Pilot Study for Imaging of the Esophagus Using a Tethered Capsule OCT Endomicroscopy in the Primary Care Setting
Phase: NA
Conditions: Healthy
Sponsor: Massachusetts General Hospital

STUDY PROTOCOL VERSION 
08/04/2017
Pilot study for imaging of the esophagus using a tethered capsule OCT 
endomicroscopy in the Primary Care setting. 
MGH Principal Investigator:  
Guillermo Tearney M.D. Ph.D. 

Wellman Center for Photomedicine 
MGH 
Pilot study for imaging of the esophagus using a tethered capsule OCT endomicroscopy in the 
Primary Care setting 
 
 
 
 
A. BACKGROUND AND SIGNIFICANCE 
 
Barrett ’s esophagus and esophageal adenocarcinoma  
Barrett’s esophagus (BE) is a condition associated with older age, Caucasian race, 
and longstanding gastroesophageal reflux disease (GERD),1 where the normal 
squamous epithelium is replaced by intestinal epithelium, also termed specialized 
intestinal metaplasia (SIM).2 BE can undergo dysplastic progression, leading to 
esophageal adenocarcinoma (EAC), a cancer with a poor overall 5-year survival of 
10%.3-5 There are approximately 8,000 new cases of EAC per year in the US6 and its 
incidence is growing at a higher rate than any other cancers, with a six-fold increase 
over the past three decades.1 
 
Current management of BE. Because patients with BE carry 35-120 times higher risk 
of developing EAC7,8 and treatment of early stage cancer can be curative, the American 
College of Gastroenterology (ACG),9 the American Gastroenterological Association 
(AGA),10 and the American Society for Gastrointestinal Endoscopy (ASGE)11 recommend 
that patients with risk factors for Barrett’s esophagus, such as chronic GERD, age over 
50, male sex, elevated body mass index, and hiatal hernias be screened for SIM with 
upper endoscopy (esophagogastroduodenoscopy - EGD). For this procedure, the 
patient is sedated and a video endoscope is inserted transorally into the insufflated 
esophagus. The gastroenterologist then inspects the esophagus, stomach, and 
gastroesophageal junction (GEJ). If abnormal, salmon- colored mucosa is identified 
proximal to the diaphragmatic pinch, a biopsy is excised and sent to pathology for 
analysis. Patients found to have histopathologic evidence of SIM undergo regular 
surveillance, which consists of taking random, 4-quadrant biopsies every 1-2 cm along 
the longitudinal extent of the BE segment.9,11 Surveillance intervals every 2-5 years are 
recommended in patients without dysplasia and every 6 months for patients with low-
grade dysplasia (LGD).9,11,12 For patients with high-grade dysplasia (HGD), either 
surveillance at 3 months intervals, ablation, endoscopic mucosal resection (EMR), or 
esophagectomy is recommended.9,11-13 
 
Limitations of endoscopic screening 
At present, approximately 1M patients in the US are screened with upper endoscopy 
for BE every year.14 At an average of $1000 per procedure, screening for BE amounts 
to $1B annual expense to our health care system. Any method to lower the cost of 
screening today would be of great benefit to society in this time of escalating health 
care costs 
 
Even though upper endoscopic screening is widely practiced, many patients with 
GERD are still not screened. This fact could partially explain why > 95% of patients 
who currently present with EAC have not had a prior diagnosis of BE.15 However, 
screening the entire GERD population at risk would not be economically feasible, as 
there are 40-60M patients with GERD in the US16 and an estimated 3-12M patients 
with BE.17,18  Moreover, recent studies have shown that 39-44% of patients with BE19  
and EAC20 did not report symptoms of GERD, indicating that the potential screening 
pool may be even larger. A recent medical decision analysis performed to assess the 
cost-effectiveness of endoscopic screening in patients with GERD concluded that the 
expense of endoscopy was one of the most important factors determining whether or not 
screening was cost-effective.21 This analysis also indicated that screening for SIM could 
be justified.21 
 
 

Wellman Center for Photomedicine 
MGH 
Pilot study for imaging of the esophagus using a tethered capsule OCT endomicroscopy in the 
Primary Care setting 
 
 
 
 
 
Besides cost, another limitation of upper endoscopy for screening is its low accuracy. 
Studies have shown that endoscopists correctly identify SIM in only approximately 40- 
50% of cases.22,23  Even when endoscopy does identify abnormal mucosa, the fractional 
area of tissue sampled by biopsy is low and SIM or dysplasia may be missed.24,25 A 
separate cost-effectiveness analysis by Inadomi et al. showed that screening and 
subsequent surveillance was cost effective only in those patients with dysplasia.26 This 
study suggests that the best screening method would be capable of identifying 
dysplastic SIM, something that is not possible with endoscopy. The diagnostic failings of 
upper endoscopy, combined with its high cost make it a good target for improvement. 
 
Finally, screening is only useful if there is a viable follow-up option that will change 
outcome for those patients who have a positive test. Random biopsy surveillance, the 
follow-up procedure for patients found to have SIM, is also subject to significant 
limitations. Since dysplasia and adenocarcinoma are not evident by endoscopy and 
are focally distributed, random biopsy is inherently prone to sampling errors. Even 
when using the largest biopsy forceps available (jumbo biopsy forceps), most biopsy 
procedures interrogate < 1% of the involved segment of BE.24,25 The inadequacy of 
random biopsy is highlighted by histopathologic analyses of esophagectomy specimens 
that have found undetected intramucosal carcinoma (IMC) in 40% and invasive 
adenocarcinoma in 13% of patients with a prior diagnosis of HGD only.27-29 A method 
for guiding the gastroenterologist to excise biopsies from regions that contain the most 
severe disease should improve the overall effectiveness of screening and surveillance of 
BE patients. 
 
 
Cost of sedation and upper endoscopy 
Sedation, via IV administration of sedatives and narcotic analgesics, is the single most 
important contributor to the high cost of upper endoscopy and is estimated to account 
for 30-50% of the total procedural cost.30 Because of the mortality and morbidity 
associated with complications related to sedation, patients must undergo continuous 
cardiopulmonary monitoring and nursing support during the endoscopic procedure. Post-
procedural recovery also contributes to the expense, as it requires additional nursing, 
monitoring, and patient care in a large and specialized physical space. After discharge, 
patients frequently need to be escorted home and lose at least a day of work.31 
 
Optical Coherence Tomography (OCT) 
Optical Coherence Tomography is a optical diagnostic technology that provides a high- 
resolution (10 µm axial resolution) cross-sectional images of tissues in noninvasive 
way.32,33 We have demonstrated that OCT has the potential to provide more diagnostic 
information a s  i t  can distinguish BE and dysplasia with accuracies ranging from 80-
90% and be less costly than upper endoscopy.34-36  
 
We have utilized the high-speed version of OCT to perform three-dimensional, 
architectural microscopy of long segments of luminal organs using helically scanning 
balloon- centering catheters.37-39 We have successfully conducted balloon-catheter 
esophageal OCT in over 100 patients40 and have shown that it is a safe and rapid 
procedure. With this technology, however, OCT balloon catheter placement requires 
sedated upper endoscopy. 

Wellman Center for Photomedicine 
MGH 
Pilot study for imaging of the esophagus using a tethered capsule OCT endomicroscopy in the 
Primary Care setting 
 
 
 
 
Tethered capsule OCT endomicroscopy 
We have developed a tethered capsule OCT device intended as an inexpensive 
screening tool for BE.41,42 The capsule, which is attached to a thin, flexible tether, 
is reusable after being processed by a standard disinfection technique. Used without 
sedation, the capsule is swallowed by the patient and travels in the esophagus to 
the GEJ via peristalsis. Cross-sectional microscopic OCT images of the entire 
esophagus are collected during transit. The total time needed for swallowing, 
imaging and retrieval does not exceed 10 minutes. We have tested the feasibility 
and the tolerability of this new OCT screening technology in 77 procedures in healthy 
volunteers and patients with various esophageal disease including BE. The 
procedure has been safe and well tolerated. High quality microscopic images of the 
esophagus have been obtained in 90% of the enrolled subjects. 
 
Tethered capsule OCT endomicroscopy for population based screening 
Our previous clinical experience with tethered capsule OCT endomicroscopy has been 
in the setting of gastroenterology endoscopy clinics. These study procedures were 
conducted in GI endoscopy suites by gastroenterologists and GI nurses. While these 
studies have been useful to determine the safety and feasibility of capsule 
endomicroscopy in human subjects, the ideal setting for screening patients for BE is in 
the primary care office. We therefore propose to conduct a study to evaluate the 
feasibility and acceptability of using of our tethered capsule endomicroscopy device in 
the primary care office setting. 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
  
 
 
 
 
 
B. SPECIFIC AIMS 
 
The goal of this research is to test the feasibility and acceptability of a tethered capsule 
OCT endomicroscopy as a device for population based screening in the primary care 
practice environment. 
 

Wellman Center for Photomedicine 
MGH 
Pilot study for imaging of the esophagus using a tethered capsule OCT endomicroscopy in the 
Primary Care setting 
 
 
 
 
 
 
C. SUBJECT SELECTION 
 
Sixty volunteer subjects scheduled for non-urgent visits to outpatient primary care 
practices at MGH will be enrolled in the study. 
 
Subjects will be selected according to the following inclusion and exclusion criteria: 
 
THE INCLUSION CRITERIA: 
 
- Patients must be scheduled for non-urgent appointment at primary care practice 
including annual wellness visits and routine follow-up appointments. 
- Patients must be over the age of 18 
- Patient must be able to give informed consent 
- Patient must have no solid food for 4 hours prior to the procedure, and only clear 
liquids for 2 hours prior to the procedure. 
 
 
THE EXCLUSION CRITERIA: 
- Subjects with current symptoms of dysphagia 
- Subjects with any history of intestinal strictures, prior GI surgery, or history of 
intestinal Crohn’s disease. 
- Subjects with current symptoms of fever, nausea or sore throat at the time of the 
appointment. 
- Pregnancy 
 
RECRUITMENT METHODS 
 
Potential participants will be identified from the primary care physician’s schedule by 
reviewing the electronic clinic schedule at least 2 weeks in advance of the visit. On a 
regular basis, a list of potentially eligible subjects (based on reason for visit and age) will 
be sent to the primary care physician via Partners email to seek permission to contact 
each patient about the study. After the primary care physician has given permission, a 
letter cosigned by the primary care physician and the PI will be sent to the potential 
participants as well as a copy of a consent form and a short fact sheet about the study 
(included). Contact details will be provided in the letter for all potential subjects to call 
with questions or concerns regarding the research study, or to opt out in advance of the 
scheduled visit if they choose to do so. Subsequently, potential participants will be 
contacted by telephone about 3 days prior to the scheduled visit to assess if they would 
be interested in participating, remind them not to eat for at least 4 hours prior to the visit 
and answer any questions they might have.  
 
On the day of the visit, potential participants will be approached by the study staff 
member. The details of the study will be reviewed and the questions from the 
participants about the study will be answered. The capsule operator is a designated 
study member trained in operating the capsule. The PCP will also be available to 
answer any questions about the study. The consent for this study will be obtained by a 
licensed physician or designated research study member. This will happen either 

Wellman Center for Photomedicine 
MGH 
Pilot study for imaging of the esophagus using a tethered capsule OCT endomicroscopy in the 
Primary Care setting 
 
 
 
 
immediately before or after the clinic visit. Participants can change their mind at any 
time and withdraw from the study at any point, including after signing the consent form 
 
D. STUDY PROCEDURES 
 
 
 
 
  
 
  
 
 
 
  
 
 
 
PROCEDURE 
The procedure will take place immediately before or after the patients’ Primary Care 
appointment in an available exam room within the primary care practice suite. As 
described above, patients will have received written information prior to the day of the 
capsule procedure and patients will have another chance to discuss the procedure with 
the study coordinator and clinical study staff during the consent process prior to the 
capsule procedure. Participation in this study is completely voluntary, and the patient can 
stop the procedure at any time.  
 
According to the sterilization method in place at the MGH GI unit, the capsule and sheath 
will undergo a high level disinfection before each use. This protocol is identical to that of 
MGH GI unit endoscopes and esophageal manometry study catheters (ESMO), both of 
which are passed through the upper GI tract and removed. Alternatively, before each 
case, the capsule and sheath will be sterilized at the MGH Sterile Department using cold 
gas Ethylene Oxide. 
 
For each of the consenting patients, inclusion criteria and clinical characteristics such as 
age, sex, body mass index (BMI), current medication regimen and GI related history will 
be recorded. Study subjects will be asked to verify that they have not consumed solid 
foods in the past 4 hours, and have had only clear liquids for the past 2 hours. Women of 
child-bearing age will be asked to take a urine pregnancy test and women with positive 
test results will be excluded from the study. 
 
Subjects will be seated and wearing their own clothing for the procedure. They do not 
need to change into the hospital gown. Subjects will be asked to sip water from a straw 
to facilitate swallowing the capsule. Subjects will be given the option of using an over the 
counter throat numbing spray
, which will reduce the 
irritation to the back of the throat by the tether. Subjects typically will use the spray few 
minutes before the start of the procedure. Subjects will also be given the option to use 
 a readily available over the counter water-based lubricating 
spray that helps the subject swallow the capsule more easily. Subjects typically use 2-4 
sprays (.3-.6 ml) 
 before the procedure. We recognize that everyone utilizes 
different strategies to swallow capsules and we would like to provide them with whatever 

Wellman Center for Photomedicine 
MGH 
Pilot study for imaging of the esophagus using a tethered capsule OCT endomicroscopy in the 
Primary Care setting 
 
 
 
 
they need to successfully swallow. This may include using food products such as 
applesauce, pudding, and yogurt as well as implementing additional swallowing 
methods. The texture and density of the food products can make it easier to swallow 
capsules whole. These methods are optional and entirely up to the subject. Should the 
study subject not be able to swallow the capsule after ten attempts, the research 
procedure will be terminated. 
 
The capsule will be administered by operators trained in the procedure. With an upgraded 
imaging console for improved ease of use, the operator can both administer the capsule 
and control the system as opposed to the previous design that requires separate capsule 
and system operators. The compact system design will also significantly improve ease 
of equipment transport to and from facilities for procedures.  A clinician will always be 
available during the procedure for consultation or advice if any problems are 
encountered. 
 
The imaging procedure starts after the operator confirms that the capsule has been 
swallowed (about 20 cm from the subject’s incisor). The distance from the incisors will 
be established via marks on the outer sheath of the tether. OCT images of the esophagus 
will be obtained as the capsule is descending between the stomach and upper 
esophageal sphincter. The subject may be asked to take additional sips of water during 
the procedure to assist in the motion of the capsule as it passes through the lower 
esophageal sphincter. Imaging will be performed in the same manner as in our other 
current IRB approved tethered capsule endomicroscopy studies. The capsule position 
will be controlled manually via the tether outside of the subject’s mouth by the catheter 
operator. Recorded real time OCT images displayed on the monitor and distance marks 
on the tether will be used for confirmation of capsule position in the esophagus. After the 
imaging procedure is finalized the catheter operator will remove the capsule from the 
esophagus by gently pulling the tether. 
 
The capsule may be repositioned for imaging up to 4 times up and down the 
esophagus. The subject may be asked to swallow a different size capsule 
 
to obtain the best distal esophageal 
images. It is expected that the maximum experimental time including swallowing the 
capsule, the imaging procedure, and removal of the capsule will take approximately 20 
minutes in total. Subjects will not be asked to swallow more than 2 capsules during any 
procedure. 
 
If the study subject wants to stop for any reason, at any time during the procedure or 
should the physician/clinical staff at any point feel that the health and well being of 
the subject is compromised, image acquisition will be immediately suspended, and the 
capsule catheter removed.  
 
FOLLOW UP: 
 
After the imaging procedure, the subject will be asked a set of questions regarding 
tolerability of the procedure before leaving the clinic.  
 
An investigator will also assess the quality of the recorded images and movies obtained 
with each exam after the imaging is completed. OCT images will be analyzed at a later 

Wellman Center for Photomedicine 
MGH 
Pilot study for imaging of the esophagus using a tethered capsule OCT endomicroscopy in the 
Primary Care setting 
 
 
 
 
time and will be used for research purposes only. They will not be used for any diagnostic 
purposes. After analysis of the data, the PI might alert the PCP to some findings and will 
discuss the relevance of those findings.  
 
Investigators and study staff will meet with physicians and clinic staff regularly to assess 
study procedures and troubleshoot any issues that might have arisen regarding 
recruiting, consenting, the imaging procedure, or any other component of this pilot study.  
 
E. COSTS 
 
The experimental procedure will be done at no cost to the subject or his/her insurance 
company and patients will not be responsible for any costs incurred as part of 
participating in this study.  
 
All subjects will be offered a gift certificate in the amount of $50 as compensation for 
their time.  
 
F. BIOSTATISTICAL ANALYSIS 
 
This is a feasibility study in order to estimate subject participation rates, study time 
requirements, and general participant feedback. We will use this information to design a 
larger, more comprehensive clinical study for general population screening. 
 
G. RISKS AND DISCOMFORT 
 
We have performed over 120 such procedures without any unanticipated adverse events 
or device malfunction.  
 
This OCT endoscopy capsule is similar to other approved video endoscopy capsules. 
 
Capsule endoscopy of the esophagus was approved by the FDA in November 2004. It 
has been offered as an alternative to EGD for screening patients with chronic reflux 
and those with a known history of Barrett’s esophagus. Capsule endoscopy (Givens 
G2, OMOM Capsule Endoscope) does not require sedation and it is generally well 
tolerated by the majority of patients. Capsule endoscopy imaging is a safe procedure 
that carries few risks. Some of the risks associated with capsule endoscopy are 
symptomatic capsule retention and aspiration. For normal patients no cases of retention 
or aspiration have been reported. Retention rates have been reported as 1% and 
mainly in patients with strictures. Only a  few cases of aspiration have been reported, 
mostly in older patients. In our study we will use a tethered capsule and strictures are an 
exclusion criteria. Retention and aspiration are highly unlikely. In the unlikely event that 
retention does occur, it is expected that the capsule will pass through the GI tract. In the 
event that the capsule does not pass through the GI tract, X-rays will be taken and the 
capsule will be removed via endoscopy. 
 
It is expected that tethered capsule endomicroscopy will have risks and discomfort 
similar to the approved endoscopy capsules. In the unlikely event that the capsule is 
disconnected from the tether, it is expected that any component of the capsule will be 
able to pass through the GI tract since the OCT capsule’s diameter and length are 

Wellman Center for Photomedicine 
MGH 
Pilot study for imaging of the esophagus using a tethered capsule OCT endomicroscopy in the 
Primary Care setting 
 
 
 
 
comparable to those of FDA-approved, commercially available capsule endoscopes 
that are swallowed and allowed to pass through the GI tract. 
 
In order to minimize risk, and as a safety precaution, the laser will only be turned on when 
the endomicroscope is within the esophagus. The system is operated by trained and 
experienced operators and the laser is only turned on once the capsule operator confirms 
that the capsule has been swallowed and is within the esophagus. 
 
In order to minimize the potential risk of confidentiality, the acquired OCT data and 
all other patient information will be assigned a subject number unique to this 
study. All other patient personal information will be removed. A master log will be 
maintained with full names and medical record numbers, which will be secured in the 
research coordinator’s office. This will be accessible only when deemed necessary 
and only to members of the study team. 
 
It is also not anticipated that participation in this pilot study will directly pose any 
psychological risk. 
 
H. POTENTIAL BENEFITS 
 
There are no medical benefits to the study participants. Images acquired during the study 
are only for research purposes and will not inform clinical care. However, if there are any 
findings of esophageal abnormality seen on OCT, the results will be discussed with the 
primary care physician. 
 
I. MONITORING AND QUALITY ASSURANCE 
As the risks associated with this protocol are low, a Data and Safety Monitoring Board will 
not be required. Dr. Tearney, the Principal Investigator of this study will be directly 
responsible for the conduct of the study. Dr. Tearney will be responsible for ensuring that 
the study is conducted according to the IRB-approved protocol and regulations, and for 
protecting the rights, safety and welfare of the subjects. Dr. Tearney has regular scheduled 
meetings with the clinical staff. He will be responsible for monitoring the study and any 
adverse or unanticipated events on a regular basis. Dr. Tearney is also responsible for 
reporting any unexpected or adverse events to the Partners IRB”. 
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Pilot study for imaging of the esophagus using a tethered capsule OCT endomicroscopy in the 
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Primary Care setting 
 
 
 
 
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Wellman Center for Photomedicine 
MGH 
Pilot study for imaging of the esophagus using a tethered capsule OCT endomicroscopy in the 
Primary Care setting