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

• ClinicalTrials.gov Identifier: NCT02106910
• Recruitment Status: Completed
• First Posted: April 8, 2014
• Results First Posted: November 20, 2020
• Last Update Posted: November 20, 2020
• Sponsor: University of North Carolina, Chapel Hill
• Collaborators: University of Cambridge; National Institutes of Health (NIH); National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK); Medtronic
• Information provided by (Responsible Party): University of North Carolina, Chapel Hill

Study Description

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).

Condition or disease	Intervention/treatment	Phase
Barrett's Esophagus	Device: Cytosponge	Not Applicable

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.

Study Design

• Study Type: Interventional (Clinical Trial)
• Actual Enrollment: 138 participants
• Allocation: Non-Randomized
• Intervention Model: Parallel Assignment
• Masking: None (Open Label)
• Primary Purpose: Diagnostic
• Official Title: Non-Endoscopic Surveillance for Barrett's Esophagus Following Ablative Therapy
• Actual Study Start Date: October 27, 2014
• Actual Primary Completion Date: August 7, 2018
• Actual Study Completion Date: August 14, 2018

Arms and Interventions

Arm	Intervention/treatment
Experimental: Participants with Barrett's and No History of Ablation; Participants with a diagnosis of BE, presenting for routine care endoscopy for surveillance or treatment of their BE.	Device: Cytosponge; 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 to 7 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
Experimental: Participants with Barrett's and a History of Ablation; Participants 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).	Device: Cytosponge; 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 to 7 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

Outcome Measures

Primary Outcome Measures :

1. Cytosponge Acceptability by Number of Participants [ Time Frame: 7 days after Baseline ]
   Acceptability will be measured the Impact of Events Scale (IES). This scale was developed to assess the distress associated with a specific life event. Respondents are asked to answer questions to indicate the amount of stress from the event. Scores are calculated with the following scale, (Not at all =0, Rarely =1, Sometimes =3, Often =5). Assessment yields a cumulative score that are calculated from each response, with a total final score ranging from (0-75). High scores represent high test induced distress and lower values represent low distress.
2. Mean Post Procedure Pain on the Visual Analog Scale [ Time Frame: Immediately after Cytosponge removal ]
   The visual analog scale (VAS) is a validated, subjective measure for acute and chronic pain. Scores are recorded by making a handwritten mark on a 100-mm line that represents a continuum between "no pain" and "worst pain." Higher scores are representative of worse pain.
3. Willingness to Repeat Cytosponge by Number of Participants [ Time Frame: 7 days after Baseline ]
   Participants were asked if they would be willing to repeat the Cytosponge, yes/no.
4. Mean Procedure Preference Rating [ Time Frame: 7 days after Baseline ]
   Participants were asked to rate both procedures (Cytosponge and esophagogastroduodenoscopy (EGD)) to indicate which procedure they preferred on a scale from 0-10. Higher scores represent greater preference.

Secondary Outcome Measures :

1. Cytosponge™ Operating Characteristics [ Time Frame: Baseline ]
   The operating characteristics of the Cytosponge™ technique compared against a gold standard of upper endoscopy with biopsies for endoscopic surveillance was evaluated for sensitivity and specificity in the detection of BE in subjects with current (BE) or history of successful radiofrequency ablation for dysplastic BE. A true positive was considered when both the endoscopic biopsy and the Cytosponge detected the goblet cells characteristic of BE. A false positive was considered when the Cytosponge demonstrated these cells while the biopsies did not. A true negative occurred when neither the biopsies nor the Cytosponge showed goblet cells. A false negative was considered when the biopsies did demonstrate goblet cells while the Cytosponge did not. True Positives (TP) and False Negatives calculate sensitivity: (TP)/(TP + FN); True Negatives (TN) and False Positives (FP) are used to calculate specificity: (TN)/(TN + FP).

Eligibility Criteria

• Ages Eligible for Study: 18 Years to 80 Years (Adult, Older Adult)
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: No

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.

Contacts and Locations

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

National Institutes of Health (NIH)

National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK)

Medtronic

Investigators

• Principal Investigator: Nicholas Shaheen, MD, MPH; UNC-Chapel Hill

  Study Documents (Full-Text)

Documents provided by University of North Carolina, Chapel Hill:

Study Protocol and Statistical Analysis Plan  [PDF] December 8, 2015

More Information

• Responsible Party: University of North Carolina, Chapel Hill
• ClinicalTrials.gov Identifier: NCT02106910
• Other Study ID Numbers: 13-2618; 1K24DK100548-01 ( U.S. NIH Grant/Contract )
• First Posted: April 8, 2014
• Results First Posted: November 20, 2020
• Last Update Posted: November 20, 2020
• Last Verified: July 2020

Individual Participant Data (IPD) Sharing Statement:

• Plan to Share IPD: No

• Product Manufactured in and Exported from the U.S.: No

Keywords provided by University of North Carolina, Chapel Hill:

Barrett's Esophagus; Radiofrequency Ablation

Additional relevant MeSH terms:

Barrett Esophagus; Precancerous Conditions; Neoplasms; Esophageal Diseases; Gastrointestinal Diseases; Digestive System Diseases