Barrett's EsophagusNCT03526328
DCLK1 as a Marker/Indicator of Stem Cell Response in Barrett's Esophagus/Esophageal Adenocarcinoma
An observational study of Barrett's Esophagus and Esophageal Adenocarcinoma, run by University of Oklahoma at 1 site in United States.
Trial 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 (Barrett's esophagus) with HGD (high grade dysplasia) and in EAC (esophageal adenocarcinoma), 2) this expression correlates with disease progression towards EAC… Read more about this study
- Who is it for?
- Ages 18 to 85 years
- Conditions the study is for
- Barrett's Esophagus, Esophageal Adenocarcinoma
- What is being tested?
- EMR and RFA effect on stem cell marker expression in BE/EAC
- How many people
- 32 participants
- Where
- 1 siteUnited States
- Study dates
- Mar 2013to 13 Aug 2019
- Phase
- Observational
- Are there results?
- None posted in the registry
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 to 85 years
- All sexes
- No healthy volunteers
- Adult, Older adult
Study population: Patients presenting for upper endoscopy to evaluate symptoms or risk factors such as GERD, dyspepsia, or dysphagia with a finding of BE or EAC; treatment with EMR or RFA for BE with HGD, focal intramucosal adenocarcinoma or esophagectomy for EAC.
Who may be able to join
- BE length of 12 cm or less
- presence of non-dysplastic BE on 2 sequential endoscopies or low-grade intraepithelial dysplasia (LGIN), high-grade intraepithelial dysplasia (HGIN) or EAC in BE segment on 2 endoscopies in the previous 6 months
- no signs of metastasis on endoscopic ultrasonography or computerized tomography scan.
Who cannot join
- pre-RFA EMR with cancer at the resection margin
- greater than T1sm1 invasion
- poor differentiation or worse
- angiolymphatic invasion
- esophageal stenosis preventing passage of an 11.3 mm endoscope
- persistent visible lesions after EMR before RFA and invasive cancer on biopsies after EMR pre-RFA.
Trial locations and contacts
1 site in 1 country.
About this study
Official title: Doublecortin Like Kinase-1 as a Marker and Indicator of Treatment Response for Intestinal Stem Cells in Barrett's Esophagus and Progression to Esophageal Adenocarcinoma
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 (Barrett's 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.
Read the detailed description
Barrett's 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 (EMR/RFA) 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 serum/plasma protein expression and disease progression, 2. to examine prospectively the effects of EMR/RFA on the expression of putative stem cell biomarkers and correlate them with serum/plasma protein expression and disease progression and/or 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 and/or 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.
- Conditions
- Barrett's Esophagus, Esophageal Adenocarcinoma
- Being tested
- EMR and RFA effect on stem cell marker expression in BE/EAC
- Keywords
- DCLK1, Serum Biomarker, Barrett's Esophagus, Esophageal Adenocarcinoma, Tumor Stem Cell Marker
- Medical subject headings
- Barrett Esophagus, Adenocarcinoma Of Esophagus
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
EMR and RFA effect on stem cell marker expression in BE/EACOther
Observation of EMR and RFA on the expression of putative stem cell biomarkers and correlate them with serum/plasma protein expression and disease progression and/or recurrence (Barrett's esophagus/ esophageal adenocarcinoma)
| Study group | Role | What they receive |
|---|---|---|
| DCLK1 post BE treatment | Effects of EMR and RFA on the expression of putative stem cell biomarkers and correlate them with serum/plasma protein expression and disease progression and/or recurrence (Barrett's esophagus/ esophageal adenocarcinoma) Receives: Other: EMR and RFA effect on stem cell marker expression in BE/EAC |
What is being measured
The primary outcome is the main question the study is designed to answer.
cell-specific expression patterns of putative intestinal stem cell biomarkers in BE patients; correlation of markers with serum/plasma protein expression and disease progression.
Exploratory; analysis of expression of various markers for Barrett's esophagus and esophogeal adenocarcinoma
Measured: 2 yrs
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted16 May 2018
- Study startMar 2013
- Primary completion13 Aug 2019
- Study completion13 Aug 2019
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (1)Papers the sponsor has linked to this study.
- Other trials for Barrett's EsophagusStudies of the same condition, open and under way.
- More trials run by University of OklahomaThe sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Observational
- Observational model
- Other
- Time perspective
- Prospective
- Enrolment
- 32 participants (actual)
Sponsor and investigators
- Lead sponsor
- University of Oklahoma
- Sponsor type
- University, hospital or other
- Responsible party
- Sponsor
- Investigators
- Ahmed Bolkhir, MD, Principal investigator, University of Oklahoma
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT03526328
- Sponsor's protocol ID
- 1885
- Status last verified
- Mar 2020
- First submitted
- 26 Sep 2013
- Last updated
- 6 Mar 2020
- Results posted
- No
- Data monitoring committee
- Yes
- FDA-regulated drug
- No
- FDA-regulated device
- No
Publications
Vega KJ, May R, Sureban SM, Lightfoot SA, Qu D, Reed A, Weygant N, Ramanujam R, Souza R, Madhoun M, Whorton J, Anant S, Meltzer SJ, Houchen CW. Identification of the putative intestinal stem cell marker doublecortin and CaM kinase-like-1 in Barrett's esophagus and esophageal adenocarcinoma. J Gastroenterol Hepatol. 2012 Apr;27(4):773-80. doi: 10.1111/j.1440-1746.2011.06928.x.
PubMed 21916995
Study at a glance
From the registry record, last updated by the sponsor on 6 Mar 2020. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Doublecortin Like Kinase-1 as a Marker and Indicator of Treatment Response for Intestinal Stem Cells in Barrett's Esophagus and Progression to Esophageal Adenocarcinoma
- ClinicalTrials.gov ID
- NCT03526328
- Acronym / sponsor ID
- 1885
- Conditions
- Barrett's Esophagus, Esophageal Adenocarcinoma
- Keywords
- DCLK1, Serum Biomarker, Barrett's Esophagus, Esophageal Adenocarcinoma, Tumor Stem Cell Marker
- Study type
- Observational
- Recruitment status
- Completed
- Enrolment
- 32 participants (actual)
- Lead sponsor
- University of OklahomaUniversity, hospital or other
- Study start
- Mar 2013
- Primary completion
- 13 Aug 2019 (actual)
- Study completion
- 13 Aug 2019 (actual)
- First posted
- 16 May 2018 (actual)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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 (Barrett's 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
Barrett's 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 (EMR/RFA) 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 serum/plasma protein expression and disease progression, 2. to examine prospectively the effects of EMR/RFA on the expression of putative stem cell biomarkers and correlate them with serum/plasma protein expression and disease progression and/or 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 and/or 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 design
- Observational model
- Other
- Time perspective
- Prospective
- Number of arms
- 1
| Arm | Type | Receives |
|---|---|---|
| DCLK1 post BE treatment | – | Other: EMR and RFA effect on stem cell marker expression in BE/EACEffects of EMR and RFA on the expression of putative stem cell biomarkers and correlate them with serum/plasma protein expression and disease progression and/or recurrence (Barrett's esophagus/ esophageal adenocarcinoma) |
Who may qualify
- Ages
- 18 to 85 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
- Study population
- Patients presenting for upper endoscopy to evaluate symptoms or risk factors such as GERD, dyspepsia, or dysphagia with a finding of BE or EAC; treatment with EMR or RFA for BE with HGD, focal intramucosal adenocarcinoma or esophagectomy for EAC.
Key inclusion criteria (3 listed)
- BE length of 12 cm or less
- presence of non-dysplastic BE on 2 sequential endoscopies or low-grade intraepithelial dysplasia (LGIN), high-grade intraepithelial dysplasia (HGIN) or EAC in BE segment on 2 endoscopies in the previous 6 months
- no signs of metastasis on endoscopic ultrasonography or computerized tomography scan.
Key exclusion criteria (6 listed)
- pre-RFA EMR with cancer at the resection margin
- greater than T1sm1 invasion
- poor differentiation or worse
- angiolymphatic invasion
- esophageal stenosis preventing passage of an 11.3 mm endoscope
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| EMR and RFA effect on stem cell marker expression in BE/EACObservation of EMR and RFA on the expression of putative stem cell biomarkers and correlate them with serum/plasma protein expression and disease progression and/or recurrence (Barrett's esophagus/ esophageal adenocarcinoma) | Other | DCLK1 post BE treatment |
Primary outcome
cell-specific expression patterns of putative intestinal stem cell biomarkers in BE patients; correlation of markers with serum/plasma protein expression and disease progression.
Time frame: 2 yrs
Exploratory; analysis of expression of various markers for Barrett's esophagus and esophogeal adenocarcinoma
Results and safety
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 6 Mar 2020.
- Background: PubMed 21916995Vega KJ, May R, Sureban SM, Lightfoot SA, Qu D, Reed A, Weygant N, Ramanujam R, Souza R, Madhoun M, Whorton J, Anant S, Meltzer SJ, Houchen CW. Identification of the putative intestinal stem cell marker doublecortin and CaM kinase-like-1 in Barrett's esophagus and esophageal adenocarcinoma. J Gastroenterol Hepatol. 2012 Apr;27(4):773-80. doi: 10.1111/j.1440-1746.2011.06928.x.
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Ahmed Bolkhir, MD principal investigator
University of Oklahoma
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
An observational study of Barrett's Esophagus and Esophageal Adenocarcinoma, run by University of Oklahoma at 1 site in United States.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 3 inclusion and 6 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: finished, as of the sponsor's last update on 6 Mar 2020. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in United States. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
Are results available for this study?
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
cell-specific expression patterns of putative intestinal stem cell biomarkers in BE patients; correlation of markers with serum/plasma protein expression and disease progression. (time frame: 2 yrs). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT03526328, which also lists 1 linked publication.
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 6 Mar 2020.