|Principal Investigator: John Fang|
|Keywords: EsoGuard , EsoCheck , EGD , Barrett's Esophagus , Esophageal Adenocarcinoma , Esophagogastroduedonoscopy Alternative||Department: Gastroenterology|
|IRB Number: 00131631|
|Specialty: Gastroenterology, Gastroenterology, Gastroenterology, Gastroenterology|
|Sub Specialties: Esophageal Diseases, Barrett's Esophagus, Endoscopy|
|Recruitment Status: Not yet recruiting|
Lucid Diagnostics, Inc., is developing a novel diagnostic system as a screening tool for Barrett’s Esophagus (BE) consisting of two devices, EsoCheck, a non-invasive cell collection device designed to sample cells from a targeted region of the esophagus, and EsoGuard, an assay which examines for the presence of cytosine methylation at 31 different genomic locations on the VIM and CCNA1 genes. The combined system may offer an accurate, lower cost, non-invasive, approach to screen for BE with and without dysplasia, and for esophageal adenocarcinoma (EAC), as compared with the current gold standard, namely diagnostic esophagogastroduodenoscopy (EGD) plus biopsy.
This is a two-phase Case-Control study. A Run-In phase will be conducted in order to derive numerical cutoffs for mVIM and mCCNA1 scoring as inputs into an algorithm used to determine a positive versus negative EsoGuard result in order to optimize assay sensitivity and specificity for its intended use as a screening test in the at-risk population. The assay, once validated and locked, will be used to analyze patient biospecimens obtained in both the Efficacy phase of this Case Control study as well as in a separate Screening study to be conducted in parallel. The Efficacy phase is intended to estimate the sensitivity of EsoGuard, on samples collected using EsoCheck, to diagnose each of four subgroups of BE, including non-dysplastic BE (NDBE), BE with low grade dysplasia (LGD), BE with high grade dysplasia (HGD), and EAC (specifically esophageal intramucosal adenocarcinoma [IMC]) in a population of known Cases, independently against prespecified performance goals. Specificity will be estimated in a group of concurrent Controls confirmed to be free of these conditions.
The objective of the Run-in Phase is to derive numerical cutoffs for mVIM and mCCNA1 scoring as inputs into an algorithm used to determine a positive versus negative EsoGuard result, in order to optimize assay sensitivity and specificity for its intended use as a screening test in the at-risk population. The assay, once validated and locked, will be used to analyze patient biospecimens obtained in both the Efficacy phase of this Case Control study as well as in a separate Screening study to be conducted in parallel.
Primary: The primary efficacy objectives of this study are to measure the sensitivities of EsoGuard-based diagnosis in
54 cases each of NDBE, LGD, HGD, and intramucosal adenocarcinoma (IMC) in order to assess EsoGuard’s ability to detect disease across the entire continuum of disease progression.
Secondary: The Secondary efficacy objective is to quantify the specificity in 54 concurrent Controls without BE, dysplasia or IMC.
1. Men aged 50 years and above (Inclusion exclusion criteria for this protocol are based on the ACG 2015 Clinical Guideline. "The criteria by which the ACG 2015 guidance defines an individual to be at high risk for BE and EAC, and thus indicated for BE screening, are men with chronic and/or frequent symptoms of GERD plus at least 2 of the following: age >50; Caucasian race; central obesity; current or past history of smoking; first-degree relative with BE or EAC)
2. ≥5 years either of
GERD treated with proton pump inhibitor (PPI) therapy (whether symptom control is achieved or not), or
any combination of treated and untreated periods, as long the cumulative total is at least 5 years
3. No solid foods eaten for at least 2 hours prior to EsoCheck procedure
4. One or more of the following:
Current or past history of chronic smoking
Body mass index (BMI) of at least 30 kg/m2
First-degree relative with BE or EAC
1. Previous diagnosis of NDBE, LGD, HGD, and/or IMC
2. Diagnosis by EGD (with exception of NDBE) was within 4 months prior to study enrollment
3. Indicated for surveillance EGD or for therapeutic EGD
4. Able to provide, by day of study EGD, the original glass slide(s) of biopsy specimens from most recent prior EGD
Rationale for #1 (males):
Male gender is another consistently identified risk factor for BE and EAC. A meta-analysis for BE demonstrated an overall pooled male:female ratio of 2:1.
The risk of progression to EAC is also significantly higher in men. In a study using the Surveillance, Epidemiology, and End Results (SEER) database, 88% of EACs were in men.
The criteria by which the ACG 2015 guidance defines an individual to be at high risk for BE and EAC, and thus indicated for BE screening, are men with chronic and/or frequent symptoms of GERD plus at least 2 of the following: age >50; Caucasian race; central obesity; current or past history of smoking; first-degree relative with BE or EAC.
Increasing age is a risk factor for BE. In a retrospective study using the CORI (Clinical Outcomes Research Initiative) database, the yield of BE in white men with GERD was 2% in the third decade of life but increased to 9% in the sixth decade.
The mean age of onset of EAC is almost 70 years old, and while BE, dysplasia, and EAC all do occur in people below the age of 50 years, the societal cost-effectiveness from screening a population below this age is prohibitive.
1. Inability to provide written informed consent
2. On anti-coagulant drug(s) that cannot be temporarily discontinued
3. Known history of esophageal varices or esophageal stricture
4. Any contraindication, as deemed in Investigator’s medical judgment, to undergoing the EsoCheck procedure, undergoing the EGD procedure, and/or having biopsies taken, including but not limited to due to comorbidities such as coagulopathy or a known history of esophageal diverticula, esophageal fistula, and/or esophageal ulceration
5. History of difficulty swallowing (dysphagia) or painful swallowing (odynophagia), including swallowing pills
6. Oropharyngeal tumor
7. History of esophageal or gastric surgery, with exception of uncomplicated surgical fundoplication procedure
8. History of myocardial infarction or cerebrovascular accident within past 6 months
9. Any known lesion which, in the opinion of the endoscopist, obstructs greater than 25% of the esophageal lumen
10. Prior participation in PR-0139/EG-CL-101 (Lucid BE Screening Study)
11. Prior EGD during which a therapeutic procedure such as, but not limited to, ablation, cryotherapy or endoscopic mucosal resection, was performed for the treatment of BE and/or EAC