Clinical trial NCT02106910: Non-Endoscopic Surveillance for Barrett's Esophagus Following Ablative Therapy
Official title: Non-Endoscopic Surveillance for Barrett's Esophagus Following Ablative Therapy
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: NA
Conditions: Barrett's Esophagus
Keywords: Barrett's Esophagus
Radiofrequency Ablation
Lead sponsor: University of North Carolina, Chapel Hill
Sponsor class: OTHER
Collaborators: name: University of Cambridge
name: National Institutes of Health (NIH)
name: National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK)
name: Medtronic
First posted: 2014-04-08
Enrollment: 138
Sex: ALL
Minimum age (years): 18
Maximum age (years): 80
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NON_RANDOMIZED
Intervention model: PARALLEL
Primary purpose: DIAGNOSTIC

Brief summary: Subjects presenting to University of North Carolina at Chapel Hill (UNC) Hospitals for routine endoscopic surveillance examinations for current Barrett's Esophagus (BE) or 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 Hematoxylin and Eosin (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).

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 capsule enclosing a compressed spherical mesh sponge of 3 cm diameter, the center of which is attached to a string. The capsule and string are swallowed with water. The string is held at the mouth without tension by means of a cardboard tab attached to the string, and esophageal peristalsis and gravity move the capsule into the stomach. After 5 minutes (during which the 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, 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 criteria: Inclusion Criteria:

1. Male or female subjects, age 18-80 years,
2. Meets the following:

   2.1. Previous diagnosis of Barrett's Esophagus (BE) with dysplastic low grade dysplasia (LGD) or high grade dysplasia (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 high grade dysplasia (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, AND 2.1.1. 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 (post-RFA cohort).OR 2.2. Current diagnosis of BE, presenting for routine care endoscopy (BE cohort).
3. Good general health, with no severely debilitating diseases, active malignancy, or condition that would interfere with study participation.

Exclusion Criteria:

1. Current use of blood thinners such as coumadin, warfarin, clopidogrel, heparin and/or low molecular weight heparin (requires discontinuation of medication 5 days prior to and 7 days after esophagogastroduodenoscopy (EGD) and Cytosponge administration, aspirin use is OK).
2. Known bleeding disorder
3. For the post-RFA cohort, prior ablative therapy of the esophagus other than radiofrequency ablation (RFA), including photodynamic therapy (PDT), more than one session of spray cryotherapy, and any other ablation therapies is exclusionary. However, prior endoscopic mucosal resection (EMR) is acceptable and up to two prior treatments of thermal/coagulation therapy (other than RFA) for focal residual disease following otherwise successful RFA therapy is acceptable.
4. History of esophageal stricture precluding passage of the endoscope or sponge,
5. Pregnancy, or planned pregnancy during the course of the study,
6. 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,
7. Any history of esophageal surgery, except for uncomplicated fundoplication, and,
8. History of coagulopathy, with international normalized ratio (INR) \>1.3 and/or platelet count of \<75,000.

Primary outcomes:
measure: Cytosponge Acceptability by Number of Participants
timeFrame: 7 days after Baseline
measure: Mean Post Procedure Pain on the Visual Analog Scale
timeFrame: Immediately after Cytosponge removal
measure: Willingness to Repeat Cytosponge by Number of Participants
timeFrame: 7 days after Baseline
measure: Mean Procedure Preference Rating
timeFrame: 7 days after Baseline
Secondary outcomes:
measure: Cytosponge™ Operating Characteristics
timeFrame: Baseline
Other outcomes:
Locations:
city: Chapel Hill
country: United States
facility: University of North Carolina at Chapel Hill
state: North Carolina
Study officials:
affiliation: UNC-Chapel Hill
name: Nicholas Shaheen, MD, MPH
role: PRINCIPAL_INVESTIGATOR
References: