Back to resultsNon-Endoscopic Surveillance for Barrett's Esophagus Following Ablative Therapy
Primary Purpose
Barrett's Esophagus
Status
Completed
Phase
Not Applicable
Locations
United States
Study Type
Interventional
Intervention
Cytosponge
Sponsored by
About this trial
This is an interventional diagnostic trial for Barrett's Esophagus focused on measuring Barrett's Esophagus, Radiofrequency Ablation
Eligibility Criteria
Inclusion Criteria:
- Male or female subjects, age 18-80 years,
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).
- Good general health, with no severely debilitating diseases, active malignancy, or condition that would interfere with study participation.
Exclusion Criteria:
- 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).
- Known bleeding disorder
- 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.
- 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 international normalized ratio (INR) >1.3 and/or platelet count of <75,000.
Sites / Locations
- University of North Carolina at Chapel Hill
Arms of the Study
Arm 1
Arm 2
Arm Type
Experimental
Experimental
Arm Label
Participants with Barrett's and No History of Ablation
Participants with Barrett's and a History of Ablation
Arm Description
Participants with a diagnosis of BE, presenting for routine care endoscopy for surveillance or treatment of their BE.
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).
Outcomes
Primary Outcome Measures
Cytosponge Acceptability by Number of Participants
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.
Mean Post Procedure Pain on the Visual Analog Scale
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.
Willingness to Repeat Cytosponge by Number of Participants
Participants were asked if they would be willing to repeat the Cytosponge, yes/no.
Mean Procedure Preference Rating
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
Cytosponge™ Operating Characteristics
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).
Full Information
NCT ID
NCT02106910
First Posted
April 3, 2014
Last Updated
November 18, 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
1. Study Identification
Unique Protocol Identification Number
NCT02106910
Brief Title
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
2. Study Status
Record Verification Date
July 2020
Overall Recruitment Status
Completed
Study Start Date
October 27, 2014 (Actual)
Primary Completion Date
August 7, 2018 (Actual)
Study Completion Date
August 14, 2018 (Actual)
3. Sponsor/Collaborators
Responsible Party, by Official Title
Sponsor
Name of the 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
4. Oversight
Product Manufactured in and Exported from the U.S.
No
Data Monitoring Committee
No
5. 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).
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.
6. Conditions and Keywords
Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Barrett's Esophagus
Keywords
Barrett's Esophagus, Radiofrequency Ablation
7. Study Design
Primary Purpose
Diagnostic
Study Phase
Not Applicable
Interventional Study Model
Parallel Assignment
Masking
None (Open Label)
Allocation
Non-Randomized
Enrollment
138 (Actual)
8. Arms, Groups, and Interventions
Arm Title
Participants with Barrett's and No History of Ablation
Arm Type
Experimental
Arm Description
Participants with a diagnosis of BE, presenting for routine care endoscopy for surveillance or treatment of their BE.
Arm Title
Participants with Barrett's and a History of Ablation
Arm Type
Experimental
Arm Description
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).
Intervention Type
Device
Intervention Name(s)
Cytosponge
Intervention Description
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
Primary Outcome Measure Information:
Title
Cytosponge Acceptability by Number of Participants
Description
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.
Time Frame
7 days after Baseline
Title
Mean Post Procedure Pain on the Visual Analog Scale
Description
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.
Time Frame
Immediately after Cytosponge removal
Title
Willingness to Repeat Cytosponge by Number of Participants
Description
Participants were asked if they would be willing to repeat the Cytosponge, yes/no.
Time Frame
7 days after Baseline
Title
Mean Procedure Preference Rating
Description
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.
Time Frame
7 days after Baseline
Secondary Outcome Measure Information:
Title
Cytosponge™ Operating Characteristics
Description
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).
Time Frame
Baseline
10. Eligibility
Sex
All
Minimum Age & Unit of Time
18 Years
Maximum Age & Unit of Time
80 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
Inclusion Criteria:
Male or female subjects, age 18-80 years,
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).
Good general health, with no severely debilitating diseases, active malignancy, or condition that would interfere with study participation.
Exclusion Criteria:
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).
Known bleeding disorder
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.
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 international normalized ratio (INR) >1.3 and/or platelet count of <75,000.
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Nicholas Shaheen, MD, MPH
Organizational Affiliation
UNC-Chapel Hill
Official's Role
Principal Investigator
Facility Information:
Facility Name
University of North Carolina at Chapel Hill
City
Chapel Hill
State/Province
North Carolina
ZIP/Postal Code
27599
Country
United States
12. IPD Sharing Statement
Plan to Share IPD
No
Learn more about this trial
Non-Endoscopic Surveillance for Barrett's Esophagus Following Ablative Therapy
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