Cytosponge Adequacy Study Evaluation II

Study Overview
=================
Brief Summary
-----------------
This study will assess the Minimally Invasive Esophageal Cytology Collection System in Patients with Barrett's Esophagus or GERD Symptoms.

Detailed Description
-----------------
This is a cross-sectional study of subjects with Barrett's esophagus (BE) to assess the utility of the Cytosponge device as a non-endoscopic method for collecting surface cells from the esophagus. This study will enroll 2 groups of subjects: 1) Subjects presenting for routine endoscopic BE surveillance examinations (n=120), and 2) Subjects with gastroesophageal reflux disease (GERD) symptoms undergoing upper endoscopy for screening for BE (n=55). After informed consent, and on the same day as the endoscopic procedure, the subject will undergo administration of the Cytosponge device and complete a questionnaire. The subject will then undergo routine upper endoscopy, with assessment of BE (where applicable), and biopsy per accepted surveillance or screening recommendations. The Cytosponge will be placed in fixative and shipped to an accredited pathology laboratory for embedding in paraffin and hematoxylin and eosin (H&E) staining to assess the adequacy of the specimen. Further evaluation of the specimen may be performed using trefoil factor 3 (TFF3). If the Cytosponge tissue specimen is inadequate, the subject will be recalled for a repeat sponge procedure (not endoscopy) 30 days later. Routine care tissue biopsies will undergo standard processing and H&E staining at the home institution, with assessment by expert gastrointestinal pathologists. Subjects will be contacted via phone 7 days (+/- 2 days) after Cytosponge administration to complete additional questionnaires and assess adverse events.

Official Title
-----------------
Assessment of a Minimally Invasive Esophageal Cytology Collection System in Patients With Barrett's Esophagus or GERD Symptoms

Conditions
-----------------
Barrett's Esophagus, GERD

Intervention / Treatment
-----------------
* Device: Cytosponge™ Cell Collection Device


Participation Criteria
=================
Eligibility Criteria
-----------------
Inclusion Criteria: Male or female subjects, age 18 and above. Able to read, comprehend, and complete the consent form. Clinically fit for an endoscopy. a) Previous confirmed diagnosis of Barrett's esophagus with intestinal metaplasia, and Prague classification of at least one circumferential centimeter of BE or a total BE segment length of at least 3 centimeters (C1+ or CXM3+) (BE arm) . OR b) If the subject does not have documented Prague Classification prior to screening, but the PI is convinced that the subject will meet the inclusion criteria based on previous documentation (for instance, mention of long-segment BE, they may enroll the subject in the study at their discretion. The study upper endoscopy must confirm that the subject has C1+ or CXM3+ (BE arm). If (C1+ or CXM3+) is not observed at the time of study endoscopy, the subject may still be enrolled but not included in the data analysis with the BE cohort. The data may be analyzed in a separate cohort. OR c) Self-reported heartburn or regurgitation on at least a monthly basis for at least 6 months (GERD arm). Exclusion Criteria: Individuals with a diagnosis of an oropharynx, esophageal or gastro-esophageal tumor, or symptoms of dysphagia. Any history of esophageal varices, stricture, or prior dilation of the esophagus. Current use of anti-thrombotics (anti-coagulants and anti-platelet drugs) that cannot be safely discontinued for the appropriate drug-specific interval in the peri-administration period. Depending on the particular agent or reason for the anti-thrombotic therapy, it may not be necessary to discontinue anti-thrombotic agents. There could be circumstances where the drug may not need to be discontinued if the risk of bleeding is considered negligible (e.g. daily aspirin therapy). Physicians should use their clinical judgement and should consult guidelines such as those provided by the ASGE. Known bleeding disorder. Individuals who have had a myocardial infarction or any cardiac event < 6 months prior to enrollment. Individuals who have had a cerebrovascular event < 6 months prior to enrollment in which swallowing was affected. Prior ablative or resection therapy of the esophagus including radiofrequency ablation (RFA), photodynamic therapy (PDT), spray cryotherapy, endoscopic mucosal resection, and other ablation therapies. Any history of esophageal surgery, except for uncomplicated fundoplication. Do not need upper endoscopy as part of patient management. Pregnancy

Ages Eligible for Study
-----------------
Minimum Age: 18 Years

Sexes Eligible for Study
-----------------
All

Accepts Healthy Volunteers
-----------------
Accepts Healthy Volunteers

Study Plan
=================
How is the study designed?
-----------------

Design Details

Primary Purpose: Diagnostic
Allocation: Non-Randomized
Intervention Model: Single Group Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Patient wth Barrett's<br>Subjects presenting for routine endoscopic BE surveillance examinations | Device: Cytosponge™ Cell Collection Device<br>* Cytosponge™ Cell Collection Device is indicated for use in the collection and retrieval of surface cells in the esophagus.<br>|
| Experimental: Patients with GERD<br>Subjects with gastroesophageal reflux disease (GERD) symptoms undergoing upper endoscopy for screening for BE | Device: Cytosponge™ Cell Collection Device<br>* Cytosponge™ Cell Collection Device is indicated for use in the collection and retrieval of surface cells in the esophagus.<br>|

What is the study measuring?
-----------------
Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Procedure Preference and Acceptability Questionnaire and Visual Analog Scale | The first primary objective of the study was to assess the acceptability of a novel, minimally invasive esophageal mucosal sampling technique, the Cytosponge™, in subjects undergoing surveillance of BE who have had at least a C1 or M3 segment confirmed, and 2) in subjects with GERD undergoing screening for BE. This includes measures of acceptability as demonstrated on the Impact of Event Scale, a Visual Analog Scale for Pain, and the subject's willingness to undergo repeat Cytosponge™ administration if it were offered to him/her. The Visual Analog Scale is measured from 0-100 scale for pain, 0 representing no pain and 100 representing the highest level of pain. | Immediately post procedure up to 7 days +/- 3 days | 
| Number of Participants With Adequate Cytosponge™ Sample | To assess the adequacy of cytology samples obtained by Cytosponge in this population after 1 sampling, and after 2 samplings if first sample inadequate. | Immediately post procedure up to 7 days +/- 3 days | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Operating Characteristics | The operating characteristics of this technique against a gold standard of upper endoscopy with biopsies for endoscopic surveillance in subjects with BE who demonstrate an adequate sample on Cytosponge assessment. | Immediately post procedure up to 7 days +/- 3 days | 
| Cytosponge™ Operating Characteristics vs Worst Histology Ever | The second secondary objective was to assess the operating characteristics of Cytosponge™ against the worst ever histology documented in the subject. | Immediately post procedure up to 7 days +/- 3 days | 
| Cytosponge™ Operating Characteristics as a Function of Baseline Histology | The third secondary objective was to assess the operating characteristics of Cytosponge™ as a function of baseline histology. At the outset of this study, no data was available regarding the accuracy of TFF3 in samples collected by Cytosponge™ in subjects with BE and more advanced disease (low-grade dysplasia and high-grade dysplasia). These subjects are at greatest risk for progression to cancer. We planned to collect pilot data on operating characteristics of the assay by degree of baseline dysplasia. We hypothesized that TFF3 would perform with similar operating characteristics in this group compared to non-dysplastic BE. | Immediately post procedure up to 7 days +/- 3 days | 
| Summary of Abrasion, Bleeding, and Perforation Observed Via Endoscopy | The fourth secondary objective was to assess the degree of mucosal abrasion following Cytosponge™ administration, using a standardized scale. The incidence is presented in the data below for abrasion, bleeding and perforation observed during Endoscopy. | Immediately post procedure up to 7 days +/- 3 days | 
| Ongoing Safety Measures | To collect and analyze ongoing safety measures of Cytosponge use in the target population. | Immediately post procedure up to 7 days +/- 3 days |