Non-endoscopic Esophageal Sampling to Detect Barrett's Esophagus and Esophageal Cancer in Veterans

NCT ID: NCT05210049

Last Updated: 2022-12-15

Study Results

Results pending

The study team has not published outcome measurements, participant flow, or safety data for this trial yet. Check back later for updates.

Basic Information

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Recruitment Status

UNKNOWN

Clinical Phase

NA

Total Enrollment

125 participants

Study Classification

INTERVENTIONAL

Study Start Date

2022-03-01

Study Completion Date

2024-08-31

Brief Summary

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This study seeks to incorporate non-endoscopic detection method (Esocheck/Esoguard) in primary care practice and test whether this screening modality increases the positive predictive value of upper endoscopy and increases the detection of Barrett's esophagus and esophageal cancer.

Detailed Description

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This study addresses prevention and early detection of esophageal adenocarcinoma (EAC). Prospectively collected Surveillance Epidemiology and End Results (SEER) data indicate that the incidence of esophageal adenocarcinoma (EAC) has increased more than 6-fold in the past four decades. The prognosis for patients with EAC is poor with less than 20% of patients surviving beyond 5 years. The veteran population is at increased risk for EAC and its precursor lesion, Barrett's esophagus (BE), due to increased prevalence of disease risk factors including advanced age, gastroesophageal reflux, caucasian race, male sex, smoking history, and obesity compared to the general population. Research has shown that veterans often present with an advanced cancer stage, despite opportunities to screen for BE in veterans with known risk factors. Therefore, there is an urgent clinical need to improve strategies for the detection and prevention of BE and EAC.

Currently, BE is diagnosed only when patients undergo endoscopy with esophagogastroduodenoscopy (EGD). However, due to the high cost of EGD and the lack of a randomized controlled trials supporting its efficacy, endoscopy to screen for BE is not routinely recommended. Current guidelines do recommend sedated EGD in patients with multiple BE risk factors, refractory GERD, or alarm symptoms. This strategy fails to detect BE in patients whose symptoms are well controlled with either over the counter medications or physician prescribed therapies. It also fails to detect BE in asymptomatic subjects who comprise 40% of those that develop EAC. Thus, less than 10% of esophageal adenocarcinomas are diagnosed as early stage lesions caught by surveillance of patients with previously detected BE. Ablative non-surgical therapies that have been developed for preventing cancer in patients with BE with high grade dysplasia over the past decade will have little impact and the 5 year survival for esophageal adenocarcinomas will remain a dismal 18% unless more effective programs for identifying BE and early EAC are developed.

The main hypothesis of this study is that incorporation of a non-endoscopic detection method in primary care practice will increase the positive predictive value of EGD and increase the detection of BE.

The objective of this study is to incorporate a novel unsedated BE screening method for veterans at risk for EAC into a primary care practice at a VA hospital.

Esocheck/Esoguard is a FDA approved device designed to sample the distal esophagus and analyze the collected material for presence of two methylated DNA markers.

The Specific Aims of this study are:

1. To determine sensitivity, specificity, positive and negative predictive value of Esocheck/Esoguard performed in routine practice for detecting BE in an at risk Veteran population
2. To compare the yield of detected BE using EGD alone vs. stepwise molecular diagnostics(Esocheck/Esoguard) and endoscopic screening strategy (EGD) in at risk Veteran population

Conditions

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Barrett Esophagus GERD Obesity Esophageal Cancer

Keywords

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Barrett Esophagus Screening

Study Design

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Allocation Method

NA

Intervention Model

SINGLE_GROUP

Primary Study Purpose

SCREENING

Blinding Strategy

NONE

Study Groups

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Patients undergoing routine screening via upper endoscopy (EGD)

All enrolled patients will complete upper endoscopy for screening for Barrett's esophagus and esophageal adenocarcinoma.

Group Type OTHER

Esocheck/Esoguard

Intervention Type DIAGNOSTIC_TEST

All enrolled patients will complete the Esocheck screening test. EsoCheck is a cell collection device that is designed to collect cells of a targeted region of the esophagus. The collected cell material is examined with a two marker panel combining methylated CCNA1 and VIM. These methylated markers have 95% sensitivity and 91% specificity for detecting BE and EAC with an AUC=0.95 in studies performed among white men. Diagnostic yield of this test among Veterans is unknown.

Interventions

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Esocheck/Esoguard

All enrolled patients will complete the Esocheck screening test. EsoCheck is a cell collection device that is designed to collect cells of a targeted region of the esophagus. The collected cell material is examined with a two marker panel combining methylated CCNA1 and VIM. These methylated markers have 95% sensitivity and 91% specificity for detecting BE and EAC with an AUC=0.95 in studies performed among white men. Diagnostic yield of this test among Veterans is unknown.

Intervention Type DIAGNOSTIC_TEST

Eligibility Criteria

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Inclusion Criteria

Patients who have symptomatic GERD and also meet criteria for upper endoscopic screening for BE will be accrued. Eligible patients will include:

1. Adult Veterans \> 40 and \< 85 years old who have no prior EGD and can provide informed consent
2. No known coagulopathy, no known esophageal varices.
3. No significant dysphagia or odynophagia
4. Documented GERD or use of proton pump inhibitors (PPIs) for \> 5 years
5. Meet ACG Clinical Guideline criteria for BE screening (that require presence of multiple risk factors 21). Eligible subjects to qualify must have will have GERD plus at least two additional risk factors for BE (white race, obesity defined as BMI \> 30, male gender, smoking history, family history).

Exclusion Criteria

1. Patients with known coagulopathy (INR \> 1.5) will be excluded
2. Patients with known esophageal varices will be excluded.
3. Patients with significant dysphagia (unable to swallow solids) or odynophagia will be excluded
Minimum Eligible Age

40 Years

Maximum Eligible Age

85 Years

Eligible Sex

ALL

Accepts Healthy Volunteers

No

Sponsors

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United States Department of Defense

FED

Sponsor Role collaborator

Louis Stokes VA Medical Center

FED

Sponsor Role lead

Responsible Party

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Responsibility Role SPONSOR

Principal Investigators

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Katarina B Greer, MD/MS

Role: PRINCIPAL_INVESTIGATOR

Louis Stokes Cleveland VA Medical Center

Locations

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Louis Stokes Cleveland VA Medical Center

Cleveland, Ohio, United States

Site Status RECRUITING

Countries

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United States

Central Contacts

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Jeffrey Moore, PhD

Role: CONTACT

Phone: 216-791-2300

Email: [email protected]

Marcie Denallo, BS

Role: CONTACT

Phone: (216) 791-2300

Email: [email protected]

Facility Contacts

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Katarina B Greer, MD

Role: primary

Andrew Blum, MD/PhD

Role: backup

References

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Grady WM, Yu M, Markowitz SD, Chak A. Barrett's Esophagus and Esophageal Adenocarcinoma Biomarkers. Cancer Epidemiol Biomarkers Prev. 2020 Dec;29(12):2486-2494. doi: 10.1158/1055-9965.EPI-20-0223. Epub 2020 Oct 22.

Reference Type BACKGROUND
PMID: 33093162 (View on PubMed)

Kaz AM, Wong CJ, Luo Y, Virgin JB, Washington MK, Willis JE, Leidner RS, Chak A, Grady WM. DNA methylation profiling in Barrett's esophagus and esophageal adenocarcinoma reveals unique methylation signatures and molecular subclasses. Epigenetics. 2011 Dec;6(12):1403-12. doi: 10.4161/epi.6.12.18199.

Reference Type BACKGROUND
PMID: 22139570 (View on PubMed)

Moinova HR, LaFramboise T, Lutterbaugh JD, Chandar AK, Dumot J, Faulx A, Brock W, De la Cruz Cabrera O, Guda K, Barnholtz-Sloan JS, Iyer PG, Canto MI, Wang JS, Shaheen NJ, Thota PN, Willis JE, Chak A, Markowitz SD. Identifying DNA methylation biomarkers for non-endoscopic detection of Barrett's esophagus. Sci Transl Med. 2018 Jan 17;10(424):eaao5848. doi: 10.1126/scitranslmed.aao5848.

Reference Type BACKGROUND
PMID: 29343623 (View on PubMed)

Tan WK, Sharma AN, Chak A, Fitzgerald RC. Progress in Screening for Barrett's Esophagus: Beyond Standard Upper Endoscopy. Gastrointest Endosc Clin N Am. 2021 Jan;31(1):43-58. doi: 10.1016/j.giec.2020.08.004.

Reference Type BACKGROUND
PMID: 33213799 (View on PubMed)

Greer KB, Blum AE, Faulx AL, Deming EM, Hricik LL, Siddiqui H, Wilson BM, Chak A. Nonendoscopic Screening for Barrett's Esophagus and Esophageal Adenocarcinoma in At-Risk Veterans. Am J Gastroenterol. 2025 Mar 1;120(3):545-553. doi: 10.14309/ajg.0000000000002962. Epub 2024 Jul 11.

Reference Type DERIVED
PMID: 38989889 (View on PubMed)

Other Identifiers

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1641950-1

Identifier Type: -

Identifier Source: org_study_id