Clinical trial NCT00909350: Micro-RNA (miR) Expression in Upper Gastrointestinal Mucosal Tissue
Official title: Micro-RNA (miR) Expression in Upper Gastrointestinal Mucosal Tissue: A Potential Target for Understanding and Preventing the Progression of Barrett's Esophagus
Study type: OBSERVATIONAL
Overall status: COMPLETED
Conditions: Barrett's Esophagus
Esophageal Adenocarcinoma
Keywords: Barrett's esophagus
BE
esophageal adenocarcinoma
Micro-RNA
miR expression
Lead sponsor: Mayo Clinic
Sponsor class: OTHER
First posted: 2009-05-28
Enrollment: 10
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: yes
Observational model: CASE_ONLY
Time perspective: PROSPECTIVE
Sampling method: NON_PROBABILITY_SAMPLE
Study population: Study subjects identified from individuals referred for upper endoscopy at Mayo Clinic in Jacksonville, Florida

Brief summary: This is a laboratory-based, exploratory study using tissue obtained from our clinical practice. The purpose of this study is to confirm our ability to characterize miR expression in various tissues (proximal and distal esophagus, stomach and duodenum) obtained from the upper gastrointestinal tract in preparation for the study of MiR in patients with Barrett's esophagus and other inflammatory conditions of the upper gastrointestinal tract.

Detailed description: The incidence of esophageal adenocarcinoma has increased dramatically over the past three decades. These adenocarcinomas usually arise from columnar lined epithelium of the esophagus known as Barrett's esophagus (BE). There is an established association between gastroesophageal reflux disease (GERD) and the development of BE and esophageal adenocarcinoma. In an attempt to diagnose esophageal adenocarcinoma at an earlier and more treatable stage, efforts have been directed at identifying patients with BE and enrolling them in surveillance protocols. Several authors have challenged this strategy since it has not yet been proven to save lives and is very expensive. A major unresolved problem is the fact that the clinical factors considered to be somewhat predictive of the presence or absence of BE are neither sufficiently sensitive nor specific. In addition, once BE is identified, predicting who may or may not progress to cancer is far from perfect. A molecular understanding of why certain patients develop BE and why certain of those progress to cancer is of obvious importance.

The molecular pathway from normal esophageal mucosa to Barrett's esophagus and on to adenocarcinoma is not well understood. Micro-RNA (miR) RNAs have recently emerged as important regulators of carcinogenesis and have not been studied in BE. We seek to confirm our ability to characterize miR expression in various tissues (esophagus, stomach and duodenum) obtained from the upper gastrointestinal tract in preparation for the study of MiR in patients with Barrett's esophagus and other inflammatory conditions of the upper gastrointestinal tract.

This study will involve collection of tissue via endoscopic biopsy in 10 patients with normal endoscopic appearance from the esophagus, stomach and duodenum. Ambion miR oligonucleotide arrays will be utilized to profile miRs that are specifically expressed in epithelial biopsies from the duodenum, stomach, and esophagus. Total RNA will be extracted from independent biopsy samples using the mirVana(R) micro RNA isolation kit from Ambion. The Ambion Flash PAGE(R) electrophoresis system will be used to resolve mature miRs from the larger pre-miR species. Mature miRs will be labeled and hybridized to Ambion mirVana miR(R)arrays, which will be scanned to identify miRs that are regulated under these circumstances. Signals from the microarrays will be processed using the R functions of Bioconductor for normalization and background correction and RMA for summarization. Statistical significance will be determined using Insightful S+ functions and assuming a least pooled error model. Potential targets will be confirmed by northern blotting. The routine histology sample will be reviewed simply to exclude other, unexpected microscopic pathology. Benign histologic findings such as minor inflammation, will not exclude the patient from inclusion. If there is a wide variation in miR expression, then the histology might be needed to help explain such variation.

Eligibility criteria: Inclusion Criteria:

* willingness to give consent
* normal gross appearance of the esophagus, stomach and duodenum

Exclusion Criteria:

* contraindication to mucosal biopsy

Primary outcomes:
measure: miR expression between tissue from Barrett's esophagus and that from normal tissues
timeFrame: time it takes to have standard of care biopsies taken during one routine Upper Endoscopy
Secondary outcomes:
measure: expression of miR in Barrett's esophagus patients with cancer in comparison to those who do not progress to cancer
timeFrame: time it takes to have standard of care biopsies during one routine Upper Endoscopy
Other outcomes:
Locations:
city: Jacksonville
country: United States
facility: Mayo Clinic
state: Florida
Study officials:
affiliation: Mayo Clinic, Jacksonville, Florida
name: Kenneth R. DeVault,, M.D.
role: PRINCIPAL_INVESTIGATOR
References: