Clinical trial NCT00288119: Genetic Determinants of Barrett's Esophagus and Esophageal Adenocarcinoma
Official title: Genetic and Environmental Determinants of Barrett's Esophagus and Esophageal Adenocarcinoma
Study type: OBSERVATIONAL
Overall status: RECRUITING
Conditions: Barrett's Esophagus
Esophageal Neoplasm
Keywords: Barrett's Esophagus
Lead sponsor: Case Western Reserve University
Sponsor class: OTHER
Collaborators: name: University Hospitals Cleveland Medical Center
name: Washington University School of Medicine
name: Fred Hutchinson Cancer Center
name: University of Washington
name: Mercy Medical Center
name: Johns Hopkins University
name: Mayo Clinic
name: University of North Carolina, Chapel Hill
name: The Cleveland Clinic
name: University of Pennsylvania
name: Columbia University
name: VA Puget Sound Health Care System
First posted: 2006-02-07
Enrollment: 2000
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: yes
Observational model: CASE_CONTROL
Time perspective: CROSS_SECTIONAL
Sampling method: NON_PROBABILITY_SAMPLE
Study population: Individuals with Barrett's esophagus or adenocarcenoma of the esophagus whose medical care is at the participating institutions, are referred from outside institutions, or who contact the participating institutions.

Brief 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.

Detailed 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.

Eligibility criteria: 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.

Primary outcomes:
measure: Assay of DNA and RNA markers
timeFrame: 1 week
Secondary outcomes:
measure: Score of tolerability and acceptability
timeFrame: 1 minute after procedure
Other outcomes:
Locations:
city: Baltimore
country: United States
facility: Johns Hopkins Hospital
state: Maryland
city: Rochester
country: United States
facility: Mayo Clinic
state: Minnesota
city: Saint Louis
country: United States
facility: Washington University School of Medicine
state: Missouri
city: New York
country: United States
facility: Columbia University Medical Center
state: New York
city: Chapel Hill
country: United States
facility: University of North Carolina at Chapel Hill
state: North Carolina
city: Cleveland
country: United States
facility: University Hospitals of Cleveland
state: Ohio
city: Cleveland
country: United States
facility: Cleveland Clinic
state: Ohio
city: Philadelphia
country: United States
facility: University of Pennsylvania
state: Pennsylvania
city: Seattle
country: United States
facility: VA Puget Sound Health Care System
state: Washington
city: Seattle
country: United States
facility: Fred Hutchinson Cancer Research Center, UWMC
state: Washington
Study officials:
affiliation: University Hospitals Cleveland Medical Center, CWRU, Cleveland, OH
name: Amitabh Chak, MD
role: PRINCIPAL_INVESTIGATOR
affiliation: University of Pennsylvania
name: Gary W Falk, MD, MS
role: PRINCIPAL_INVESTIGATOR
affiliation: Fred Hutchinson Cancer Research Center, UWMC, Seattle, WA
name: William Grady, MD
role: PRINCIPAL_INVESTIGATOR
affiliation: University of North Carolina, Chapel Hill
name: Nicholas J Shaheen, M.D.
role: PRINCIPAL_INVESTIGATOR
affiliation: Mayo Clinic
name: Ganapathy Prasad, M.D.
role: PRINCIPAL_INVESTIGATOR
affiliation: Johns Hopkins University
name: Marcia Canto, M.D.
role: PRINCIPAL_INVESTIGATOR
affiliation: University Hospitals Cleveland Medical Center
name: John Dumont, D.O.
role: PRINCIPAL_INVESTIGATOR
affiliation: The Cleveland Clinic
name: Prashanthi Thota, M.D.
role: PRINCIPAL_INVESTIGATOR
affiliation: Washington University School of Medicine
name: Jean Wang, MD
role: PRINCIPAL_INVESTIGATOR
affiliation: Columbia University
name: Julian Abrams, MD
role: PRINCIPAL_INVESTIGATOR
affiliation: VA Puget Sound Health Care System
name: Andrew Kaz, MD
role: PRINCIPAL_INVESTIGATOR
References:
citation: 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.
citation: Chak A, Chen Y, Vengoechea J, Canto MI, Elston R, Falk GW, Grady WM, Guda K, Kinnard M, Markowitz S, Mittal S, Prasad G, Shaheen N, Willis JE, Barnholtz-Sloan JS. Variation in age at cancer diagnosis in familial versus nonfamilial Barrett's esophagus. Cancer Epidemiol Biomarkers Prev. 2012 Feb;21(2):376-83. doi: 10.1158/1055-9965.EPI-11-0927. Epub 2011 Dec 16.