Neoplasms

Digestive System Diseases

All Conditions

Symptoms and General Pathology

Barrett Esophagus

Hyperplasia

Precancerous Conditions

Esophageal Diseases

Gastrointestinal Diseases

VLE (Volumetric laser endomicroscopy) performed alone, followed by IRIS (Intelligent real-time image segmentation) imaging.

VLE (Volumetric laser endomicroscopy) performed with IRIS (Intelligent real-time image segmentation) imaging, followed by VLE alone.

IRIS has the ability to identify and display three specific images features that may correlate with dysplasia that are represented in different color schemes.

IRIS (Intelligent real-time image segmentation)

VLE uses infrared light to produce real time high-resolution cross sectional imaging of the esophagus.

VLE (Volumetric laser endomicroscopy)

Arvind Trindade, MD

This is a prospective randomized clinical trial examining how IRIS (Intelligent Real-time Image Segmentation) affects biopsy patterns in VLE (Volumetric laser endomicroscopy).

Patients will undergo a VLE exam with and without IRIS per the standard of care. All patients regardless of the study participation in this study would receive VLE with and without IRIS clinically. They will be randomized into VLE without IRIS first vs VLE with IRIS first. The BUDDY Randomization System, provided for use by the Northwell Health Biostatistics Unit, will be used for this. Randomization will be stratified based on prior diagnosis of dysplasia. The order in which the patient is randomized to will be recorded on the case report form. There will be concealed allocation as the study coordinator performing the randomization will not know the order of the next allocation.

Both VLE and IRIS imaging are being performed as standard of care. However, randomization of the order allows for comparison of the two. Regions of interest (ROI) will be recorded using a full scan and recorded on the case report form. The time to identification of ROIs will also be recorded. Each group will then cross over such that the VLE without IRIS group will then have IRIS turned on. ROI will then be recorded for each group based on full scans. A consensus ROI will be recorded based on the two exams. Only one ROI per centimeter will be allowed to avoid overlapping of laser marks. In addition, VLE without IRIS and IRIS marks within 75 frames of each other or 2 hours (on a clock face orientation) will be considered the same target.

Laser marking will then be performed. A double laser mark will be applied to all IRIS ROIs. A single laser mark will be applied to VLE ROIs. Targeted biopsies will be taken of all laser marks and placed in separate biopsy jars. Biopsies will be taken in between the laser marks for double laser marked areas. For single laser marks, biopsies will be taken on either side of the laser mark. Resection of visible lesions will then occur per standard of care (if present) followed by random biopsies of the segment. Random biopsies are pinch biopsies every 1 cm the length of the Barrett's in a 4 quadrant fashion per gastrointestinal society guidelines. There are no additional research biopsies being performed outside this study. The targeted biopsies are based on the VLE features that are suspicious for dysplasia and thus standard of care. The other biopsies being performed here are random biopsies which are also being performed for standard of care. Biopsied samples will be stored per standard of care procedures per the pathology department. They will not be stored for future research purposes.

Following each procedure, the physician will be asked a series of Likert Scale questions to assess the utility of IRIS in that procedure, including how it impacts their confidence in image interpretation, their ability to assimilate data more easily and quickly, and their overall perception of the technology.

Although, the VLE with IRIS and VLE without IRIS are being performed as standard of care, all adverse events will be recorded and reported to the IRB.

All data will be entered into a central encrypted REDCap database.

Expert pathologists who specialize in gastrointestinal pathology will read the histology. A second gastrointestinal pathologist will confirm any histologic diagnosis of dysplasia. This is the standard of care at Northwell Health and academic medical centers per gastrointestinal society guidelines.

All procedures (upper endoscopy, volumetric laser endomicroscopy, and IRIS enhanced VLE) will be performed as standard of care. The prospective data collection and initial randomization will be the research component. All data collected will be de-identified before being transferred into a database. This will be kept in a safe place that is only accessible to the research team.

Volumetric Laser Endomicroscopy With Intelligent Real-time Image Segmentation (IRIS)

Volumetric Laser Endomicroscopy With Intelligent Real-time Image Segmentation (IRIS): a Multi-center Randomized Prospective Study

The length of time required to fully assess and interpret the results of a VLE scan. Time will be a surrogate for ease of interpretation. Time will be recorded from start of image interpretation to the end of image interpretation. Length of the Barrett's segment will be taken into account (time per cm of Barrett's) when comparing this outcome between patients and procedures.

The length of time required to fully assess and interpret the results of a VLE scan. Time will be a surrogate for ease of interpretation. Time will be recorded from start of image interpretation to the end of image interpretation. Length of Barrett's will be taken into account (time per cm of Barrett's) when comparing this outcome between patients and procedures.

Biopsy yield (in terms of dysplasia present versus not present) of subjects with IRIS biopsies (double laser mark) will be compared to subjects with VLE without IRIS biopsies (single laser mark) and subjects with random biopsies (taken every 1cm in a four quadrant fashion throughout the length of the Barrett's).

NinePoint Medical

Mayo Clinic

Northwell Health

VLE (Volumetric laser endomicroscopy) performed alone, followed by IRIS (Intelligent real-time image segmentation) imaging.

IRIS (Intelligent real-time image segmentation): IRIS has the ability to identify and display three specific images features that may correlate with dysplasia that are represented in different color schemes.

VLE (Volumetric laser endomicroscopy): VLE uses infrared light to produce real time high-resolution cross sectional imaging of the esophagus.

VLE Without IRIS

VLE (Volumetric laser endomicroscopy) performed with IRIS (Intelligent real-time image segmentation) imaging, followed by VLE alone.

IRIS (Intelligent real-time image segmentation): IRIS has the ability to identify and display three specific images features that may correlate with dysplasia that are represented in different color schemes.

VLE (Volumetric laser endomicroscopy): VLE uses infrared light to produce real time high-resolution cross sectional imaging of the esophagus.

VLE With IRIS

VLE Without IRIS, Followed by VLE With IRIS

VLE With IRIS, Followed by VLE Without IRIS

Total

Age, Categorical

Sex: Female, Male

Race and Ethnicity were not collected from any participant.

Race and Ethnicity Not Collected

By utilizing expert users, we're unable to assess the impact of IRIS on novice interpretation. We also utilized a surveillance biopsy protocol that avoided areas of laser marking to avoid confounding and were thus unable to compare VLE-related dysplasia detection to that which would have occurred in the standardized biopsy protocol. Finally, although we did randomize the order of interpretation, it is not possible to eliminate all bias from a subjective interpretation paradigm.

Dr. Arvind Trindade

Total interpretation time (VLE/IRIS)

Interpretation time (VLE alone)

First Interpretation Time

Second Interpretation Time

Time for Image Interpretation (Mean)

Scaled First Interpretation Time

Scaled Second Interpretation Time

Time for Image Interpretation (Mean - Scaled)

Time for Image Interpretation (Median - Scaled)

VLE (Volumetric laser endomicroscopy) performed alone,

VLE (Volumetric laser endomicroscopy): VLE uses infrared light to produce real time high-resolution cross sectional imaging of the esophagus.

VLE (Volumetric laser endomicroscopy) performed with IRIS (Intelligent real-time image segmentation) imaging.

VLE (Volumetric laser endomicroscopy): VLE uses infrared light to produce real time high-resolution cross sectional imaging of the esophagus.

IRIS (Intelligent real-time image segmentation): IRIS has the ability to identify and display three specific images features that may correlate with dysplasia that are represented in different color schemes.

Standardized method of biopsy collection entailing taking biopsies every 1cm of the Barrett's segment in a 4 quadrant fashion, the current standard of care.

Seattle Protocol

Subjects With Dysplasia on Biopsies

Overall Study

Adenocarcinoma

Carcinoma

Neoplasms, Glandular and Epithelial

Neoplasms by Histologic Type

Antineoplastic Agents

All Drugs and Chemicals

Amino Acids

Mechlorethamine

Lysine

Asparagine

GI heptapeptide, Linear, 7 amino acid peptide sequence ASYNYDA with a 5-FITC tag and NH2 terminus. Chemical Formula: Ala1-Ser2-Tyr3-Asn4-Tyr5-Asp6-Ala7-Gly8- Gly9-Gly10-Ser11-Lys12 (5-FITC) -NH213.Investigational Agent Manufacturer: CPC Scientific, 1245 Reamwood Ave, Sunnyvale, CA 94089 Investigational Agent information: Lot Number: 10031701, M.W. 1577.6, 97.2% pure. Stored at -20C Yellow, lyophilized powder in single use amber vials. 5-FITC is light-sensitive, therefore stored protected from light. Manufactured under cGMP with Certificate of Analysis (COA) provided.

GI heptapeptide

You are invited to participate in a research study to develop new ways to look for abnormal areas/tissues of the esophagus. The current endoscopes used to look at the esophagus are very good, but if the area doesn't look different to the naked eye, then the endoscope can't improve on that. The investigators are looking at using special fluorescent stains in addition to special endoscopes designed to see abnormal areas that are not obvious to the naked eye. Currently specialized microscopes and fluorescent stains are used in clinical laboratories but it takes several days of processing to get results. It may be very helpful to look for areas to sample for abnormal tissue during the endoscopy procedure.

You are being asked to let us use "fluorescent peptides" with a special endoscope that allow us to "see" of your esophagus with both fluorescent and white light during your upper GI endoscopy procedure to help target your biopsies. Peptides are small chains of amino acids (the building blocks that make up proteins) linked together. Our peptide is a chain of 7 amino acids attached to a fluorescent dye called FITC (like the one used by your eye doctor).

The investigators have prepared special "fluorescent peptides", that will "glow" when a special light is used that should help us separate normal tissue from abnormal tissue. In this study, the investigators will apply the special fluorescent peptides by a spray catheter to your esophagus to help us target you biopsies. Both routine and targeted biopsies will be taken as your endoscopist feels is indicated.

This is a phase 1 study. This means that this is the first time the investigators have used this kind of "fluorescent peptide" in people. The Food and Drug Administration (FDA) has not approved this agent, but is allowing us to test it in this study. The main goal of this study is to see if there are any side effects from using the peptide. Our second goal is to see if the peptide "glows" well and if the investigators can take pictures of the areas that do glow.

This is the first test of this agent, so it won't be used to change how your biopsies are taken nor how your endoscopy is done.

SUMMARY OF STUDY PLAN A Phase I study of the safety of a topically-administered 7-amino acid peptide with a fluorescein analog (5-FITC) label for detecting neoplastic areas of the esophagus is proposed. The study will test the safety of administering this agent (5-FITC-labeled 7-AA peptide) to human subjects undergoing clinically-indicated upper endoscopy and/or endoscopic ultrasound for suspected esophageal adenocarcinoma with or without Barrett's Esophagus or High-Grade dysplasia (HGD) in Barrett's Esophagus. We intend to enroll 25 evaluable subjects. We expect to be able to enroll about 5 subjects per month, so the study should take about 6-9 months to complete.

Subjects will be recruited around their scheduled procedure. The endoscopists performing the procedures are all investigators on this protocol and on the FDA form 1572. Blood for clinical labs and urine for dipstick urinanalysis (and pregnancy test, if applicable) will be collected pre-procedure, along with medical information. Vital signs are monitored throughout the clinical procedure and will be captured on case report forms, so no separate physical exam is necessary. The endoscopy will proceed per UMHS (University of Michigan Health System) standard of care and guidelines for management of Barrett's Esophagus (American College of Gastroenterology, Appendix C). The endoscopist performing the clinical procedure will evaluate the potential risk (if any) for their patient to continue with the procedure or study. The endoscopist will spray the reconstituted 5-FITC-labeled peptide onto the esophageal mucosa through a catheter in the endoscope. Pictures with white-light will be taken with the standard endoscope before and after the peptide application. The Mauna Kea/Cellvizio® or miniprobe , an FDA approved instrument (510(k) ref # K051585) will be passed through the instrument channel of the standard endoscope and used for collecting confocal images of up to two areas where the peptide binds. Biopsies will taken as clinically indicated, including the two places where the confocal images were taken. Data about all clinical biopsies will be collected on case report forms. All biopsies are for clinical care only (not research use) and will be sent for routine histology per UMHS standard of care.

Approximately 24 hours (± 4 hours) post-procedure, blood for clinical labs and urine for dipstick urinanalysis (UA) will be collected to assess for potential effects (if any) from applying the peptide solution. Subjects will receive compensation for the inconvenience of returning for another blood draw. Subjects may be able to have their blood and UA done at a UMHS lab or QUEST Diagnostics Lab closer to their home Subjects will receive compensation for the inconvenience of returning for another blood draw. Subjects may be able to have their blood and UA done at a UMHS lab or QUEST Diagnostics Lab closer to their home orby Michigan Clinical Research Unit to you (MCRU 2U). Additional blood draws for follow up labs may be needed if any significant differences from baseline are seen. Additional compensation will be offered for those blood draws.

Esophageal Protocol for Detection of Neoplasia in the Digestive Tract

A Phase I In-Vivo Esophageal Protocol for Detection of Neoplasia in the Digestive Tract

The study will test the safety of administering this agent to human subjects. Prior to the EGD,subjects will have baseline blood work, urinanalysis via dipstick and urine pregnancy test. Labs for CBC w/ platets, chemistries and liver function tests and (COMP panel). These labs will be to compare to post-procedure levels for any possible side effects. These tests will be repeated 24 hours post peptide application and as needed weekly until labs resolve to normal ranges.

Study title	NCT ID	Conditions	Interventions	Eligibility	Organization
Volumetric Laser Endomicroscopy With Intelligent Real-time Image Segmentation (IRIS)	NCT03814824	Barrett's Esoph... Barrett's Esoph... Barrett's Esoph... Barrett's Esoph... Barrett's Esoph...	IRIS (Intellige... VLE (Volumetric...	18 Years -	Northwell Health
Volumetric Laser Endomicroscopy With Intelligent Real-time Image Segmentation (IRIS)	NCT03814824	Barrett's Esoph... Barrett's Esoph... Barrett's Esoph... Barrett's Esoph... Barrett's Esoph...	IRIS (Intellige... VLE (Volumetric...	18 Years -	Northwell Health
Esophageal Protocol for Detection of Neoplasia in the Digestive Tract	NCT01391208	Barrett Esophag... Esophageal Aden...	GI heptapeptide	18 Years -	University of Michigan
Esophageal Protocol for Detection of Neoplasia in the Digestive Tract	NCT01391208	Barrett Esophag... Esophageal Aden...	GI heptapeptide	18 Years -	University of Michigan

Spots Global Cancer Trial Database for barrett's esophagus with high grade dysplasia