Clinical trial NCT05210049: Non-endoscopic Esophageal Sampling to Detect Barrett's Esophagus and Esophageal Cancer in Veterans
Official title: Non-endoscopic Esophageal Sampling to Detect Barrett's Esophagus and Esophageal Cancer in Veterans
Study type: INTERVENTIONAL
Overall status: UNKNOWN
Phase: NA
Conditions: Barrett Esophagus
GERD
Obesity
Esophageal Cancer
Keywords: Barrett Esophagus
Screening
Lead sponsor: Cleveland VA Medical Research and Education Foundation
Sponsor class: OTHER
Collaborators: name: United States Department of Defense
First posted: 2022-01-27
Enrollment: 125
Sex: ALL
Minimum age (years): 40
Maximum age (years): 85
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
Primary purpose: SCREENING

Brief summary: 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: 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

Eligibility criteria: 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

Primary outcomes:
measure: Sensitivity and Specificity of Esocheck/Esoguard in a Veteran population
timeFrame: Through study completion, up to 2.5 years
Secondary outcomes:
measure: Number/percentage of screened patients with diagnosis of Barrett's esophagus and/or esophageal adenocarcinoma
timeFrame: Through study completion, up to 2.5 years
measure: Cost of two screening strategies
timeFrame: Through study completion, up to 2.5 years
Other outcomes:
Locations:
city: Cleveland
country: United States
facility: Louis Stokes Cleveland VA Medical Center
state: Ohio
Study officials:
affiliation: Louis Stokes Cleveland VA Medical Center
name: Katarina B Greer, MD/MS
role: PRINCIPAL_INVESTIGATOR
References:
citation: 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.
citation: 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.
citation: 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.
citation: 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.