus: the Prague C & M criteria. Gastroenterology. 2006 Nov;131(5):1392-9. doi: 10.1053/j.gastro.2006.08.032. Epub 2006 Aug 16.

  PMID: 17101315 BACKGROUND

• Tuck MK, Chan DW, Chia D, Godwin AK, Grizzle WE, Krueger KE, Rom W, Sanda M, Sorbara L, Stass S, Wang W, Brenner DE. Standard operating procedures for serum and plasma collection: early detection research network consensus statement standard operating procedure integration working group. J Proteome Res. 2009 Jan;8(1):113-7. doi: 10.1021/pr800545q.

  PMID: 19072545 BACKGROUND

• Montgomery E, Bronner MP, Goldblum JR, Greenson JK, Haber MM, Hart J, Lamps LW, Lauwers GY, Lazenby AJ, Lewin DN, Robert ME, Toledano AY, Shyr Y, Washington K. Reproducibility of the diagnosis of dysplasia in Barrett esophagus: a reaffirmation. Hum Pathol. 2001 Apr;32(4):368-78. doi: 10.1053/hupa.2001.23510.

  PMID: 11331953 BACKGROUND

• Bansal A, Lee IH, Hong X, Mathur SC, Tawfik O, Rastogi A, Buttar N, Visvanathan M, Sharma P, Christenson LK. Discovery and validation of Barrett's esophagus microRNA transcriptome by next generation sequencing. PLoS One. 2013;8(1):e54240. doi: 10.1371/journal.pone.0054240. Epub 2013 Jan 23.

  PMID: 23372692 BACKGROUND

• Schisterman EF, Perkins NJ, Liu A, Bondell H. Optimal cut-point and its corresponding Youden Index to discriminate individuals using pooled blood samples. Epidemiology. 2005 Jan;16(1):73-81. doi: 10.1097/01.ede.0000147512.81966.ba.

  PMID: 15613948 BACKGROUND

Biospecimen

Retention: SAMPLES WITH DNA

blood, bile and tissue in a repository

MeSH Terms

Conditions

Barrett Esophagus; Gastroesophageal Reflux; Adenocarcinoma Of Esophagus

Condition Hierarchy (Ancestors)

Precancerous Conditions; Neoplasms; Esophageal Diseases; Gastrointestinal Diseases; Digestive System Diseases; Esophageal Motility Disorders; Deglutition Disorders

Study Officials

• Ajay Bansal, MD

  Veterans Affairs Medical Center and the University of Kansas Medical Center

  PRINCIPAL INVESTIGATOR

Central Study Contacts

Ajay Bansal, MD

CONTACT

57790; ajay.bansal@va.gov

Andrew Price, BS

CONTACT

56428; andrew.price@va.gov

Study Design

• Study Type: observational
• Observational Model: CASE CONTROL
• Time Perspective: PROSPECTIVE
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Associate Professor of Medicine and Staff Gastroenterologist

Study Record Dates

• First Submitted: June 2, 2015
• First Posted: June 8, 2015
• Study Start: April 1, 2015
• Primary Completion: April 1, 2018
• Study Completion: December 1, 2018
• Last Updated: June 8, 2015

Record last verified: 2015-06

Locations

US (1)