Genetic Determinants of Barrett's Esophagus and Esophageal Adenocarcinoma

Barrett's Esophagus Clinical Trial

— FBE  

Official title:

Genetic and Environmental Determinants of Barrett's Esophagus and Esophageal Adenocarcinoma

Clinical Trial Details — Status: Recruiting

Administrative data

• NCT number: NCT00288119
• Other study ID #: R01DK070863
• Secondary ID: NIH IK24DK02800
• Status: Recruiting
• Start date: October 1, 2005
• Est. completion date: July 31, 2028

Study information

• Verified date: May 2024
• Source: Case Western Reserve University
• Contact: Amitabh Chak, MD
• Phone: 216-844-5385
• Email: axc22[@]po.cwru.edu
• Is FDA regulated: No
• Study type: Observational

Clinical Trial Summary

The overall objectives of this BETRNet Research Center (RC) are:

1. to conduct a rigorous, integrated spectrum of transdisciplinary human research in Barrett's esophagus (BE) and esophageal adenocarcinoma (ECA)

2. to increase the biological understanding of key observations made by our clinical researchers;

3. to translate knowledge derived from genetic, epigenetic, and transcriptome research to solving clinical dilemmas in detection, prognosis, prevention, and therapy of BE in order to prevent EAC and improve the outcomes of EAC;

4. to foster a transdisciplinary and translation research culture and to effectively expand and enhance scientific research focused on BE and EAC;

5. to evaluate research and transdisciplinary programs and to continuously improve research, productivity and enhance translational implementation. These objectives build and synergize on existing multi-institutional collaborative networks and the considerable clinical, basic science, and translational expertise available at our institutions, focusing on improving the outcomes of patients with BE and EAC. The overarching organization framework for this RC proposal is 1) to focus laboratory research on understanding the genetic susceptibility, genomic and epigenetic changes that influence the development of BE and EAC; and 2) to then translate laboratorydiscoveries into clinical applications for effective detection, molecular risk stratification, and prevention of progression from BE to EAC.

Description:

This research will eventually lead to the identification of inherited genetic changes that cause Barrett's esophagus and esophageal cancer. It will help the investigators develop better methods for preventing or identifying esophageal cancer at an early curable stage.

The capsule can be swallowed with a few sips water. Once the capsule is advanced to 45-50 cm from the incisors and reaches the stomach the balloon is inflated to a size of 16 mm with 5.5 cc air. It is withdrawn until a tug is felt to locate the gastroesophageal junction (GEJ). The inflated balloon is then pulled back 3 to 5 cm to sample the distal esophagus, then completely deflated to cause inversion of the biospecimen into its protective capsule, and then withdrawn. The balloon is re-inflated outside the patient and the obtained sample is clipped with scissors into a vial and frozen. The collected biospecimen will be stored frozen for later DNA extraction and assay. The vials will be labeled with a coded sample number. In a pilot study of 120 subjects this capsule esophageal sampling was performed with no adverse events reported. Similar esophageal sampling devices have been reported on over 1600 patients with no adverse events.

All patients will also undergo standard EGD. Patients with BE or EAC will have standard of care surveillance and diagnostic biopsies. All cases and controls will have research esophageal brushings from the BE/EAC and distal esophagus/gastric cardia, respectively. Cases and controls will also obtain research brushings from the proximal normal squamous esophagus. Research mucosal biopsies will also be obtained from the BE and EAC epithelium as well as normal stomach and duodenum in cases and from the gastric cardia and the distal squamous esophagus as well as normal stomach and duodenum in controls. Biopsies from BE and EAC will be directed by using high definition narrow band imaging. Biospecimens, brushings and biopsies, will be snap frozen at bedside and stored for future research assays. Although we do not anticipate any problems with our non-endoscopic balloon screening, these archived pathology samples and snap frozen samples will be available for assay in case we fail to detect our markers in patients with BE diagnosed at EGD or experience a high false positive rate. Subjects who undergo non-endoscopic sampling of the distal esophagus will be asked questions that rate their discomfort on a Likert scale and also asked questions comparing the non-endoscopic sampling study with an EGD.

Other known NCT identifiers

• NCT00058877

Recruitment information / eligibility

• Status: Recruiting
• Enrollment: 2000
• Est. completion date: July 31, 2028
• Est. primary completion date: July 31, 2028
• Accepts healthy volunteers: Accepts Healthy Volunteers
• Gender: All
• Age group: 18 Years and older

Eligibility

Eligible cases will be defined as those patients and their family members who meet the following criteria:

• Barrett's esophagus confirmed by review of pathology and endoscopy report or adenocarcinoma of the esophagus or family members of person with Barrett's esophagus or adenocarcinoma of the esophagus.

• Male or female age 18 or older at time of enrollment or male or female less than 18 years of age at time of enrollment with parental consent.

• Ability to give informed consent, if patient is age 18 or older.

Related Conditions & MeSH terms

• Adenocarcinoma
• Barrett Esophagus
• Barrett's Esophagus
• Esophageal Neoplasm
• Esophageal Neoplasms

Intervention

Device:
• Balloon Capsule Device
The Esophageal Sampling Device BESD-001 is a non-endoscopic balloon capsule catheter for obtaining an esophageal mucosal sample. At the distal end of the catheter there is a silicone capsule textured balloon assembly. The textured balloon is initially inverted with vacuum for patient to swallow the capsule but then is inflated with 5.6 cc of air (5 cc syringe withdrawn maximally) to a 16-18 mm diameter in order to contact the lumen of the esophagus to collect a sample. The balloon has a textured surface, which enhances the collection of the esophageal sample. Following sample collection the textured balloon is inverted back into the hollow capsule component via syringe draw vacuum in order to maximize & protect the site-specific sample collection.

Procedure:
• Endoscopy
An upper endoscopy is a procedure used to visually examine your upper digestive system with a tiny camera on the end of a long, flexible tube.

Locations

Country	Name	City	State
United States	Johns Hopkins Hospital	Baltimore	Maryland
United States	University of North Carolina at Chapel Hill	Chapel Hill	North Carolina
United States	Cleveland Clinic	Cleveland	Ohio
United States	University Hospitals of Cleveland	Cleveland	Ohio
United States	Columbia University Medical Center	New York	New York
United States	University of Pennsylvania	Philadelphia	Pennsylvania
United States	Mayo Clinic	Rochester	Minnesota
United States	Washington University School of Medicine	Saint Louis	Missouri
United States	Fred Hutchinson Cancer Research Center, UWMC	Seattle	Washington
United States	VA Puget Sound Health Care System	Seattle	Washington

Sponsors (13)

Lead Sponsor	Collaborator
Case Western Reserve University	Columbia University, Fred Hutchinson Cancer Center, Johns Hopkins University, Mayo Clinic, Mercy Medical Center, The Cleveland Clinic, University Hospitals Cleveland Medical Center, University of North Carolina, Chapel Hill, University of Pennsylvania, University of Washington, VA Puget Sound Health Care System, Washington University School of Medicine

Country where clinical trial is conducted

United States, 

References & Publications (1)

Douville C, Moinova HR, Thota PN, Shaheen NJ, Iyer PG, Canto MI, Wang JS, Dumot JA, Faulx A, Kinzler KW, Papadopoulos N, Vogelstein B, Markowitz SD, Bettegowda C, Willis JE, Chak A. Massively Parallel Sequencing of Esophageal Brushings Enables an Aneuploidy-Based Classification of Patients With Barrett's Esophagus. Gastroenterology. 2021 May;160(6):2043-2054.e2. doi: 10.1053/j.gastro.2021.01.209. Epub 2021 Jan 22. — View Citation

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Assay of DNA and RNA markers	The Balloon tip is collected and sent to the PacificDx Laboratory in Irvine California to test for DNA extraction	1 week
Secondary	Score of tolerability and acceptability	6 item scale rating scale using scale of 1-10 where 1 is no worries to 10 being severe to rate Tolerability; and a 3 item scale rating the acceptability of Balloon Capsule Device using strongly agree to strongly disagree rating	1 minute after procedure