Assessment of a Minimally Invasive Esophageal Cytology Collection System in Patients With Barrett's Esophagus or GERD Symptoms
Phase: NA
Conditions: Barrett's Esophagus, GERD
Sponsor: Medtronic - MITG

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Version G 01-DEC-2017 
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Clinical Investigation Plan 
Clinical Investigation Plan/Study Title  ASSESSMENT OF A MINIMALLY INVASIVE 
ESOPHAGEAL CYTOLOGY COLLECTION SYSTEM IN 
PATIENTS WITH BARRETT’S ESOPHAGUS OR GERD 
SYMPTOMS (CASE II)  
Clinical Investigation Plan Identifier COVB2710467 
Study Product Name 
&\WRVSRQJH&HOO&ROOHFWLRQ'HYLFH
 
Sponsor/Local Sponsor Medtronic MITG RGI Gastrointestinal & 
Hepatology 
540 Oakmead Parkway, Sunnyvale, CA 94085 
 
 
Document Version G, 01-DEC-2017 
Lead Principal Investigator(s) Nicholas J. Shaheen, MD, MPH 
Professor of Medicine and Epidemiology
Chief, Division of Gastroenterology & Hepatology 
University of North Carolina School of Medicine 
Chapel Hill, NC  
Confidentiality Statement 
The information contained in this document is confidential and the proprietary property of Medtronic. 
Any distribution, copying, or disclosure without the prior written authorization of Medtronic is strictly 
prohibited. Persons to whom the information is disclosed must know that it is confidential and that it 
may not be further disclosed by them. 
 

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Study product Name 
&\WRVSRQJH&HOO&ROOHFWLRQ'HYLFH 
Sponsor
Medtronic MITG RGI Gastrointestinal & Hepatology 
 
540 Oakmead Parkway, Sunnyvale, CA 94085 
 
Clinical Investigation Plan Identifier 
COVB2710467 
Version Number/Date  
G, 01-DEC-2017 
I have read the protocol, including all appendices, and I agree that it contains all necessary details for me 
and my staff to conduct this study as described. I will conduct this study as outlined herein and will make 
a reasonable effort to complete the study within the time designated. 
I agree to comply with International Conference on Harmonization Guidelines on Good Clinical Practice, 
ISO 14155:2011 (Clinical Investigation of Medical Devices for Human Subjects-GCP), United States Food 
and Drug Administration regulations, and any regional or national regulations, as appropriate. I agree to 
ensure that the confidential information contained in this document will not be used for any purpose 
other than the evaluation and conduct of the clinical investigation without the prior written consent of 
Medtronic. 
 
I will provide all study personnel under my supervision copies of the protocol and access to all 
information provided by Medtronic. I will discuss this material with them to ensure that they are fully 
informed about the products and the study. 
 
Investigator’s Signature: 
 
 
Investigator’s Name: 
 
 
Institution: 
 
 
Date:  
 
 
 

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Term 
Definition 
AE 
Adverse event 
BE 
Barrett's esophagus 
C1 
One circumferential centimeter of BE 
eCRF 
Electronic case report form 
EAC 
Esophageal adenocarcinoma 
GERD 
Gastroesophageal reflux disease  
H&E 
Hematoxylin and eosin 
HGD 
High-grade dysplasia 
HIPAA 
Health Insurance Portability and Accountability 
IRB 
Institutional review board 
LGD 
Low-grade dysplasia 
M3 
A total BE segment length of at least three 
centimeters 
MedDRA 
Medical dictionary for regulatory activities 
PDT 
Photodynamic therapy 
PHI 
Protected health information 
RFA 
Radiofrequency ablation 
TFF3 
Trefoil factor 3 
VAS 
Visual analog scale 

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Title 
ASSESSMENT OF A MINIMALLY INVASIVE ESOPHAGEAL CYTOLOGY 
COLLECTION SYSTEM IN PATIENTS WITH BARRETT’S ESOPHAGUS OR 
GERD SYMPTOMS (CASE II)  
Clinical Study Type 
 U.S. Pilot Study 
Product Name 
&\WRVSRQJH&HOO&ROOHFWLRQ'HYLFH
Sponsor  
Medtronic MITG RGI Gastrointestinal & Hepatology 
540 Oakmead Parkway, Sunnyvale, CA 94085 
 
Indication under 
investigation  
Post-market approval
Investigation Purpose 
To assess the utility of the Cytosponge device as a non-endoscopic 
method for collecting surface cells from the esophagus in patients with 
BE and GERD 
Product Status 
510(k) clearance 
Primary Objective(s) 
x
To assess the acceptability of a novel, minimally invasive 
esophageal mucosal sampling technique, the Cytosponge 1) in 
subjects undergoing surveillance of BE who have had at least a 
C1 or M3 segment confirmed (or medically suspected), and 2) 
in subjects with GERD undergoing screening for BE  Patients 
who are undergoing ablative therapy on the day of Cytosponge 
testing will have their acceptability data analyzed separately.   
Based on previous data, we hypothesize that the sponge-based 
sampling technique will be associated with low levels of subject 
distress, and will be preferred by subjects, when compared to 
standard sedated upper endoscopy, for surveillance of their 
esophageal mucosa. 
 
 
1) To assess the adequacy of cytology samples obtained by 
Cytosponge in this population after 1 sampling, or after 2 
samplings if first sample is inadequate.   
Based on previous data, we hypothesize that the Cytosponge 
will harvest adequate amounts of esophageal cells to perform 
centrifugation, pelleting, sectioning and staining for trefoil 
factor 3, a reliable biomarker of intestinal metaplasia. 
Secondary Objective(s) 
1) To assess 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.  

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2) To assess the operating characteristics of Cytosponge against 
the worst ever histology documented in the subject.  Patients 
who are undergoing ablative therapy on the day of Cytosponge 
testing must have biopsies within 2 months prior to surgery.   
Because Cytosponge provides a “field” sampling of esophageal 
tissue, it may provide a more comprehensive assessment of 
minute fields of dysplasia.  If this is so, the Cytosponge may 
avoid sampling error associated with random clinical samples as 
currently performed.    
 
3) To assess the operating characteristics of Cytosponge on the 
basis of baseline histology.   
To date, no data is available regarding the accuracy of 
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 plan to collect 
pilot data on operating characteristics of the assay by degree of 
baseline dysplasia. We hypothesize that Cytosponge will 
perform with similar operating characteristics in this group 
compared to non-dysplastic BE. 
 
4) To assess the degree of mucosal abrasion following Cytosponge 
administration, using a standardized scale.  
Based on previous data, we hypothesize that mucosal damage 
due to abrasion by the Cytosponge will be minor. Further, the 
distal extent of the abrasion will correlate with the presence of 
columnar cells in the sample. 
 
5) To collect and analyze safety measures of Cytosponge use in 
the target population. 
The Cytosponge has been found to be safe and well-tolerated 
when administered in a primary care setting.  We will continue 
collecting safety data as part of this project. All AEs will be 
coded using the Medical Dictionary for Regulatory Activities 
(MedDRA). 
Study Design 
Multicenter, cross-sectional clinical trial 
Sample Size
Up to 275 subjects with an enrollment ratio of at least >50% BE and 
>25% GERD  
Inclusion/Exclusion Criteria 
Inclusion Criteria: 
1) Male or female subjects, age 18 and above. 
2) Able to read, comprehend, and complete the consent form. 
3) Clinically fit for an endoscopy. 

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4) 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: 
1) Individuals with a diagnosis of an oropharynx, esophageal or 
gastro-esophageal tumor, or symptoms of dysphagia. 
2) Any history of esophageal varices, stricture, or prior dilation of 
the esophagus. 
3) 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.   
4) Known bleeding disorder. 
5) Individuals who have had a myocardial infarction or any cardiac 
event < 6 months prior to enrollment. 
6) Individuals who have had a cerebrovascular event < 6 months 
prior to enrollment in which swallowing was affected. 
7) Prior ablative or resection therapy of the esophagus including 
radiofrequency ablation (RFA), photodynamic therapy (PDT), 
spray cryotherapy, endoscopic mucosal resection, and other 
ablation therapies.   
8) Any history of esophageal surgery, except for uncomplicated 

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fundoplication. 
9) Do not need upper endoscopy as part of patient management. 
 
10)Pregnancy 
 
Study Procedures and 
Assessments 
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 or planned ablation 2) 
Subjects with gastroesophageal reflux disease (GERD) symptoms 
undergoing upper endoscopy for screening for BE.  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 and a visual analog pain scale (VASThe subject will then 
undergo routine upper endoscopy, with assessment of BE (where 
applicable), and routine care biopsies will be taken per accepted 
surveillance or screening recommendations by performing physician. 
Photographs of the distal esophagus are encouraged to be taken. For 
subjects presenting for GERD, a single set of 4 quadrant biopsies (4 
pieces of tissue total) of the gastric cardia (TGF+1) will be collected 
during the endoscopy procedure.  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 will be performed using trefoil factor 3 (TFF3).  If the 
Cytosponge tissue specimen is inadequate, the subject will be recalled 
for a repeat sponge procedure.  All study-specific gastric cardia 
biopsies, as well as any routine care tissue biopsies will undergo 
standard processing and H&E staining at the home institution, with 
assessment by gastrointestinal pathologists. Subjects will be contacted 
via phone 7 days (+/-3 days) after Cytosponge administration to 
complete additional questionnaire and assess adverse events. 
Safety Assessments 
Adverse events will be reported by number, severity, and relationship 
to the study procedures and devices.  The Medical Monitor will 
adjudicate all serious adverse events, unanticipated adverse device 
effects, and events determined by the reporting investigators to be 
related to the device (possible, probable, definite and unable to be 
determined). 

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Statistics 
For the first primary objective, to assess the acceptability of the 
Cytosponge in subjects with BE, we will assess the distribution of 
Impact of Event Scale scores, and the intrusiveness and avoidance 
subscales. We will generate measures of central tendency and 
distribution of these data. Bivariate analysis will be performed to assess 
predictors of low tolerance of Cytosponge surveillance, and a logistic 
regression model will be created to assess these factors while 
controlling for potential confounders. Data will be compared to 
population norms in published literature1 using parametric statistics.  
Visual analog scale (VAS) scores will be calculated, and measures of 
central tendency and distribution reported. 
Subjects’ preferences for Cytosponge versus endoscopic surveillance, as 
well as willingness to undergo the procedure again, will be measured as 
proportions, with bivariate and multivariate analyses for predictors of 
preference performed.  Subjects who undergo same day ablative 
therapy will Impact of Event Scale scores evaluated separately.   
 
For the second primary objective, to assess the adequacy of samples, 
sample adequacy will be treated as a dichotomous variable.  For 
purposes of this investigation, an adequate sample will be one in which 
at least 1 columnar cell is present.  Sample adequacy will be presented 
as a proportion of subjects who fulfill this definition after up to 2 total 
administrations of the Cytosponge, as noted in the methods. 
 
For the first three secondary objectives, to assess the operating 
characteristics of Cytosponge against various gold standards, initially 
2x2 tables will be constructed demonstrating Cytosponge and the gold 
standard findings (Y/N for BE). Both endoscopic evidence of BE of C1 or 
CXM3 or greater length and pathological confirmation of specialized IM 
(intestinal metaplasia with goblet cells) will be used in the final 
diagnosis of BE. Sensitivity, specificity, positive predictive value, 
negative predictive value and accuracy will be calculated. Because 
Cytosponge positivity may vary based on the burden of BE, we will 
perform sensitivity analyses, defining “positive” cases as those with BE 
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disease burden on operating characteristics. Multivariate models 
controlling for age, sex, burden of disease, and other potential 
confounders will be constructed, to assess the impact of these factors 

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on test accuracy. Although we do not expect to see an association 
between the degree of dysplasia and Cytosponge positivity, exploratory 
analyses will be performed using degree of dysplasia as a predictor 
variable, and Cytosponge positivity as the outcome variable. For the 
fourth secondary objective, to assess the degree of mucosal abrasion 
following Cytosponge, endoscopic abrasion scores will be correlated 
with the presence of columnar cells on the H&E slide made from the 
Cytosponge samples. 
To assess safety (fifth secondary objective), the number and percentage 
of subjects with adverse events related to Cytosponge administration 
will be summarized by MedDRA system organ class and preferred term 
overall, and by severity. 
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Barrett’s esophagus (BE) is a premalignant condition associated with the development of esophageal 
adenocarcinoma (EAC). BE is the replacement of the normal (squamous) lining of the lower esophagus 
with a glandular lining which more closely resembles the intestine.  BE is a relatively common condition, 
affecting 1-2% of the general adult population. In the majority of such patients, the condition will be 
indolent and EAC will not develop. However, in <5% of these patients, BE will progress to EAC. 
Progression to BE is thought to occur through worsening degrees of dysplasia: from no dysplasia, to low-
grade dysplasia (LGD), to high-grade dysplasia (HGD), to EAC. The prognosis of EAC is dismal, with a five-
year survival <15%. For that reason, endoscopic surveillance is suggested in patients with BE to monitor 
development and progression of dysplasia.  
Traditional screening and surveillance endoscopy is not optimal due to cost issues, inter-observer 
variability in histology interpretation, and biopsy sampling error. In addition, surveillance endoscopies 
expose the patient to recurrent risks associated with sedation and upper endoscopy, the inconvenience 
of these exams, as well as the associated financial burden.   
Cytosponge is a minimally invasive, sponge-based technique for sampling the esophageal mucosa.
 
 
 
 
 
 

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This is a comparative effectiveness study to assess the utility of the Cytosponge in endoscopic 
surveillance or treatment of patients with BE, as well as screening of patients with gastroesophageal 
reflux disease (GERD) symptoms. The central hypothesis of this study is that this novel surveillance tool 
could supplant upper endoscopy in patients with BE, providing less invasive and more cost-effective 
surveillance of this large and growing patient population. 
 3XUSRVH
EAC is a lethal cancer with a rapidly increasing 
incidence.  In stark contrast to recent progress in 
treating other solid tumors, incidence and death 
rates from EAC continue to rise rapidly in the U.S. 
There has been a 500% increase in the incidence of 
EAC from the 1970s to the 1990s,3 and a near-
parallel increase in mortality (Figure 1),  
underscoring the need for more effective 
prevention and treatment for this lethal cancer. 
Esophageal adenocarcinoma is thought to develop 
through a series of metaplastic, then dysplastic, 
changes of the mucosa.4 GERD precipitates a 
metaplastic change from the normal squamous epithelium, to 
a more acid-resistant columnar histology.5 When this 
columnar epithelium contains goblet cells, it is termed 
specialized or intestinalized metaplasia. When endoscopically evident, columnar metaplasia with  goblet 
cells in the esophagus is termed BE. 
BE is the strongest risk factor for EAC. BE is associated with a risk of EAC that is 40-120 times that of the 
general population.8,9 Furthermore, BE is an extremely common condition, present in approximately 
10% of patients with chronic GERD10 and in 1-2% of the general population.11 Since 10-20% of adult 
Americans have at least weekly symptoms of GERD,12,13 the number of cases of BE in the U.S. is thought 
to be >2 million. BE does not generally spontaneously regress; barring an intervention, the patient will 
have BE for life. Most patients harboring BE will not progress to EAC. However, in a proportion (0.2-
0.5%/year,)14 the metaplastic tissue will progress from LGD to HGD, culminating in EAC.15,16 Given the 
poor prognosis of cancer diagnosed symptomatically,17,18 current effort is directed toward early 
detection and treatment. Current strategies for prevention of EAC focus on endoscopic screening and 
surveillance.19 In the approach most commonly used in the U.S., patients with chronic heartburn are 
Figure 1 Incidence (top curve) and 
associated mortality (lower) of EAC25 

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offered a screening endoscopy to assess for BE. Patients found to have BE are then enrolled in 
endoscopic surveillance, consisting of periodic endoscopy at intervals governed by the presence of 
dysplasia.6 In current American College of Gastroenterology guidelines,6 patients with nondysplastic BE 
should undergo endoscopic surveillance no more frequently than every 3–5 years. Patients with BE and 
LGD are to undergo endoscopic eradication therapy, or, as an alternative, have surveillance endoscopy 
yearly. Patients with BE and HGD are effectively managed with endoscopic therapy.20. Endoscopic exams 
for GERD and BE are common and costly, with over 330,000 exams/year in Medicare patients alone,21 
and an average total cost in ambulatory care centers of >$2,000/exam, making for $660M in endoscopy 
costs in the Medicare population alone annually.22  
A novel non-endoscopic technique as a potential 
surveillance tool for patients with BE.  Given the large 
number of patients with chronic GERD and BE, and the 
expense and inconvenience of endoscopic examinations 
for BE, investigators have sought less expensive, non-
endoscopic modalities of assessing patients for BE. Early 
attempts using a non-endoscopic balloon demonstrated 
inadequate sensitivity, in part due to inadequate 
cytological samples.23  
Medtronic Gastrointestinal and Hepatology (formerly 
Medtronic GI Solutions), has developed a more refined 
version of the Cytosponge I (referred hereafter as the 
CytospongeTM or “Cytosponge”). The Cytosponge was 
developed from the Cytosponge I specification and 
design, with the additional priority of a more 
reproducible manufacturing process, standardization of dimensions, and other quality related features 
(Figure 2). Because we seek to assess a tool for widespread clinical usage, this study will use the 
Cytosponge provided by Medtronic GIH Solutions 
 
 
 
 
 
 
 
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The following 2 primary objectives will be assessed: 
1. 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. Based on 
previous data, we hypothesize that the sponge-based sampling technique will be associated 
with low levels of subject distress, and will be preferred by subjects, when compared to 
standard sedated upper endoscopy, for surveillance of their esophageal mucosa. 
 
2. To assess the adequacy of cytology samples obtained by Cytosponge in this population after 1 
sampling, and after 2 samplings if first sample inadequate. Based on previous data, we 
hypothesize that the Cytosponge will harvest adequate amounts of esophageal cells to perform 
centrifugation, pelleting, sectioning and staining for TFF3, a reliable biomarker of intestinal 
metaplasia. 
 
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The following 5 secondary objectives will be assessed: 
x
To assess 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.  
 
x
To assess the operating characteristics of Cytosponge against the worst ever histology 
documented in the subject.  Because Cytosponge provides a “field” sampling of esophageal 
tissue, it may provide a more comprehensive assessment of minute fields of dysplasia.  If this is 
so, the Cytosponge may avoid sampling error associated with random clinical samples as 
currently performed. Patients who are undergoing ablative therapy on the day of Cytosponge 
testing must have biopsies within 2 months prior to treatment.   
 

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To assess the operating characteristics of Cytosponge as a function of baseline histology.  To 
date, no data are available regarding the yield of 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 plan to collect pilot data on operating characteristics of the 
assay by degree of baseline dysplasia. We hypothesize that Cytosponge will perform with similar 
operating characteristics in this group compared to non-dysplastic BE. 
 
x
To assess the degree of mucosal abrasion following Cytosponge administration, using a 
standardized scale. Based on previous data, we hypothesize that mucosal damage due to 
abrasion by the Cytosponge will be minor.  Further, the distal extent of the abrasion will 
correlate with the presence of columnar cells in the sample. 
 
x
To collect and analyze ongoing safety measures of Cytosponge use in the target population. The 
Cytosponge has been found to be safe and well-tolerated when administered in a primary care 
setting.  We will continue collecting safety data as part of this project.  All AEs will be coded 
using MedDRA.  
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The primary endpoint variables will be acceptability of the Cytosponge as demonstrated on the Impact 
of Event Scale, a visual analog scale, as well as the subject’s willingness to undergo repeat Cytosponge 
administration if it were offered to him/her.  Additionally, we will assess the adequacy of the sample, as 
defined above.  

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Secondary endpoints include the sensitivity, specificity, positive predictive value and negative predictive 
value of Cytosponge both overall, and stratified by baseline histology and length of BE. The presence of 
BE will be defined as per ACG guidelines, with histology interpreted by the home institution. Additional 
secondary outcomes include degree of mucosal abrasion and safety data.  
6WXG\'HVLJQ
This is a cross-sectional study of subjects with BE to assess the utility of the Cytosponge device as a non-
endoscopic method for sampling surface cells from the esophagus. Patients presenting for routine 
endoscopic BE surveillance examinations, planned ablation or examinations investigating chronic GERD 
symptoms will be offered enrollment in the study. After informed consent, and on the same day as the 
planned standard of care endoscopic procedure, the subject will undergo administration of the 

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Cytosponge device and then complete questionnaires. The subject will then undergo standard of care 
upper endoscopy with or without biopsy. The biopsy protocol will be performed according to accepted 
recommendations.  For subjects presenting for GERD, a single set of 4 quadrant biopsies (4 pieces of 
tissue total) of the gastric cardia (TGF+1) will be collected during the endoscopy procedure.  If for some 
reason a biopsy is not taken, the subject will still count toward enrollment and their data will be used in 
the final data set. It is encouraged for Investigators to take photos of the gastroesophageal junction 
(GEJ) during the endoscopy procedure.  
 
The Cytosponge will be placed in fixative and shipped to an accredited pathology laboratory for 
processing 
 will provide results on each sample.  Cardia 
biopsies and routine care tissue biopsies will undergo standard processing and hematoxylin and eosin 
(H&E) staining at the home institutions, with assessment by expert pathologists. Subjects will be 
contacted via phone 7 days (+/-3days) after Cytosponge administration to complete an additional 
questionnaire and assess adverse events.  For quality assurance, Cytosponge samples may be sent to the 
 to be processed and read, as needed to optimize training at the central lab.  
These results will be compared to those reported by 
.  If the results are conflicting, 
 
training may be revisited and consensus read will be used. 
If the initial administration of the Cytosponge demonstrates an inadequate sample, defined as a sample 
that does not demonstrate at least one columnar cell on H&E staining, repeat Cytosponge 
administration will be performed. 
Subject recruitment will be from consecutive eligible patients presenting for surveillance endoscopy for 
BE or planned ablative or upper endoscopy for investigation of chronic GERD symptoms, either 
medicated or un-medicated with acid-suppressive therapy.  Potentially eligible patients will be 
contacted by telephone in advance of their procedure and their interest in study participation assessed. 
Patients interested in participating will be asked to present to the endoscopy unit at least two hours 
(may vary by site) prior to their scheduled procedure.  At that time, inclusion and exclusion criteria will 
be reviewed, and eligible patients will give informed consent. Subjects will then undergo Cytosponge 
administration. Following Cytosponge administration, subjects will complete a questionnaire and pain 
scale. Subjects will then attend their scheduled endoscopy session. Upper endoscopy will be performed 
and biopsies are required to be taken as part of routine care.  For subjects presenting for GERD, a single 
set of 4 quadrant biopsies (4 pieces of tissue total) of the cardia will be collected during the endoscopy 
procedure and will be specific to this research study.  The research-specific gastric cardia biopsies will be 
taken in addition to any routine care biopsies, if applicable, and will still be obtained even if routine care 
biopsies are not taken during the procedure. The Sponsor will pay for any charges related to collection 
and pathology of the research specific gastric cardia biopsies.  It is encouraged for Investigators to take 
photos of the gastroesophageal junction (GEJ) during the endoscopy procedure.  

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All study-specific gastric cardia biopsies, as well as any routine care tissue biopsies will undergo standard 
processing and H&E staining at the home institution, with assessment by expert gastrointestinal 
pathologists. The Sponsor will pay for any charges incurred for collection and pathology assessment of 
the study-specific gastric cardia biopsies. 
Enrolled subjects will be administered the Cytosponge one time, on the date of an endoscopy scheduled 
for routine care, prior to the endoscopy. Subjects can only participate one time. The only exception is for 
subjects who have an inadequate sample on the initial Cytosponge.  These subjects will be asked to 
return for repeat Cytosponge administration after the initial administration. 
All subjects taking part in the study will be undergoing an endoscopy as part of standard of care, the 
risks of the study are all linked with the administration of the Cytosponge, and are extremely low as no 
Cytosponge I related serious adverse events have been reported in subjects from the BEST1 study 
(n=504) and/or BEST2 (to date n= 1500)2.  
The results from this study will not be used to influence patient management or follow-up.  
 'XUDWLRQ
Participation in the study may last about4-10 days after the procedure. Subjects will be contacted 7 days 
(+/- 3 days) following the Cytosponge and upper endoscopy procedures. During this phone call, adverse 
events will be assessed and subjects will complete final questionnaire.  Participation in the study is 
complete when subjects have completed the follow-up phone call. 
If the Cytosponge tissue specimen is reported as inadequate by the central pathologist, the subject will 
be asked to return for repeat Cytosponge administration. Only the Cytosponge™ Cell Collection capsule 
administration will be repeated. Questionnaires and the endoscopy procedure will not be repeated. 
The study is expected to last a total of 24 months (2 years).  
 5DWLRQDOH
A simple, non-endoscopic device, termed the Cytosponge I, has been developed for endoscopic 
screening of patients at risk for BE by investigators at the University of Cambridge in the U.K. The 
Cytosponge I is an ingestible gelatin capsule enclosing a compressed spherical mesh 3 cm in diameter, 
the center of which is attached to a string (Figure 3).  The capsule and string are swallowed with water. 
The string is held at the mouth without tension, allowing the capsule to move into the stomach. After 7-
10 minutes (during which the gelatin capsule dissolves and the sponge is liberated), the sponge is 
withdrawn by gentle traction on the string. The sponge is placed in fixative for 48 hours, then the cells 
are pelleted, and processed into paraffin blocks. The pellets are immunostained with an antibody for 
trefoil factor 3 (TFF3), which is present within goblet cells thus defining the presence of specialized 

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intestinal metaplasia. TFF3 is interpreted in a binary fashion, i.e., either positive or negative. In a recent 
study of 504 subjects with chronic GERD symptoms in the U.K. who underwent both Cytosponge analysis 
and upper endoscopy, the Cytosponge demonstrated a sensitivity of 90% and a specificity of 94% for the 
detection of BE (Prague classification C2 or more).2 Follow-up work with an additional 334 subjects (186 
controls, 148 BE) demonstrated similar results, with a sensitivity of 84% and a specificity of 92% (data 
courtesy of Rebecca Fitzgerald, MA (Cantab) MD). These results suggest the Cytosponge may be suitable 
to serve as a surveillance tool in patients with BE, as well as a screening tool in patients with chronic 
reflux symptoms. 
Dr. Fitzgerald and colleagues administered the Cytosponge I to 504 subjects in a primary care setting 
and found it to be safe and well-tolerated. Of these subjects, 501 (99%) were able to successfully 
swallow the capsule.  Unsurprisingly, given pill-swallowing difficulty in the general population, 3 subjects 
were unable to swallow the pill, feeling it was too large. No adverse events were noted, and subjects 
demonstrated a low level of anxiety associated with the test.2  A second study published by the same 
investigators, BEST2, administered the Cytosponge I to an additional 831 subjects in a multicenter, 
prospective design. An interim data analysis demonstrated a similarly excellent safety and tolerance 
profile, with no serious adverse events reported.24 Overall, to date, there have been 1,335 documented 
administrations of the sponge, with few adverse events reported.  Several hundred additional uses of 
the device have occurred in Cambridge, U.K., without significant adverse events (personal 
communication, Dr. Fitzgerald), but have not yet been reported in the peer-reviewed literature.  
3URGXFW'HVFULSWLRQ
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The Cytosponge™ Cell Collection Device (Cytosponge) is intended to collect surface cells from the 
esophagus.  The device consists of a swallowable capsule, which dissolves in the body cavity, releasing a 
self-expandable sponge.  The sponge is then retrieved from the esophagus using an attached string. 
During the retrieval process, the sponge collects cells from the most superficial layer of the esophageal 
mucosa.  Once removed from the patient, the sponge and cells are retained for investigation and/or 
testing.  
The Cytosponge™ Cell Collection Device (Cytosponge) received 510(k) clearance from the FDA on 
November 26, 2014 (K142695). The Cytosponge ™ Cell Collection device is a Class II product under 21 
CFR 874.4710 esophagoscope (flexible or rigid) and accessories. The sponsor has determined clinical 
study COVB2710467 entitled - Assessment Of A Minimally Invasive Esophageal Cytology Collection 
System In Patients With Barrett’s Esophagus Or GERD Symptoms is a Non-Significant Risk (NSR) Device 
study based on “Information Sheet Guidance for IRBs, Clinical Investigators, and Sponsors – Significant 
Risk and Non-significant Risk Medical Device Studies” published by the FDA (January 2006).  

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The CytospongeTM device (referred to hereafter as the 
“Cytosponge”) will be supplied by Medtronic to the 
participating sites. Study sites will be responsible for 
storage and accountability of the device. The 
Cytosponge lifetime/use by date will be confirmed on 
the product packaging. The device received FDA 510(k) 
clearance on November 26, 2014 (K142695).
 
 
 
  
  Cytosponge administration will occur after an 
overnight fast to minimize the possibility of aspiration 
of any gastric contents. Every administered sponge 
will be assessed post-procedure for signs of fracture 
or incomplete retrieval of the sponge. Subjects will 
undergo administration of the CytospongeTM 
according to the IFU.  Briefly, subjects will be placed in 
the seated position and will swallow the capsule with 
150 – 250 mL of water.  Additional water may be used 
if necessary. The sponge is attached to a length of 
suture material which passes out through the capsule. 
The suture is affixed to a retainer card which is held 
by the subject or administrator to prevent inadvertent 
swallowing of the suture.  The string is to be held 
without tension as peristalsis and gravity advance the 
capsule into the stomach.  
The capsule dissolves in the stomach, allowing the sponge to expand to its full size. Seven minutes and 
30 seconds to ten minutes after ingestion, the sponge is then withdrawn by gentle traction on the 
suture, collecting cells from the lining of the esophagus in passing.  
After retrieval, the string is cut and the retrieved foam sphere containing the cytological specimen is 
immersed in fixative and stored refrigerated (1° to 12°C [34° to 54°F]) until shipped.  Samples will be 
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shipped to an accredited pathology laboratory for processing. 
 
 
 
 
  
In the unlikely case of incomplete retrieval or sponge detachment, the sponge will be retrieved with a 
Roth net at the standard of care endoscopy which will routinely immediately follow the administration 
of the sponge per the study protocol. Any bleeding noted, either clinically following the sponge 
administration or due to blood on the sponge itself, will be similarly investigated, and, as necessary, 
treated during the subsequent endoscopy. Because study inclusion/exclusion criteria are designed to 
exclude those at highest risk for a bleeding complication, the risk of bleeding in this study should be 
extremely low. 
If a subject fails to swallow the Cytosponge, the subject will be asked to swallow again. Subjects who are 
willing to try again will be asked to wait 5 minutes before the Cytosponge is presented to them again. 
Subjects will be able to try up to two times before they are classified as “Cytosponge swallowing failure” 
and discontinued by the investigator. 
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The product is manufactured at a Medtronic facility located in Sunnyvale, California. 
 3DFNDJLQJ
The subject device the Cytosponge™ Cell Collection Device is a sterile single-use device. The 
Cytosponge™ Cell Collection Device consists of a clear, size 00 vegetable-material-derived capsule, 
which holds a 30mm spherical sponge inside of the capsule. The capsule containing the sponge is 
attached to silicone-coated braided polyester suture. The suture is attached and secured to a retainer 
card via an ABS plug. These materials are packaged inside a foil and polyethylene pouch. The product 
label is applied to the pouch and provides text containing the manufacturing lot and expiration date.  
 ,QWHQGHG3RSXODWLRQ
The intended population consists of people who are having an endoscopic exam to examine their 
esophagus, stomach, and first part of the small bowel and because the subject has suffered from GERD 
symptoms at least on a monthly basis for at least 6 months or patients who have been diagnosed with 
Barrett’s esophagus.  

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N/A 
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Refer to CytoKit IFU_717-0075-01(A) for product use information. 
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Each Investigator participating in the clinical trial and the associated clinical study staff will receive 
training on the clinical protocol, as well as hands-on training in the use of CytospongeTM Cell Collection 
Device and training on Visual Analog Scale.  The CASE II Clinical Study Training Plan describes in detail 
study training requirements. 
Sites are required to receive standardized training on Cytosponge administration before enrolling their 
first study subject. This will require recruiting and enrolling a cohort of healthy volunteers for training 
purposes. Participants enrolled for training purposes will not count toward enrollment on the study but 
should be approved by the site’s IRBs.  Prior to the recruitment of healthy volunteers, sites must receive 
explicit permission from the sponsor.  See Appendix III:  Sample Healthy Volunteer ICF.   
 3URGXFW5HFHLSWDQG7UDFNLQJ
Product information will be recorded in the packing slip, Kit Receiving and Disposition Log, and Device 
Accountability Log. These documents will be kept at the site and a copy will be sent to the sponsor to 
save in Trial Master Files. 
The packing slip will contain the kit and capsule lot numbers, kit and capsule expiration dates, date of 
order, and date of receipt. The site will confirm sponsor to confirm receipt of the product. 
 3URGXFW6WRUDJH
The device will be labeled CytoKit-R (Research Use Only) and should be stored in a secure (locked) area 
under the appropriate storage conditions. Access should be limited to designated study staff only. Refer 
to CytoKit IFU_717-0075-01(A) for appropriate storage condition information. 
 3URGXFW5HWXUQ
For all product returns not pertaining to a complaint, a Return Form is to be completed and the product 
is to be returned to the sponsor. For products being returned due to a complaint, Post-Market Vigilance 

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will provide a complaint number that will be included in the Return Form and shipping label.  Expired 
products can either disposed of or returned to the study sponsor.  
 3URGXFW$FFRXQWDELOLW\
The Kit Receiving and Disposition Log includes all information within the packing slip, as well as device 
condition, subject number, and the date the device was used. A copy of this log will be sent to the 
sponsor after every monitoring visit.  
A Device Accountability Log will be sent to the sponsor after a device is used or after the next 
monitoring visit. It will include the date of the procedure, the device and capsule lot numbers, and the 
subject number. 
 
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The study population includes patients with: 
x
Previous confirmed diagnosis of BE with intestinal metaplasia 
x
Self-reported heartburn or regurgitation on at least a monthly basis for at least 6 months (GERD 
arm) 
x
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) (refer to section 9.3) 
 6XEMHFW(QUROOPHQW
Potential subjects will be identified during their GI clinic or procedure visits at their treating institutions.  
All subjects will be screened and enrolled using ethics committee (EC) / Institutional Review Board (IRB)-
approved and HIPAA compliant methods.  
An investigator, study coordinator, or other qualified personnel will obtain consent prior to any study 
procedures.  Potential subjects will have an opportunity to carefully review the consent form.  The 
details of the study will be reviewed verbally, and all questions will be answered to the satisfaction of 
the patient.  Only adults with the ability to consent will be eligible for enrollment in this study.  After the 
subject signs the consent, a copy of the signed consent will be provided to the subject.  Once written 
consent has been obtained, the coordinator will collect demographic and historical information from the 
subject pertaining to history of BE and GERD. 

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The consent process will be documented by the coordinator in the subject’s study file. 
 ,QFOXVLRQ&ULWHULD
1) Male or female subjects, age 18 and above. 
2) Able to read, comprehend, and complete the consent form. 
3) Clinically fit for an endoscopy. 
4) One of the following options: 
b) 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 
c) 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 
d) Self-reported heartburn or regurgitation on at least a monthly basis for at least 6 
months (GERD arm). 
 
 ([FOXVLRQ&ULWHULD
1) Individuals with a diagnosis of an oropharynx, esophageal, or gastro-esophageal tumor, or 
ongoing symptoms of dysphagia. 
2) Any history of esophageal varices, or active stricture. 
3) 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 relevant guidelines 
such as those provided by the ASGE.   
4) Known bleeding disorder. 
5) Individuals who have had a myocardial infarction or any cardiac event < 6 months prior to 
enrollment. 
6) Individuals who have had a cerebrovascular event < 6 months prior to enrollment in which 
swallowing was affected. 
 3ULRUDEODWLYHRUUHVHFWLRQWKHUDS\RIWKHHVRSKDJXVLQFOXGLQJUDGLRIUHTXHQF\DEODWLRQ5)$
SKRWRG\QDPLFWKHUDS\3'7VSUD\FU\RWKHUDS\HQGRVFRSLFPXFRVDOUHVHFWLRQDQGRWKHU
DEODWLRQWKHUDSLHV
8) Any history of esophageal surgery, except for uncomplicated fundoplication. 
9) Do not need upper endoscopy as part of patient management. 

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10)Pregnancy 
 
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Assessment 
Screening/Enrollment 
Visit 
Follow-Up 
Phone Call  
(7 days +/- 3 
days after 
Enrollment)
Repeat 
Cytosponge  
Informed Consent Form   
X 
 
Demographics 
X 
 
Medical History  
X 
 
Inclusion/Exclusion Criteria  
X 
 
Cytosponge Administration 
X 
 
X1 
Visual Analog Scale 
X2 
 
Routine Care Endoscopy with 
Biopsy  
X3,4 
 
Impact of Event Scale 
 
X 
Procedure Preference and 
Acceptability Questionnaire 
 
X 
Adverse Events5 
X 
X 
X
1If the initial Cytosponge sample is inadequate, sites will be notified and subjects will be asked to return 
for repeat Cytosponge administration. Only the Cytosponge administration will be repeated.  
Questionnaires and the endoscopy procedure will not be repeated on these patients. 
2VAS should be administered immediately following completion of the Cytosponge and prior to the 
upper endoscopy. 

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3Routine care biopsies should be taken during the endoscopy following the Cytosponge as this is 
considered standard of care for the target population.  
4For subjects presenting for GERD, a single set of 4 quadrant biopsies (4 pieces of tissue total) of the 
gastric cardia (TGF+1) should be taken for this research study. The research specific biopsies will be 
taken in addition to any routine care biopsies taken during the procedure and will still be obtained even 
if routine care biopsies are not taken.  The Sponsor will pay for any charges related to collection and 
pathology of the research specific gastric cardia biopsies. 
It is encouraged for Investigators to take photos of the gastroesophageal junction (GEJ) during the 
endoscopy procedure.  
5Every adverse event must be reported to the sponsor and recorded in the electronic case report form. 
Sites are responsible for following local IRB guidelines for reporting adverse events to their local IRB. 
 6XEMHFW6FUHHQLQJ
During screening/enrollment, eligibility is assessed and those eligible and interested in participating are 
consented on the study. Once consent is obtained, subjects will undergo administration of the 
Cytosponge, complete a questionnaire, and proceed with routine care upper endoscopy immediately 
following completion of the Cytosponge in which biopsies are taken for clinical purposes and sent to 
pathology. 
The following will be completed during the screening/enrollment visit: 
x
Eligibility review 
x
Informed consent 
x
Cytosponge administration 
x
Visual Analog Scale 
x
Routine care upper endoscopy with biopsy 
x
Adverse event assessment 
x
Enrollment case report form (CRF): This captures demographics including race, ethnicity, 
gender, and year of birth, relevant BE and GERD medical history including 
documentation of endoscopic procedures received to date as well as pathology findings 
and endoscopic history related to current diagnosis.  
 
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Immediately following administration of the initial Cytosponge and retrieval, subjects will be 
administered a Visual Analog Scale (VAS). The VAS will not be administered during the repeat 
Cytosponge for subjects requiring a repeat Cytosponge. 

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If a patient is screened eligible and interested in the study, the patient will be consented on the study 
prior to any study procedure. Written informed consent will be obtained by qualified study personnel.  
Documentation of the consent process will be maintained in the subject’s research record. 
Patients will be given ample time to review the consent document and ask any questions they may have.  
A copy of the written consent form will be provided to the subject and the original maintained in the 
subject’s research record.   
If patients meet all inclusion and none of the exclusion criteria and consent to the study, they will be 
enrolled in the study. Subjects will be assigned a unique subject code.  
 &\WRVSRQJH$EUDVLRQ6FDOH
Cytosponge abrasions will be carefully assessed during the endoscopy and graded using a standardized 
abrasion scale (see Appendix I:  Cytosponge Abrasion Scale).  Physicians performing the endoscopy will 
be trained on use of the scale.    
 $GYHUVH(YHQW$VVHVVPHQW
Subjects should be assessed for any adverse events occurring before, during, or after Cytosponge 
administration. All adverse events occurring during the research study must be reported to the sponsor. 
Sites are responsible for following local IRB guidelines for reporting adverse events to their local IRB. 
 3ULRUDQG&RQFRPLWDQW0HGLFDWLRQV
Current use of anti-thrombotics (anti-coagulants and anti-platelet drugs) including but not limited to 
warfarin, clopidogrel, heparin and/or low molecular weight heparinmay be discontinued as per 
discretion of the principal investigator.  Reference Exclusion criteria #3.  
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FKDQJHVLQWKHLUPHGLFDOFRQGLWLRQV6XEMHFWVZLOOEHDEOHWRFRQWDFWWKHLQYHVWLJDWRUDWDQ\WLPH
GXULQJWKHVWXG\LIWKH\QRWHDQ\FKDQJHLQWKHLUPHGLFDOFRQGLWLRQ
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VKRXOGEHUHFRUGHGDVDQDGYHUVHHYHQWLIWKHIUHTXHQF\LQWHQVLW\RUWKHFKDUDFWHURIWKH
FRQGLWLRQZRUVHQVGXULQJWKHVWXG\SHULRG
*HQHUDO3K\VLFDO([DPLQDWLRQ)LQGLQJV
$WVFUHHQLQJDQ\FOLQLFDOO\VLJQLILFDQWDEQRUPDOLW\VKRXOGEHUHFRUGHGDVDSUHH[LVWLQJFRQGLWLRQ
$WWKHHQGRIWKHVWXG\DQ\QHZFOLQLFDOO\VLJQLILFDQWILQGLQJVDEQRUPDOLWLHVWKDWPHHWWKH
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 5HFRUGLQJ'DWD
Source data is all information, original records of clinical findings, observations, or other activities in a 
clinical trial necessary for the reconstruction and evaluation of the trial. Source data are contained in 
source documents. Examples of these original documents, and data records include: hospital records, 
clinical and office charts, laboratory notes, memoranda, subjects’ diaries or evaluation checklists, 
pharmacy dispensing records, recorded data from automated instruments, copies or transcriptions 
certified after verification as being accurate and complete, microfiches, photographic negatives, 
microfilm or magnetic media, x-rays, subject files, and records kept at the pharmacy, at the laboratories, 
and at medico-technical departments involved in the clinical trial. 
This study will utilize electronic case report forms (eCRFs). The study eCRF is the primary data collection 
instrument for the study. All data requested on the eCRF must be recorded. All missing data must be 
explained.  If a space on the eCRF is left blank because the procedure was not done or the question was 
not asked, this should be documented in the comments field.   
Along with the data collected during screening/enrollment, a follow-up phone call will be made and the 
following data will be collected: 
x
Impact of Event Scale 
x
Procedure Preference and Acceptability Questionnaire 
x
Adverse event assessment 
x
Follow-up electronic case report form (eCRF): This captures relevant information for 
questionnaire completion and assessment of adverse events. 
,PSDFWRI(YHQW6FDOH
The impact of event scale will be completed with the subject during the follow-up phone call and 
measures subjective distress related to administration of the Cytosponge. See $SSHQGL[,,
,PSDFWRI(YHQW6FDOH. 

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The procedure preference and acceptability questionnaire will be completed with the subject during the 
follow-up phone call.  This assessment collects subject preference for the Cytosponge or traditional 
upper endoscopy as well as willingness to undergo the procedure again. 
)ROORZXS3KRQH&DOO$GYHUVH(YHQW$VVHVVPHQW
During the follow-up phone call, subjects should be assessed for any adverse events that have occurred 
since administration of the Cytosponge. Only those events potentially related to participation in this 
research study must be reported to the sponsor. Sites are responsible for following local IRB guidelines 
for reporting adverse events to their local IRB. 
 
 'HYLDWLRQ+DQGOLQJ
The investigator must notify Medtronic and the reviewing IRB of any deviation from the protocol when 
specific to the protection of the life or physical well-being of a subject in an emergency. Such notice 
must be given as soon as possible, but in no event later than 5 working days after the emergency has 
occurred. Except in such an emergency, prior written approval by Medtronic is required for changes in 
or deviations from the plan. If these changes or deviations affect the scientific soundness of the plan or 
the rights, safety, or welfare of human subjects the IRB will also be notified. All other deviations will be 
reported per the site’s IRB deviation policy. Should any deviations from the protocol occur, these will be 
reviewed by Medtronic for their clinical significance. 
Protocol deviations identified by the Monitor during a monitoring visit should be discussed with the 
Principal Investigator/ Study staff involved at the time of discovery. Protocol non-compliance will be 
documented accordingly and communicated again in writing to the site within the follow-up letter. 
Monitors will also escalate the deviations significant in nature to the study manager (or designee), as 
soon as possible. 
 
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Subjects will be considered to have completed the study after completion of the last study visit (follow-
up phone call).  Subjects may be withdrawn prior to this for any of the following reasons: 
x
Death, or 
x
Lost to follow-up, or 
x
Withdrawal of consent, or 
x
Discontinuation by the investigator. 

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Documentation must be maintained at the site for any subject withdrawals.  Subjects unable to 
complete Cytosponge administration will be withdrawn from the study (discontinued by investigator). 
Three attempts at contact using two different methods are required prior to determining the subject is 
lost to follow-up. Attempts at contact must be with certified letters OR documented telephone contact. 
If a subject is withdrawn prior to completion of the study, the site should complete the Study Exit e-CRF. 
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LQFRPSHWHQW7KHVHHOHPHQWVIXUWKHUUHGXFHWKHRYHUDOOULVNIRUVHULRXVDGYHUVHHYHQWV
$OO VHULRXV DGYHUVH HYHQWV ZKLFK EDVHG RQ WKH LQYHVWLJDWRU¶V MXGJPHQW DUH FRQVLGHUHG WR EH GHYLFH
UHODWHG VKRXOG EH UHSRUWHG WR 0HGWURQLF*, 6ROXWLRQV ZLWKLQ  KRXUV DIWHU WKH LQYHVWLJDWRU LV PDGH
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The study may allow Medtronic and the study doctors to assess whether this procedure can be an 
acceptable method of collecting a sample of cells from the lining of the esophagus. 
This study will help in gathering information on the outcomes associated with the Cytosponge ™ 
Cell Collection Device and therefore might inform future decisions regarding this product and its 
indicated uses. 

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Risk analysis for Cytosponge™ Cell Collection Device was conducted in compliance with ISO14971. The 
overall evaluation of the residual system risks found no unacceptable hazards of significant impact to 
the safety and reliability of the Cytosponge™ Cell Collection Device. The residual risks of the 
Cytosponge™ Cell Collection Device, design, and process hazards were rated as BAR (Broadly 
Acceptable Region) or ALAP (As Low as Possible) in accordance with the risk acceptability criteria as 
documented in Risk Management Report
. 
x
Based on the risk analyses per the SHA 
, the dFMEA 
, and the pFMEA 
, we conclude that the current risk controls with respect to design and processes 
of the sterile Cytosponge™ Cell Collection Device (CYTO-101) have been reduced to acceptable level. 
x
Risks related to Secondary Intervention, Mucosal Laceration, Pre-Procedural Delay, Intra- 
Procedural Delay, Airway Obstruction, Unable to use sample for diagnosis, Infection, Minor 
Bleeding, Reaction due to non-Biocompatibility, Aspiration, Intestinal Obstruction and 
Dysphagia have been reduced to an acceptable level in BAR and/or ALAP-B risk regions for 
the Cytosponge™ Cell Collection Device (CYTO-101). 
x
Future updates to design and/or process pertaining to these risks will be captured with the 
inclusion of updated risk controls as applicable. 
x
None of the risks fall in the intolerable region and the current risks are reduced and/or 
continually controlled via existing measures; the residual risks from current risks are 
deemed acceptable based on the implementation of existing risk controls. 
x
This report is applicable only to sterile and non-sterile Cytosponge™ Cell Collection Device 
(CYTO-101) samples for intended use; performance/functionality testing was performed on 
e-beam sterilized samples since sterilization presents worst case processing/conditions as 
mentioned in
 performance testing for equivalency of non-sterile 
samples with sterile samples. 
x
Within this clinical trial, the benefits of using the Cytosponge™ Cell Collection Device (CYTO-101) 
for the intended use outweigh the risks. 
 
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It is the responsibility of the sponsor to notify all participating investigators of any adverse event 
associated with the study that is serious or unexpected.   
Every adverse event should be recorded in the electronic case report form. Any safety or device 
deficiency issues which may occur during training with healthy volunteers shall be reported using the   
Field and Technical report (FTR, form-0021). 
The following data must be documented: 
x
Type of event 
x
Subject number 
x
Time of occurrence: date, time 
x
Time of resolution: date, time 
x
Severity degree: mild / moderate / severe /  
x
Relationship to study device: no relationship/possible/probable/definite/unknown  
x
Measures taken 
x
Outcome of event: unchanged / worsened / improved / resolved / unknown / death 

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If timely completion of the electronic CRF is not possible, a paper copy can be completed and sent via 
fax or email GI Solutions at Medtronic (408) 328-7338 or FOLQLFDO#FRYLGLHQFRP.  If for any reason the 
form cannot be completed within 24 hours, a phone call should be made to the sponsor to meet the 
reporting timeline.  In the case of a telephone or faxed/emailed report, sites must still complete the 
electronic reportable event eCRF at the earliest possible opportunity, and no later than 72 hours 
following learning of the event.  
All other reportable events should be reported within 15 days of learning of the event.  Any safety or 
device deficiency issues which may occur during training with healthy volunteers shall be reported using 
the Field and Technical report (FTR, form-0021). 
 
 'DWD5HYLHZ&RPPLWWHHV
Data Monitoring Committee (DMC) or Clinical Events Committee (CEC) will not be used for this study. 
 6WDWLVWLFDO'HVLJQDQG0HWKRGV
For the primary objectives, to assess the acceptability of the Cytosponge in subjects with BE, we will 
assess the distribution of Impact of Event Scale scores, and the intrusiveness and avoidance subscales. 
We will generate measures of central tendency and distribution of these data. Bivariate analysis will be 
performed to assess for predictors of low tolerance of Cytosponge surveillance, and a logistic regression 
model created to assess these factors while controlling for potential confounders. Data will be 
compared to population norms in published literature1 using parametric statistics. VAS scores will be 
calculated, and measures of central tendency and distribution reported. 
 
Subjects’ preferences for Cytosponge versus endoscopic surveillance, as well as willingness to undergo 
the procedure again, will be measured as proportions, with bivariate and multivariate analyses for 
predictors of preference performed. 
 
For the second primary objective, to assess the adequacy of samples, sample adequacy will be treated 
as a dichotomous variable.  For purposes of this investigation, an adequate sample will be one in which 
at least one columnar cell is present.  Sample adequacy will be presented as a proportion of subjects 
who fulfill this definition after up to two total administrations of the Cytosponge, as noted in the 
methods. 
 
For the first three secondary objectives, to assess the operating characteristics of Cytosponge against 
various gold standards, initially 2x2 tables will be constructed demonstrating Cytosponge and the gold 

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standard findings (Y/N for BE via endoscopy and Y/N for Intestinal Metaplasia (IM) via biopsies). Both 
endoscopic evidence of BE and pathological confirmation of specialized IM (intestinal metaplasia with 
goblet cells) will be used in the final diagnosis of BE. Sensitivity, specificity, positive predictive value, 
negative predictive value and accuracy will be calculated. Because Cytosponge positivity may vary based 
on the burden of BE, we will perform sensitivity analyses, defining “positive” cases as those with BE of 
шϮĐŵŝŶůĞŶŐƚŚ͕ĂŶĚƚŚĞŶшϯĐŵŝŶůĞŶŐƚŚ͕ƚŽĂƐƐĞƐƐŝmpact of disease burden on operating 
characteristics. Multivariate models controlling for age, sex, burden of disease, and other potential 
confounders will be constructed, to assess the impact of these factors on test accuracy. Although we do 
not expect to see an association between the degree of dysplasia and Cytosponge positivity, exploratory 
analyses will be performed using degree of dysplasia as a predictor variable, and Cytosponge positivity 
as the outcome variable. For the fourth secondary objective, to assess the degree of mucosal abrasion 
following Cytosponge, endoscopic abrasion scores will be correlated with the presence of columnar cells 
on the H&E slide made from the Cytosponge samples. 
 
While the operating characteristics of Cytosponge in our patient population are unknown, the numbers 
for this post-market study were selected for several reasons.  Approximately 50% of the patient 
population at the involved tertiary care centers have dysplastic BE (25% low-grade dysplasia, 25% high-
grade dysplasia), so assessment of 275 patients (with an enrollment ratio of at least >50% BE and >25% 
GERD) should allow an adequate number of subjects with dysplastic disease to assess performance 
characteristics with reasonable accuracy. Ten percent of patients with chronic GERD symptoms can be 
expected to harbor BE, leaving us 75 patients with which to assess specificity, as well as to assess 
acceptability in patients without disease.  For the safety perspective, a sample size of 50 will have 
greater than 90% probability of detecting a rare event that occurs at a rate of 5%. Results of this study 
will be used to provide more accurate parameters for power of subsequent studies. 
All individuals offered the Cytosponge will be included in analyses of acceptability and adequacy of 
sampling. All individuals with adequate Cytosponge samples and endoscopy (within 48 hours of 
Cytosponge) will be included to determine the sensitivity for diagnosis of BE from the TFF3 data (95% 
confidence intervals will be used). 
 
In an effort to understand the sensitivity and specificity of the test, an interim analysis of the data, 
based on the statistical methodology outlined above, may be performed after approximately half the 
study subjects have primary outcomes. 
 
To assess safety (fifth secondary objective), the number and percentage of subjects with adverse events 
related to Cytosponge administration will be summarized by MedDRA system organ class and preferred 
term overall, and by severity. 

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This clinical investigation will be conducted in accordance with the US and international standards of 
Good Clinical Practice (FDA Title 21 and International Conference on Harmonization guidelines), 
applicable government regulations, Institutional research policies and procedures, ethical principles that 
have their origin in the Declaration of Helsinki, ICH-GCP, and any regional or national regulations, as 
appropriate.  
 
The clinical investigation will not begin until all necessary approvals/favorable opinions are obtained 
from the appropriate IRBs or regulatory authority, as appropriate. Should an IRB or regulatory authority 
impose any additional requirements, they will be followed. Information regarding the study and study 
data will be made available via publication on clintrials.gov. Additionally, the results of this study will be 
submitted for publication in an appropriate journal. 
 
This protocol and any amendments will be submitted to a properly constituted independent IRB, in 
agreement with local legal prescriptions, for formal approval of the study conduct. The decision of the 
IRB concerning the conduct of the study will be made in writing to the investigator and a copy of this 
decision will be provided to the sponsor before commencement of this study. The investigator should 
provide a list of IRB members and their affiliate to the sponsor. 
 
All subjects for this study will be provided a consent form describing this study and that provides 
sufficient information for subjects to make an informed decision about their participation in this study. 
Sample consent forms will be provided by the lead site. These consent forms include a consent for the 
study as well as a consent for storage of samples for future use. All consent forms will be submitted with 
the protocol for review and approval by the IRB for the study. The formal consent of a subject, using the 
IRB-approved consent form, must be obtained before that subject undergoes any study procedure. The 
consent forms must be signed by the subject or legally acceptable surrogate, and the investigator-
designated research professional obtaining the consent.  
 

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The investigator will permit study-related monitoring, audits, and inspections by the IRB, the sponsor, 
the lead site, government regulatory bodies, and University compliance and quality assurance groups of 
all study related documents (e.g. source documents, regulatory documents, data collection instruments, 
study data etc.). The investigator will ensure the capability for inspections of applicable study-related 
facilities (e.g. pharmacy, diagnostic laboratory, etc.). Participation as an investigator in this study implies 
acceptance of potential inspection by government regulatory authorities and applicable University 
compliance and quality assurance offices. 
Participation as an investigator in this study implies acceptance of potential inspection by government 
regulatory authorities and applicable University compliance and quality assurance offices. 
It is the responsibility of the Principal Investigator to oversee the safety of the study at his/her site.  This 
safety monitoring will include careful assessment and appropriate reporting of adverse events as noted 
above, as well as the construction and implementation of a site data and safety-monitoring plan, if 
required. Medical monitoring will include a regular assessment of the number and type of serious 
adverse events.  
 'DWD0DQDJHPHQW
This study will utilize an electronic database and eCRF or paper CRFs.  All data requested on the eCRF are 
considered required.  Data points not collected and/or recorded will be considered deviations unless 
otherwise specified.  The Principal Investigator must ensure the accuracy and completeness of the 
recorded data and then provide his/her electronic signature on the appropriate eCRFs.  The 
Investigator’s electronic signature for specific eCRFs will be documented in compliance with local 
regulations.  Changes to data previously submitted to the sponsor will require a new electronic signature 
by the Investigator to acknowledge/approve the changes. 
 
Visual and/or computer data review will be performed to identify possible data discrepancies.  Manual 
and/or automatic queries will be created in the Oracle remote data capture (RDC) system and will be 
issued to the site for appropriate response.  The site staff will be responsible for resolving all queries in 
the database. 
 
The investigator must agree to the inspection of study-related records by the Regulatory 
Authority/Sponsor representatives, and must allow direct access to source documents to the Regulatory 
Authority/Sponsor representatives. 

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The investigator must agree to the inspection of study-related records by the Regulatory 
Authority/Sponsor representatives, and must allow direct access to source documents to the Regulatory 
Authority/Sponsor representatives 
 &RQILGHQWLDOLW\
Information about study subjects will be kept confidential and managed according to the requirements 
of the Health Insurance Portability and Accountability Act of 1996 (HIPAA). Those regulations require a 
signed subject authorization informing the subject of the following:  
x What protected health information (PHI) will be collected from subjects in this study 
x Who will have access to that information and why 
x Who will use or disclose that information 
x The rights of a research subject to revoke their authorization for use of their PHI.  
 
In the event that a subject revokes authorization to collect or use PHI, the investigator, by regulation, 
retains the ability to use all information collected prior to the revocation of subject authorization. For 
subjects that have revoked authorization to collect or use PHI, attempts should be made to obtain 
permission to collect at least vital status (i.e. the subject is alive) at the end of their scheduled study 
period. 
 /LDELOLW\
Medtronic maintains appropriate clinical study liability insurance coverage as required under applicable 
laws and regulations and will comply with applicable local law and custom concerning specific insurance 
coverage.  If required, a clinical study insurance statement/certificate will be provided to the IRB. 
 &,3$PHQGPHQWV
No changes to the protocol will be permitted without the written approval from Medtronic and the 
IRB/EC (at the discretion of the PI and the IRB). It is the responsibility of the sponsor to notify all 
participating investigators of any revisions to the protocol. 

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The investigator will maintain the records of the study including all pertinent correspondence, the study 
protocol with any/all amendments, all correspondence with and approval from the IRB/EC, the clinical 
trial agreement, the Investigator Agreement, investigational device accountability records, individual 
subject records, and signed ICFs.  Subject files and other source data must be kept for a period of not 
less than 2 years after the latter of the following two dates:  the date on which this investigation is 
terminated or completed, or the date that the records are no longer required for purposes of supporting 
a premarket application.  Records may need to be maintained by the Principal Investigator for a longer 
duration if national regulations require or if agreed to in writing with the Sponsor.  All data and 
documents should be made available if requested by relevant authorities. 
 3XEOLFDWLRQDQG8VHRI,QIRUPDWLRQ
Neither the complete nor any part of the results of the study carried out under this protocol, nor any of 
the information provided by the sponsor for the purposes of performing the study, will be published or 
passed on to any third party without the consent of the lead investigator, Dr. Nicholas Shaheen. Any 
investigator involved with this study is obligated to provide the lead investigator with complete test 
results and all data derived from the study. The results from this study will not be used to influence 
patient management or follow-up.  
The Medtronic Publication and Authorship Policy is aligned with the International Committee of Medical 
Journal Editors (ICMJE) recommendations (www.icmje.org). Medtronic will seek to publish, in 
appropriate peer-reviewed journals and scientific conferences, results of clinical studies where human 
subjects are involved, regardless of outcome. While study results are owned by Medtronic, all data on 
which a publication is based will be made available to all authors as required for their participation in 
the publication process. Furthermore, data may be published or used by study investigators provided 
that such publication or use is in accordance with this this protocol, the Medtronic Publication and 
Authorship Policy, and the Clinical Investigation Agreement. Investigators must submit a copy of all 
manuscripts and/or abstracts to Medtronic for review and comment 30 days prior to planned 
submission. Medtronic acknowledges that its right to review and comment shall relate solely to the 
proprietary, licensing, and/or confidential rights Medtronic may have in such proposed publication, 
rather than whether such results and/or opinions are favorable to Medtronic.   
 
The publication of sub-studies, post-hoc analyses, regional results, or single-center experiences based on 
multicenter clinical studies should not precede that of the primary multicenter publication, and should 
cite the primary publication whenever possible, as required by specific journal and scientific meeting 
guidelines.  
 
Medtronic involvement in a publication (e.g., funding of the study; sponsor of the study; collection, 
analysis, and interpretation of data; professional writing assistance) must be disclosed according to 
journal-specific policies, submission requirements, and prevailing editorial standards, in addition to 

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those specified by the International Committee of Medical Journal Editors. Authors must ensure that an 
acknowledgement/disclosure statement is included in the body of the manuscript for Medtronic to 
reviewfor accuracy. All authors must also disclose financial or personal affiliations that could be 
considered conflicts of interest as per journal/conference requirements. 
 
To enable health care providers, payers, and patients access to the wealth of Medtronic’s research, 
Medtronic will report its scientific data in accordance with the principles outlined in the Guidance 
Document on Registration and Reporting Results of Company-Sponsored Clinical Trials Under FDAAA 
2007 (Title VIII). 
 6XVSHQVLRQRU(DUO\7HUPLQDWLRQ
The Sponsor reserves the right to suspend or discontinue the study at any stage, with suitable written 
notice to all investigators, all reviewing institutional review boards (IRBs) or ethic committees 
(ECs).  Similarly, investigators may withdraw from the study at any time, subject to providing written 
notification to the Sponsor 30 days prior to the date they intend to withdraw.  However, the Sponsor 
and investigators will be bound by their obligation to complete the follow-up of subjects already 
participating in the study.  The subjects must be followed according to the clinical protocol, and 
information obtained during subject follow-up shall be reported to the Sponsor on the appropriate 
eCRF. 
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Version Summary of Changes 
Author(s)/Title
A 
x
Initial version 
 
Director, 
Clinical Affairs 
B 
x
Added risks: There is the possibility of aspiration or airway 
obstruction whenever instrumentation of the esophagus or stomach 
is performed by access through the mouth.  In the setting of 
aspiration, infection is also a risk. Because the patient is not sedated 
and the device does not render the upper esophageal sphincter 
incompetent, these risks are expected to be minimal.  Additionally, 
although the sponge is soft, patients could experience abrasions or a 
laceration of any of the mucosal surfaces of the mouth, stomach or 
esophagus which come in contact with the sponge; this could result in 
bleeding from any of the aforementioned mucosal surfaces 
x
Updated exclusion criteria: Are unable to discontinue anti-
thrombotics including but not limited to warfarin, clopidogrel, 
heparin and/or low molecular weight heparin for 7 days prior and 7 
days after procedure. 
x
Added exclusion criteria: Pregnancy 
x
Revised Assessment of Safety Section 
 
Clinical 
Program 
Manager 
C
x
Revised Assessment of Safety Section: The relationship of adverse 
event to the study, serious adverse events, anticipated adverse event 
reactions associated with Cytosponge cell collection device. 
x
Revised protocol compliance and deviation reporting
Clinical 
Program 
Manager 
D 
x
Added general design: All biopsies are per routine care and are at the 
discretion of the physician performing the procedure. No biopsies will 
be taken specific to this study. Biopsies not taken at the physician’s 
discretion is not a protocol deviation. Endoscopy without biopsies 
taken will still count toward enrollment and their data will be used in 
the final data set. 
 
Clinical 
Program 
Manager 
E 
x
Cardia Biopsies: For subjects presenting for GERD, a single set of 4 
quadrant biopsies (4 pieces of tissue total) of the gastric cardia (TGF+3) 
will be collected during the endoscopy procedure.  All research-specific 
gastric cardia biopsies, as well as any routine care tissue biopsies will 
undergo standard processing and H&E staining at the home institution, 
with assessment by expert gastrointestinal pathologists.  The sponsor will 
pay for any charges related to collection and pathology of the research-
specific gastric cardia biopsies.   
x
Removed from 3.1 General Design: “Biopsies not taken at the physician’s 
 
Clinical 
Program 
Manager 

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discretion is not a protocol deviation.” 
x
Photos of the gastroesophageal junction (GEJ): It is encouraged for 
investigators to take photos of the GEJ during the endoscopy procedure. 
x
Interim Analysis: In an effort to understand the sensitivity and specificity 
of the test, an interim analysis of the data, based on the statistical 
methodology outlined above, may be performed after approximately half 
the study subjects have primary outcomes. 
x
Quality Assurance of Cytosponge Samples: For quality assurance, 
Cytosponge samples may be sent to the University of Cambridge to be 
processed and read, as needed to optimize training at the central lab.  
These results will be compared to those reported by Miraca.  
x
Update to 3.5 Protocol Map: Map updated to include collection of gastric 
cardia biopsy in subjects presenting for GERD.   
x
Adverse Event (AE) Reporting Clarification: Updated wording from, “Only 
those events potentially related to participation in this research study…” 
to “Every adverse event must be reported to the sponsor and recorded in 
the electronic case report form.  See section 7.2 for definition of a 
reportable adverse event and documentation guidance.”  Removed 
“theoretical” and added “and/or irritation of” to section 7.2.4 Anticipated 
adverse events reactions associated with Cytosponge™ Cell Collection 
Device 
x
Updated Revision to Rev. E and Revision date to 15.December.2015  
 
F 
x
Update to inclusion criteria 4a to include protocol amendment memo, “If 
the subject does not have documented Prague Classification prior to 
screening, and the PI is convinced that the subject will meet the inclusion 
criteria based on previous documentation, 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 
determined at the time of study endoscopy, the subject may still be 
enrolled but not included in the data analysis with this cohort. The data 
may be analyzed in a separate cohort. 
x
Added clarification to Safety Assessment noting all serious adverse events 
will be adjudicated.   
Updated risk section 11.1  
There are several possible risks that could occur when swallowing the 
Cytosponge capsule which include but are not limited to: 
 
x
Aspiration (accidentally inhaling material from the stomach into the 
lungs) and/or airway obstruction are possibilities but these risks are 
expected to be minimal. 
x
Although the sponge is soft, possible risks include, bleeding, pain, 
vomiting, sore/irritated throat, and burning sensation from any mucosal 
 
 
Director, 
Global Clinical 
Affairs 
 Sr. 
Clinical Project 
Specialist 
 
Clinical 
Research 
Associate 
 
 Sr. 
Clinical Project 
Specialist 
 

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Page 60 of 61 
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surfaces of the mouth, stomach or esophagus (swallowing tube) which 
comes in contact with the sponge. 
x
Laceration of any mucosal surface coming into contact with the 
sponge is possible, including mucosal surfaces of the stomach, 
esophagus, throat or mouth.  Although very unlikely, perforation of 
the stomach or esophagus is also possible which could require 
secondary intervention. 
x
Although the risk has been found to be 2%, sponge detachment from the 
suture could also occur. Should this occur, the sponge will be retrieved 
during the planned endoscopy that follows administration of the sponge. 
x
Although not observed in previous Cytosponge studies the risk of 
infection or intestinal obstruction is a possibility. 
The current study has been designed to minimize occurrence of these 
potential risks by use of the exclusion criteria.  Most subjects enrolled in 
this study will have previously received an upper endoscopy, which will 
document the absence of esophageal varices and strictures. During 
administration of the sponge, the patient is not sedated and the device 
does not render the upper esophageal sphincter incompetent. These 
elements further reduce the overall risk for serious adverse events 
x
BE arm biopsies are required during standard upper endoscopy  
x
Although the risk has been found to be 2%, sponge detachment from the 
suture could also occur. 
Updated Revision to Rev. F and Revision date to 23.Sept.2016  
G 
x
Investigation Purpose:  ADD GERD: 
To assess the utility of the Cytosponge device as a non-endoscopic 
method for collecting surface cells from the esophagus in patients with BE 
and GERD 
 
x
Primary Objective(s):  Remove “within the last 5 years”: 
To assess the acceptability of a novel, minimally invasive esophageal 
mucosal sampling technique, the Cytosponge 1) in subjects undergoing 
surveillance of BE who have had at least a C1 or M3 segment confirmed 
(or medically suspected), within the last 5 years, and 2) in subjects with 
GERD undergoing screening for BE.  
 
x
Sample Size:  Increase the sample size by 100 subjects:   120 275 subjects 
(Enrollment ratio of at least >50% BE and >25% GERD) 
 _with BE (at least C1 or M3 confirmed at Cytosponge endoscopy, and 75 
55 subjects with GERD symptoms undergoing screening for BE. 
 
x
Inclusion Criteria:  4)a)  Remove “in last 5 years”  
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 
 
 Sr. 
Clinical Project 
Specialist 
 
 
Clinical 
Research 
Specialist  

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(C1+ or CXM3+) (BE arm) in last 5 years. OR 
 
x
Updated Exclusion #3:  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 also 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 judgment and should 
consult relevant guidelines such as those provided by the ASGE.   
 
x
Repeat sponge procedure: Remove 30 days later (+/- 10 days). 
 
x
Subjects will be contacted via phone 7 Days Change 2 days to 3 days: (+/- 
2 3 days).   
x
Lab processing – remove time of lab processing:  Samples will be shipped 
to an accredited pathology laboratory for processing before the end of 
the next business day. 
 
x
Add Appendix III:  Healthy Volunteer ICF 
 
x
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GD\VDIWHU&\WRVSRQJHDGPLQLVWUDWLRQ. 
 
x
Subjects who undergo same day ablative therapy (as Cytosponge testing) 
will Impact of Event Scale scores evaluated separately as opposed to the 
BE surveillance group.   
 
x
Secondary Objectives 2)  Add: Patients who are undergoing ablative 
therapy on the day of Cytosponge testing must have biopsies within 2 
months prior to surgery.