Clinical trial NCT01034670
Conditions: Gastrointestinal Diseases Gastric (Stomach) Cancer Gastrointestinal Stromal Tumor (GIST)
Sponsor: Stanford University
Start date: 2009-06-01; Completion date: 2017-09-25
Enrollment: 3 participants; Allocation: NA; Intervention model: SINGLE_GROUP

Brief summary:
To develop new methods to detect malignant and premalignant conditions of the gastrointestinal tract.

Detailed description:

Arms: arm 1: imaging performed in conjunction with the regularly scheduled endoscopy during which the newer imaging techniques will be used to detect premalignant conditions. includes wide field fluorescence, microscopy, Raman spectroscopy and/or ultrasound.
Interventions: intervention 1: Dual axis endoscopic microscope intervention 2: wide field fluorescence system intervention 3: CellVizio intervention 4: fluorescent Peptide intervention 5: fluorescein intervention 6: indocyanine green
Intervention descriptions: intervention 1: This is a device that is used in the accessory port of a standard endoscope and allows visualization of microscopic areas of mucosa. intervention 2: This is a modification to the existing narrow band endoscope from Olympus that incorporates different filters on the source and collecting optics to enable fluorescence imaging. It is used as is a standard endoscope. intervention 3: Minimicroscope--this is an FDA approved fiber-based microscope that we will use according to the manufacturers protocols. intervention 4: microdosing; Topical through the endoscope intervention 5: 100 mcg topical intervention 6: 100 mcg topical

Protocol documents:
Prot_000.pdf: 
 
Advanced Gastrointestinal Endoscopic Imaging 
NCT01034670 
September 15, 2021 
1. 
PURPOSE OF THE STUDY 
a. 
Brief Summary 
Develop new methods to detect and manage malignant and premalignant conditions of 
the gastrointestinal tract. 
b. 
Objectives 
Current endoscopy techniques cannot reliably differentiate between early premalignant 
conditions and normal mucosa. We hope to develop new techniques to improve this and 
will be combining macroscopic and microscopic imaging tools with molecular probes. 
 
To improve visualization during the endoscopic procedure, we will be using an overtube 
(a sleeve that fits over the scope) and a cap (a small clear plastic cap that is attached to 
the tip of the endoscope). The physician performing the procedure will subjectively rate 
the stability of the endoscope tip and the quality of the visualization with the cap and 
overtube. 
 
We also hope to assess techniques to better perform polypectomy (which is performed for 
the purpose of reducing risk of colorectal cancer). We will assess the utility of EverLift, 
which is a Submucosal Lifting Agent. EverLift has been FDA approved for the indication 
of endoscopic procedures for "submucosal lift of polyps, adenomas, early-stage cancers, 
or other gastrointestinal lesions prior to excision with snare or other appropriate 
endoscopic device." We will be assessing the ability to EverLift to provide adequate 
submucosal lift, in accordance with tis FDA indication. We will be using snare or other 
appropriate endoscopic devices to perform polypectomy, and will be assessing the 
completeness of excision of the polyps and adenomas. 
 
We will also be including patients with active or recent COVID-19 to study whether the 
infection may have an impact. This will have importance in helping manage COVID-19 
patients in the future. We will be looking for residual COVID DNA in biopsies in 
patients who have active or recent COVID-19. 
c. 
Rationale for Research in Humans 
There are no adequate animal endoscopy models to allow detection of premalignant 
endoscopic findings, and the molecular probes are being developed for human targets 


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such that cross reactivity with animal markers are unlikely. Cross reactivity with target 
molecules on mouse, and other animals. cells will be evaluated to see if there is a suitable 
animal model. There are also no effective animal endoscopy models that would allow 
real-time assessment of efficacy of polypectomy. 
2. 
STUDY PROCEDURES 
a. 
Procedures 
Participants will be undergoing medically necessary endoscopy procedures or will be 
receiving regularly scheduled care in the gastroenterology or general surgery 
departments. Patients that are not undergoing medically necessary endoscopy procedures 
will have three tubes of blood (30ml) collected for the study and will not undergo any of 
the other portions of the protocol described below. 
 
The remainder of the study will consist of additional imaging performed in conjunction 
with the regularly scheduled endoscopy during which the newer imaging techniques will 
be used to detect premalignant conditions. This will include wide field fluorescence, 
microscopy, Ramanspectroscopy, computerized image analysis, and/or ultrasound. In 
addition, two or three tubes of blood (20-30 ml) will be collected from study subjects. 
 
For the wide field fluorescence we will use an Olympus endoscope that can operate in the 
white light mode like a standard endoscope, and in a fluorescence mode where the input 
light is filtered as is the collected light. This exam will not require an additional 
endoscope. 
 
If a polyp is removed as part of routine clinical care during the endoscopy procedure, we 
will add tranexamic acid to the injection fluid that is used to facilitate the polyp removal 
in half of the cases. This will allow us to assess whether the tranexamic acid improves 
imaging by eliminating trace amounts of bleeding at the polyp site. 
 
If a polyp <=3mm is to be removed as part of routine clinical care during the endoscopy 
procedure, we will remove half of the polyps using cold biopsy forceps and the other half 
using cold snare. Biopsies will be performed at the margins of the polypectomy site. This 
will allow us to assess whether cold biopsy forceps or cold snare is more effective at 
adequately removing polyps. While biopsies are routinely performed in clinical practice 
to check for completeness of resection, the biopsies performed at the margins of the 
polypectomy site are done for research purposes. However, biopsies of the margins are of 
minimal increased risk. 
 
If a polyp >3mm is to be removed as part of routine clinical care during the endoscopy 
procedure, we will remove half of the polyps using an submucosal injection agent 
(EverLift) and the other half of the polyps without a submucosal injection agent. EverLift 
will be used to provide submucosal lift of the polyp or gastrointestinal lesion prior to 
excision with snare or other appropriate endoscopic device, as consistent with its FDA 
approval. Biopsies will be performed at the margins of the polypectomy site. This will 
allow us to assess whether using an injection agent increases the completeness of polyp 
resection as well as improve intra-procedural hemostasis. While biopsies are routinely 


September 15, 2021 
 
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performed in clinical practice to check for completeness of resection, the biopsies 
performed at the margins of the polypectomy site are done for research purposes. 
However, biopsies of the margins are of minimal increased risk. 
 
For the Raman spectroscopy we will put a Raman fiber optic scope into the instrument 
channel of an Olympus endoscope. This procedure will only use a single endoscope. 
 
This Raman scope is deployed like any other instrument that fits into the channel of the 
endoscope. But since we will need to biopsy the tissues after Raman spectroscopic 
examination, the procedure will take more time as we put the Raman scope into the 
endoscope, remove it and put the biopsy forceps into the channel. The Raman 
spectroscopic imaging will involve using a 785 nm laser with a 1mm spot size. We have 
calculated the maximum permissible exposure to the tissue and we will be using a low 
power laser illumination that is under the maximum permissible exposure to tissue as 
recommended by the ANSI standards. Additionally, a safety mechanism is in place where 
the laser illumination is controlled through a shutter that can only be opened while 
acquiring spectra with the acquisition software we intend to use to operate our device. 
 
For the microendoscopy we will put a minimicroscope, also called aminiprobe, into the 
instrument channel of an Olympus endoscope. This procedure will also use only a single 
endoscope. These minimicroscopes are deployed like any other instrument that fits into 
the channel of the endoscope. But since we will need to biopsy the tissues after 
microscopic examination, the procedure will take more time as we put the microscope 
into the endoscope, remove it and put the biopsy forceps into the channel. 
 
As part of this program we will be developing miniaturized ultrasound systems. As these 
are developed and we can better describe them to the IRB, we will amend our protocols 
with sufficient detail that the panel can review these instruments. No experimental 
ultrasound will be performed until we have approval for these new tools from the IRB. 
 
We will use an overtube (a plastic sleeve that fits over the scope)and a cap (a small clear 
plastic piece fitted to the end of the endoscope)to stabilize the endoscope tip during the 
procedure. The physician performing the procedure will rate the stability of the 
endoscope tip with the cap and overtube. 
 
When endoscopic biopsies are performed for clinical purposes during the endoscopy, a 
portion of the biopsy material will also be analyzed using the microscope and biomarker 
assays like western blots or immunohistochemistry or immunofluorescence imaging. 
 
We intend to take one biopsy of normal tissue per study that the patient enrolls in. The 
physician, Shai Friedland will take a biopsy using the same standard procedures for 
taking tissues for biopsy when taking tissue samples for histological assessment. The 
additional tissue collected will impact the study by determining what useful targeting 
biomarkers are generally overexpressed in normal vs tumor areas. The tissues will be 
evaluated for various biomarkers overexpressed on normal vs tumor tissue. This will be 
very important in helping us determine how to better target these tumors in the future. 
 


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We will also be including patients with active or recent COVID-19 to study whether the 
infection may have an impact. We will be looking for residual COVID DNA in biopsies 
in patients who have active or recent COVID-19. This will have importance in helping 
manage COVID-19patients in the future. 
b. 
Procedure Risks 
The participants will have their regularly scheduled endoscopy procedures and the 
research component will consist of an additional 5-15 minutes during which the advanced 
imaging techniques will be used to attempt to detect premalignant lesions. The new 
imaging tools are either developed by companies that make ultrasound equipment (wide 
field fluorescence by Olympus) and involve only slight modifications to existing systems, 
or they are microscopes designed for clinical use 
c. 
Use of Deception in the Study 
No deception 
d. 
Use of Audio and Video Recordings 
Endoscopy videos will be obtained. There will be no patient-identifying information on 
these videos. The videos may be shown at scientific meetings and will be kept as part of 
the study data. 
e. 
Alternative Procedures or Courses of Treatment 
The alternative is not to participate. In this case only the standard medically indicated 
endoscopic procedure will be performed. 
f. 
Will it be possible to continue the more (most) appropriate therapy for the 
participant(s) after the conclusion of the study? 
Yes. All patients will continue to receive their appropriate medical therapy. 
g. 
Study Endpoint(s) 
The study duration is limited to the endoscopic procedure. 
3. 
BACKGROUND  
a. 
Past Experimental and/or Clinical Findings 
Prior studies by our group and others have shown that it may be possible to detect 
premalignant lesions using optical probes that selectively enhance the signal tumors of 
the GI. 
b. 
Findings from Past Animal Experiments 
Prior animal experiments have demonstrated that optical detection techniques during 
endoscopy are feasible. 
4. 
RADIOISOTOPES OR RADIATION MACHINES 
N/A 


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5. 
DEVICES USED IN THE STUDY 
a. 
Investigational Devices (Including Commercial Devices Used Off-Label) 
Investigational Device 1 
Name: 
Dual axis endoscopic microscope 
Description: 
This is a device that is used in the accessory port of a standard endoscope 
and allows visualization of microscopic areas of mucosa. 
Significant Risk? (Y/N) 
No 
Rationale for Non-Significant Risk 
low level of light that does not pose a significant risk to tissue 
Investigational Device 2 
Name: 
Wide field fluorescence system 
Description: 
This is a modification to the existing narrow band endoscope from 
Olympus that incorporates different filters on the source and collecting 
optics to enable fluorescence imaging. It is used as is a standard 
endoscope. 
Significant Risk? (Y/N) 
No 
Rationale for Non-Significant Risk 
This instrument is much like a standard endoscope and is used in the same 
way. The only difference is that the emission and excitation sources are 
filtered to enable fluorescence imaging. 
Investigational Device 3 
Name: 
Raman Endoscope 
Description: 
This is a device that is used in the accessory port of a standard endoscope 
and allows visualization of the chemical components intrinsic to the 
tissue, and any FDA approved dyes that are routinely administered during 
endoscopy. 
Significant Risk? (Y/N) 
No 
Rationale for Non-Significant Risk 
The device operates similarly to the other devices that have already been 
used in humans under this IRB protocol as it is being sent through the 
accessory channel of an endoscope. Low levels of light that do not pose a 
significant risk to tissue will be used. Additionally we have installed a 
shutter that only allows the light from the probe to illuminate the tissue 
area during spectral acquisition as an additional safety precaution. 
Investigational Device 3 
Name: 
Dynamically digitizing overtube 
Description: 
This is a flexible sleeve that fits over the endoscope. After advancing the 
endoscope to the appropriate position, application of vacuum to the 
overtube makes it more rigid so that the endoscope tip is stabilized. 
Significant Risk? (Y/N) 
No 
Rationale for Non-Significant Risk 
The risk of trauma to the digestive organs or other adverse events from 
overtube use is very low (< 0.5%). 
Investigational Device 3 
Name: 
Endovigilant CAD 
Description: 
Deep learning-based image analysis software for analyzing endoscopy 
images 
Significant Risk? (Y/N) 
No 
Rationale for Non-Significant Risk 
Image analysis software does not pose a significant risk to patients 
undergoing endoscopic procedure 
Investigational Device 3 
Name: 
Pathfinder Endoscope Cap 
Description: 
This is a short transparent single-use plastic cap that is placed at the tip of 
the endoscope to improve visualization. Caps are commonly used in 
endoscopic procedures. The Pathfinder Endoscope cap is very similar in 
design to existing FDA-cleared caps that are commonly used but is made 
of a slightly thinner plastic to allow it to fit through the Pathfinder 
Overtube. We believe this does not significantly change the risk The risk 
of bleeding or perforation from using a cap is <1 in 5000. 
Significant Risk? (Y/N) 
No 
Rationale for Non-Significant Risk 
Endoscope caps are widely used during endoscopy to improve 
visualization. They are known to pose non-significant risk. They are not 


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intended as an implant not are they used in supporting or sustaining 
human life. The use of these caps does not pose a serious risk to the 
health, safety, or welfare of a subject 
 
b. 
IDE-Exempt Devices 
IND-Exempt Device 1 
Name: 
CellVizio 
Description: 
Minimicroscope--this is an FDA approved fiber-based microscope that we 
will use according to the manufacturers protocols. 
IND-Exempt Device 2 
Name: 
EverLift  
Description: 
We will assess the utility of EverLift, which is a Submucosal Lifting 
Agent. EverLift has been FDA approved for the indication of endoscopic 
procedures for "submucosal lift of polyps, adenomas, early-stage cancers, 
or other gastrointestinal lesions prior to excision with snare or other 
appropriate endoscopic device." It is similar to other submucosal lifting 
agents on the market such as Eleview. The ingredients are primarily 
methylene blue and hydroxyethyl cellulose. Methylene blue is commonly 
used in endoscopic procedures. Given the similarities to the predicate 
device (Eleview), it is felt to have similar safety profile. We will be using 
EverLift in accordance to its indication as written above (taken from the 
FDA approval documentation).   
 
6. 
DRUGS, BIOLOGICS, REAGENTS, OR CHEMICALS USED IN THE STUDY 
a. 
Investigational Drugs, Biologics, Reagents, or Chemicals 
N/A 
b. 
Commercial Drugs, Biologics, Reagents, or Chemicals 
Commercial Product 1 
Name: 
tranexamic acid 
Dosage: 
100mg 
7. 
DISINFECTION PROCEDURES FOR MEDICAL EQUIPMENT USED ON BOTH HUMANS AND 
ANIMALS 
N/A 
8. 
PARTICIPANT POPULATION 
a. 
Planned Enrollment 
1,000 patients at VA Palo Alto and 100 patients at Stanford will have a variety of cancers 
(esophagus, stomach, colon) and premalignant conditions (polyps, etc.) of the esophagus, 
stomach and colon. Up to 1/2 of the patients will be normal. We plan to compare the 
imaging results in normal patients, patients with premalignant conditions and patients 
with gastrointestinal cancers. 
 
In addition, up to 50 patients at VA Palo Alto and 50 patients at Stanford who are treated 
in the gastroenterology and surgery departments will be enrolled for just the blood draw 
component of the study. 


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We will also be including patients with active or recent COVID-19 to study whether the 
infection may have an impact. We will be looking for residual COVID DNA in biopsies 
in patients who have active or recent COVID-19. This will have importance in helping 
manage COVID-19 patients in the future. 
b. 
Age, Gender, and Ethnic Background 
Age 18+, both genders and all ethnic backgrounds. 
c. 
Vulnerable Populations 
No vulnerable subjects 
d. 
Rationale for Exclusion of Certain Populations 
Children are not included because the endoscopy units only serve adult patients 
e. 
Stanford Populations 
N/A 
f. 
Healthy Volunteers 
N/A 
g. 
Recruitment Details 
Patients who are scheduled for endoscopy by one of the investigators will be asked if 
they are interested in participating in the study. 
 
In addition, patients treated in the gastroenterology and surgery departments who have 
undergone endoscopy by one of the investigators will be asked if they are interested in 
participating in the blood draw component of the study. 
h. 
Eligibility Criteria 
i. 
Inclusion Criteria 
The study will be open to all patients undergoing endoscopy that do not have 
exclusion criteria. 
ii. 
Exclusion Criteria 
Patients with unstable vital signs will not be included. 
i. 
Screening Procedures 
Patients scheduled for endoscopy by one of the investigators will be asked if they would 
like to participate in the study. If they are interested, then they will be enrolled. 
j. 
Participation in Multiple Protocols 
We will ask all patients if they are participating in any other studies. If they are 
participating in any other study then we will ask them for more information to determine 


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whether there could be any harm from participating in both studies and if there is then 
they will not be enrolled. 
k. 
Payments to Participants 
no payment 
l. 
Costs to Participants 
no costs 
m. 
Planned Duration of the Study 
We expect the total study duration would be 17 years. 
 
The study will take 5-15 minutes during the regularly scheduled endoscopy. 
 
Analysis of data will take approximately 2 years. 
9. 
RISKS 
a. 
Potential Risks 
i. 
Investigational devices 
There is a very low (< 1 in 5000) risk of perforation of the gastrointestinal tract and a low 
(< 1 in 1000) risk of bleeding from operating the investigational microscope device 
during endoscopy. The nano-devices pose little to no risk as they are composed of inert 
gold and are cleared from the body within 24 hours therefore qualifying as a non-implant 
and there is no evidence of them crossing over into the circulation after extensive animal 
studies (see attached papers sent to Anastasia Doherty).There is a very low(<1 in 5000) 
of perforation or bleeding from the Pathfinder Endoscope Cap used in the study. 
ii. 
Investigational drugs 
There is a very low (< 1 in 5000) risk of an allergic reaction to tranexamic acid. The risk 
of other adverse events such as infection or thrombosis are very low with submucosal 
injection as performed in the study. 
iii. 
Commercially available drugs, biologics, reagents or chemicals 
N/A 
iv. 
Procedures 
There is a very low (< 1 in 5000) risk of perforation of the gastrointestinal tract and a low 
(< 1 in 1000) risk of bleeding during the study portion of the endoscopy. 
 
There is a very low risk of an adverse event from the blood draw (< 1 in 1000). 
 
There is a very low risk of an adverse event from biopsies of resection site (<1 in 1000 
risk of bleeding, <1 in 1000 risk of infection). There is a very low risk of adverse event 
from polypectomy of a small polyp - there is no evidence to suggest either technique 


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(cold snare or cold biopsy) is safer than the other. There is also no evidence to suggest 
either technique (submucosal lift versus no submucosal lift) influences the safety of the 
procedure. 
v. 
Radioisotopes/radiation-producing machines 
N/A 
vi. 
Physical well-being 
With the exception of the rare potential complications described above, we do not expect 
any harm to the participants' physical well-being. 
vii. 
Psychological well-being 
The patients are sedated during their medically-necessary endoscopy procedures and we 
do not expect any harm to their psychological health. 
viii. 
Economic well-being 
no expected effect 
ix. 
Social well-being 
no expected effect 
x. 
Overall evaluation of risk 
Low 
b. 
International Research Risk Procedures 
N/A 
c. 
Procedures to Minimize Risk 
All of the patients undergo continuous vital signs monitoring by trained endoscopy nurses 
during the procedure. They are monitored continuously during the procedure and during 
recovery for any evidence of complications. 
d. 
Study Conclusion 
The study will be completed during the endoscopy procedure. 
e. 
Data Safety Monitoring Plan (DSMC) 
i. 
Data and/or events subject to review 
Complications from the endoscopy, including any complications that could 
potentially be due to the study. 
ii. 
Person(s) responsible for Data and Safety Monitoring 
The investigators and protocol director will be responsible for monitoring the data. 
iii. 
Frequency of DSMB meetings 


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Possible adverse events will be reviewed daily. 
iv. 
Specific triggers or stopping rules 
If any adverse events occur, the protocol will be suspended until the PD investigates 
the event and determines whether or not it is related to the study. 
v. 
DSMB Reporting 
The PD will inform the IRB if any adverse events relating to the study occur. 
vi. 
Will the Protocol Director be the only monitoring entity? (Y/N) 
Yes 
f. 
Risks to Special Populations 
N/A 
10. 
BENEFITS 
This study will potentially improve our ability to detect (and therefore treat) premalignant and 
malignant disorders of the GI tract. 
11. 
PRIVACY AND CONFIDENTIALITY 
All participant information and specimens are handled in compliance with the Health Insurance 
Portability and Accountability Act (HIPAA) and privacy policies of Stanford University, Stanford 
Health Care, and Stanford Children’s Health.