Ignite Creation Date:
2024-05-06 @ 11:27 AM
Last Modification Date:
2024-10-26 @ 12:45 PM
Study NCT ID:
NCT03526328
Status:
COMPLETED
Last Update Posted:
2020-03-06
First Post:
2013-09-26
Brief Title:
DCLK1 as a MarkerIndicator of Stem Cell Response in Barretts EsophagusEsophageal Adenocarcinoma
Sponsor:
University of Oklahoma
Organization:
University of Oklahoma
Study Overview
Official Title:
Doublecortin Like Kinase-1 as a Marker and Indicator of Treatment Response for Intestinal Stem Cells in Barretts Esophagus and Progression to Esophageal Adenocarcinoma
Status:
COMPLETED
Status Verified Date:
2020-03
Last Known Status:
None
Delayed Posting:
No
If Stopped, Why?:
Not Stopped
Has Expanded Access:
False
If Expanded Access, NCT#:
N/A
Has Expanded Access, NCT# Status:
N/A
Acronym:
None
Brief Summary:
The hypotheses are 1 the intestinal stem cell marker DCLK1 which is increased in both the epithelium and stroma in colon cancer is also increased in BE Barretts esophagus with HGD high grade dysplasia and in EAC esophageal adenocarcinoma 2 this expression correlates with disease progression towards EAC and 3 eradication of cells expressing stem cell markers occurs after therapy of EMR endoscopic mucosal resection or RFA radiofrequency ablation to eradicate BE with HGD and intramucosal adenocarcinoma and esophagectomy for EAC We will test our hypotheses with the following aims 1 To characterize the cell specific expression patterns of intestinal stem cell biomarkers in BE patients and correlate them with serum expression and disease progression 2 To examine prospectively the effects of EMR RFA or esophagectomy on the expression of stem cell biomarkers and the progression to EAC
Detailed Description:
Barretts esophagus BE is a metaplasia of normal squamous epithelium BE can progressively develop more abnormal features like low-grade intraepithelial dysplasia LGID high-grade intraepithelial dysplasia HGID before ultimately developing esophageal adenocarcinoma EAC with a low 5-year survival rate of 20 or less Recent evidence for the existence of cancer stem cells CSCs has advanced our understanding of cancer and has opened doors to new therapeutic strategies in cancer treatment The fundamental goals of this project are to determine the effectiveness of endoscopic mucosal resection EMR and radiofrequency ablation RFA on eradication of putative intestinal stem cell markers that are overexpressed in BE with HGID and EAC A better understanding of the cellular mechanisms that regulate the progression from normal squamous mucosa to EAC has enormous implications in the diagnosis and treatment of esophageal cancer The presence of a CSC in esophageal cancer has been reported in both dysplastic BE EAC as well as in mouse models of the disease The central hypotheses of the current proposal are elimination of cells expressing stem cell markers occurs after ablative therapies EMRRFA to eradicate BE with HGID EAC and monitoring of stem cell marker expression during follow-up will correlate with disease recurrence or appropriate clinical response Recently we have reported that DCLK1 although minimally expressed in normal distal esophageal squamous mucosa is markedly expressed in BE epithelium and EAC We will test our central hypotheses with the following specific aims 1 To prospectively characterize the cell specific expression patterns of putative intestinal stem cell biomarkers in BE patients and correlate them with serumplasma protein expression and disease progression 2 to examine prospectively the effects of EMRRFA on the expression of putative stem cell biomarkers and correlate them with serumplasma protein expression and disease progression andor recurrence and 3 to examine prospectively the effects on EMR RFA on esophageal-related quality of life and dysphagia during the endoscopic intervention period as well as following completion The studies proposed have the potential to offer new insights for both the early diagnosis and monitoring of therapeutic response of future therapies for EAC Moreover these studies may identify novel biomarkers that can aid in the confirmation of HGID and potentially predict disease onset progression andor recurrence Finally these studies have the potential to provide preliminary data that will serve as the rationale for large scale multicenter trials to compare the effectiveness of EMR and RFA in BE with respect to clinical outcome molecular features and effect on putative tumor stem cells The recent identification of DCLK1 as a marker that distinguishes between normal and tumor stem cells in a rodent model of intestinal tumorigenesis lends support for our rationale for examining DCLK1 as a potential mediator of the neoplastic response in BE
Study Oversight
Has Oversight DMC:
None
Is a FDA Regulated Drug?:
False
Is a FDA Regulated Device?:
False
Is an Unapproved Device?:
None
Is a PPSD?:
None
Is a US Export?:
None
Is an FDA AA801 Violation?:
None