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

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

Detailed Description
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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.

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

Conditions
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Barrett's Esophagus Without Dysplasia, Barrett's Esophagus With Dysplasia, Barrett's Esophagus With Low Grade Dysplasia, Barrett's Esophagus With High Grade Dysplasia, Barrett's Esophagus With Dysplasia, Unspecified

Intervention / Treatment
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* Diagnostic Test: IRIS (Intelligent real-time image segmentation)
* Diagnostic Test: VLE (Volumetric laser endomicroscopy)


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: 18 years of age or older at the time of informed consent Barrett's esophagus greater than 2 cm in length Undergoing a scheduled upper endoscopy with VLE exam for surveillance as standard of care Exclusion Criteria: Less than 18 years old at the time of informed consent Unable to provide written informed consent Esophageal stenosis/stricture preventing VLE Esophagitis Severe medical comorbidities preventing endoscopy Pregnancy Uncontrolled coagulopathy

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Diagnostic
Allocation: Randomized
Intervention Model: Crossover Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Active Comparator: VLE without IRIS, followed by VLE with IRIS<br>VLE (Volumetric laser endomicroscopy) performed alone, followed by IRIS (Intelligent real-time image segmentation) imaging. | Diagnostic Test: IRIS (Intelligent real-time image segmentation)<br>* IRIS has the ability to identify and display three specific images features that may correlate with dysplasia that are represented in different color schemes.<br>Diagnostic Test: VLE (Volumetric laser endomicroscopy)<br>* VLE uses infrared light to produce real time high-resolution cross sectional imaging of the esophagus.<br>|
| Active Comparator: VLE with IRIS, followed by VLE without IRIS<br>VLE (Volumetric laser endomicroscopy) performed with IRIS (Intelligent real-time image segmentation) imaging, followed by VLE alone. | Diagnostic Test: IRIS (Intelligent real-time image segmentation)<br>* IRIS has the ability to identify and display three specific images features that may correlate with dysplasia that are represented in different color schemes.<br>Diagnostic Test: VLE (Volumetric laser endomicroscopy)<br>* VLE uses infrared light to produce real time high-resolution cross sectional imaging of the esophagus.<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Time for Image Interpretation (Mean) | 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. | Index procedure, up to 1 hour | 
| Time for Image Interpretation (Mean - Scaled) | 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. | Index procedure, up to 1 hour | 
| Time for Image Interpretation (Median - Scaled) | 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. | Index procedure, up to 1 hour | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Subjects With Dysplasia on Biopsies | 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). | Index procedure | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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VLE, Volumetric laser endomicroscopy, IRIS, Intelligent real-time image segmentation, Barrett's Esophagus