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Non-Endoscopic Surveillance for Barrett's Esophagus Following Ablative Therapy

This study is enrolling participants by invitation only.
Sponsor:
Collaborators:
University of Cambridge
Information provided by (Responsible Party):
Nicholas Shaheen, MD, University of North Carolina, Chapel Hill
ClinicalTrials.gov Identifier:
NCT02106910
First received: April 3, 2014
Last updated: November 11, 2014
Last verified: November 2014
  Purpose

Subjects presenting to UNC Hospitals for routine endoscopic surveillance examinations after successful radiofrequency ablation (RFA) of dysplastic Barrett's Esophagus (BE) will be offered enrollment in the study. After informed consent, and the same day as the endoscopic procedure, the subject will undergo administration of the Cytosponge assay. The patient will then undergo routine endoscopic surveillance, using a standard Seattle biopsy surveillance protocol. The Cytosponge will be placed in fixative and shipped to the Fitzgerald laboratory at the University of Cambridge for processing according to their established protocols. Tissue biopsies will undergo standard processing and H&E staining, with assessment by expert gastrointestinal pathologists at UNC. The primary outcome variables will be sensitivity and specificity of the novel assay, compared against the gold standard of the presence of recurrent BE as detected by upper endoscopy with biopsies. Secondary outcomes include acceptability of the nonendoscopic assay to the patient (assessed by a standardized tool, the Impact of Events Scale, as well as a visual analogue scale), and likelihood of assay positivity as a function of amount of residual disease (as measured by Prague criteria).


Condition
Barrett's Esophagus

Study Type: Observational
Study Design: Observational Model: Cohort
Time Perspective: Prospective
Official Title: Non-Endoscopic Surveillance for Barrett's Esophagus Following Ablative Therapy

Further study details as provided by University of North Carolina, Chapel Hill:

Primary Outcome Measures:
  • Cytosponge Acceptability [ Time Frame: 7 days after Baseline ] [ Designated as safety issue: No ]
    Acceptability will be measured the Impact of Events Scale. This widely used scale was developed to assess the distress associated with a specific life event. It includes measures of both the intrusiveness of the event, and any avoidance responses by the subject in response to the event. The scale will be administrated both shortly after, and 7 days after, the sampling. In order to allow the subjects to have time to reflect on the experience and to compare with the EGD, the 7 day measurements will represent the primary acceptability outcome of the study. Secondary acceptability outcomes will include a visual analogue scale of acceptability of the Cytosponge, performed after the Cytosponge is administered. Also, the subject will be asked whether he/she would be willing to repeat the assay, and, assuming similar accuracy between Cytosponge and upper endoscopy, whether he/she would rather undergo surveillance by Cytosponge or standard esophagogastroduodenoscopy (EGD) with biopsies.

  • Cytosponge Performance [ Time Frame: Baseline ] [ Designated as safety issue: No ]
    Operating characteristics (pathology findings, specimen quality) of the cytosponge will be assessed against a gold standard of upper endoscopy with biopsies for endoscopic surveillance in subjects with a history of successful radiofrequency ablation for dysplastic BE.


Biospecimen Retention:   Samples With DNA

Paraffin embedded esophageal tissue samples obtained by the cytosponge.


Estimated Enrollment: 324
Study Start Date: October 2014
Estimated Study Completion Date: May 2019
Estimated Primary Completion Date: May 2019 (Final data collection date for primary outcome measure)
Groups/Cohorts
Dysplastic BE s/p RFA
Patients with Barrett's Esophagus (BE) with low grade dysplasia (LGD) or high grade dysplasia (HGD) and achieved complete eradication of BE via radiofrequency ablation (RFA).

Detailed Description:

Esophageal Adenocarcinoma is a Lethal Cancer with a Rapidly Increasing Incidence. Barrett's Esophagus (BE) is the Strongest Risk Factor for Esophageal Adenocarcinoma. Endoscopic Ablation Induces Reversion of Barrett's Esophagus, and Decreases Progression of Disease. Unfortunately, data demonstrate a risk of recurrence of BE following successful eradication. Recent data published by the candidate and colleagues from the Ablation of Intestinal Metaplasia Containing Dysplasia (AIM Dysplasia) study demonstrate that approximately 25% of subjects who experience successful eradication of dysplastic BE will develop recurrent BE.

Therefore, following successful endoscopic ablation, patients receive ongoing endoscopic surveillance. More recently, a simple, non-endoscopic device, termed the Cytosponge, has been developed for endoscopic screening of subjects at risk for BE. Cytosponge demonstrated a sensitivity of 90% and a specificity of 94% for the detection of BE.

We expect these investigations to lead to a less costly, highly accurate, less invasive and more preferred screening paradigm for the large number of subjects who have undergone endoscopic ablative therapy.

The Cytosponge is a simple, non-endoscopic device developed for endoscopic screening of subjects at risk for Barrett's esophagus (BE) by investigators at the University of Cambridge in the U.K. The Cytosponge is an ingestible gelatin capsule enclosing a compressed spherical polyurethane mesh sponge of 3 cm diameter, the center of which is attached to a string (Astralen, braided synthetic non-absorbable suture) (Figure 1). The capsule and string are swallowed with water. The string is held at the mouth without tension by means of a 7 cm cardboard tab attached to the string, and esophageal peristalsis and gravity move the capsule into the stomach. After 5 minutes (during which the gelatin capsule dissolves and the sponge is liberated), the sponge is withdrawn by gentle traction on the string and as it does so, collects cells from the lining of the esophagus. The sponge is placed in fixative for 48 hours, then the cells are pelleted, and processed into paraffin blocks. The pellets are immunostained with trefoil factor 3, which is interpreted simply as either positive or negative by the presence of any staining.

  Eligibility

Ages Eligible for Study:   18 Years to 80 Years
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Sampling Method:   Non-Probability Sample
Study Population

Subjects with a history of Barrett's Esophagus with dysplasia (high or low grade) who have achieved complete eradication via radiofrequency ablation (RFA) and are returning to clinic for routine surveillance (upper endoscopy with biopsies) of their condition.

Criteria

Inclusion Criteria:

  • Male or female subjects, age 18-80 years,
  • Previous diagnosis of BE with dysplastic LGD or HGD, as evidenced by both classical endoscopic appearance of salmon-colored mucosa in the tubular esophagus, as well as endoscopic biopsies from the involved areas demonstrating columnar metaplasia with goblet cells. The diagnosis of dysplasia must have been confirmed by a second expert pathologist. Previous endoscopic mucosal resection (EMR) of focal nodular HGD or superficial intramucosal cancer (IMC) is allowable, as long as the EMR specimen shows complete resection of any IMC with clear margins, and biopsies following ablation confirm excision of the lesion,
  • A history of complete eradication of both dysplasia and intestinal metaplasia by radiofrequency ablation. Complete eradication is defined as a normal endoscopic appearance of the tubular esophagus, and histologic confirmation by biopsies in 4 quadrants every cm from throughout the length of the previous BE,
  • Ability to discontinue aspirin, clopidogrel, and/or warfarin for 5 days prior and 7 days after procedures,
  • Good general health, with no severely debilitating diseases, active malignancy, or condition that would interfere with study participation.

Exclusion Criteria:

  • History of esophageal stricture precluding passage of the endoscope or sponge,
  • Pregnancy, or planned pregnancy during the course of the study,
  • Any history of esophageal varices, liver impairment of moderate or worse severity (Child's- Pugh class B & C) or evidence of varices noted on any past endoscopy,
  • Any history of esophageal surgery, except for uncomplicated fundoplication, and,
  • History of coagulopathy, with INR>1.3 and/or platelet count of <75,000.
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT02106910

Locations
United States, North Carolina
University of North Carolina at Chapel Hill
Chapel Hill, North Carolina, United States, 27599
Sponsors and Collaborators
University of North Carolina, Chapel Hill
University of Cambridge
Investigators
Principal Investigator: Nicholas Shaheen, MD, MPH UNC-Chapel Hill
  More Information

No publications provided

Responsible Party: Nicholas Shaheen, MD, Professor of Medicine and Epidemiology; Chief, Division of Gastroenterology & Hepatology, University of North Carolina, Chapel Hill
ClinicalTrials.gov Identifier: NCT02106910     History of Changes
Other Study ID Numbers: 13-2618, 1K24DK100548-01
Study First Received: April 3, 2014
Last Updated: November 11, 2014
Health Authority: United States: Institutional Review Board

Keywords provided by University of North Carolina, Chapel Hill:
Barrett's Esophagus
Radiofrequency Ablation

Additional relevant MeSH terms:
Barrett Esophagus
Digestive System Abnormalities
Digestive System Diseases
Esophageal Diseases
Gastrointestinal Diseases

ClinicalTrials.gov processed this record on November 20, 2014