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

Barrett's Esophagus Without Dysplasia Clinical Trial

Official title:

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

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT03814824
• Other study ID #: 18-0963
• Status: Completed
• Phase: N/A
• Start date: January 23, 2019
• Est. completion date: February 28, 2021

Study information

• Verified date: September 2022
• Source: Northwell Health
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

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

Description:

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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 148
• Est. completion date: February 28, 2021
• Est. primary completion date: May 31, 2020
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

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

Related Conditions & MeSH terms

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

Intervention

Diagnostic Test:
• 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.

Locations

Country	Name	City	State
United States	North Shore University Hospital	Manhasset	New York
United States	Mayo Clinic	Rochester	Minnesota
United States	Mayo Clinic	Scottsdale	Arizona

Sponsors (3)

Lead Sponsor	Collaborator
Northwell Health	Mayo Clinic, NinePoint Medical

Country where clinical trial is conducted

United States, 

References & Publications (27)

Alshelleh M, Inamdar S, McKinley M, Stewart M, Novak JS, Greenberg RE, Sultan K, Devito B, Cheung M, Cerulli MA, Miller LS, Sejpal DV, Vegesna AK, Trindade AJ. Incremental yield of dysplasia detection in Barrett's esophagus using volumetric laser endomicroscopy with and without laser marking compared with a standardized random biopsy protocol. Gastrointest Endosc. 2018 Jul;88(1):35-42. doi: 10.1016/j.gie.2018.01.032. Epub 2018 Feb 2. — View Citation

Alvarez Herrero L, Curvers WL, van Vilsteren FG, Wolfsen H, Ragunath K, Wong Kee Song LM, Mallant-Hent RC, van Oijen A, Scholten P, Schoon EJ, Schenk EB, Weusten BL, Bergman JG. Validation of the Prague C&M classification of Barrett's esophagus in clinical practice. Endoscopy. 2013 Nov;45(11):876-82. doi: 10.1055/s-0033-1344952. Epub 2013 Oct 28. — View Citation

Atkinson C, Singh S, Fisichella PM. Volumetric laser endomicroscopy in the detection of neoplastic lesions of the esophagus. Dig Liver Dis. 2016 Jun;48(6):692. doi: 10.1016/j.dld.2016.02.013. Epub 2016 Mar 2. — View Citation

Bhat SK, McManus DT, Coleman HG, Johnston BT, Cardwell CR, McMenamin U, Bannon F, Hicks B, Kennedy G, Gavin AT, Murray LJ. Oesophageal adenocarcinoma and prior diagnosis of Barrett's oesophagus: a population-based study. Gut. 2015 Jan;64(1):20-5. doi: 10.1136/gutjnl-2013-305506. Epub 2014 Apr 3. — View Citation

Corley DA, Mehtani K, Quesenberry C, Zhao W, de Boer J, Weiss NS. Impact of endoscopic surveillance on mortality from Barrett's esophagus-associated esophageal adenocarcinomas. Gastroenterology. 2013 Aug;145(2):312-9.e1. doi: 10.1053/j.gastro.2013.05.004. Epub 2013 May 11. — View Citation

Evans JA, Poneros JM, Bouma BE, Bressner J, Halpern EF, Shishkov M, Lauwers GY, Mino-Kenudson M, Nishioka NS, Tearney GJ. Optical coherence tomography to identify intramucosal carcinoma and high-grade dysplasia in Barrett's esophagus. Clin Gastroenterol Hepatol. 2006 Jan;4(1):38-43. — View Citation

Jankowski M, Wani S. Diagnostic and Management Implications of Basic Science Advances in Barrett's Esophagus. Curr Treat Options Gastroenterol. 2015 Mar;13(1):16-29. doi: 10.1007/s11938-014-0040-9. — View Citation

Leggett CL, Gorospe E, Owens VL, Anderson M, Lutzke L, Wang KK. Volumetric laser endomicroscopy detects subsquamous Barrett's adenocarcinoma. Am J Gastroenterol. 2014 Feb;109(2):298-9. doi: 10.1038/ajg.2013.422. — View Citation

Leggett CL, Gorospe EC, Chan DK, Muppa P, Owens V, Smyrk TC, Anderson M, Lutzke LS, Tearney G, Wang KK. Comparative diagnostic performance of volumetric laser endomicroscopy and confocal laser endomicroscopy in the detection of dysplasia associated with Barrett's esophagus. Gastrointest Endosc. 2016 May;83(5):880-888.e2. doi: 10.1016/j.gie.2015.08.050. Epub 2015 Sep 3. — View Citation

Levine DS, Haggitt RC, Blount PL, Rabinovitch PS, Rusch VW, Reid BJ. An endoscopic biopsy protocol can differentiate high-grade dysplasia from early adenocarcinoma in Barrett's esophagus. Gastroenterology. 1993 Jul;105(1):40-50. — View Citation

Mashimo H. Subsquamous intestinal metaplasia after ablation of Barrett's esophagus: frequency and importance. Curr Opin Gastroenterol. 2013 Jul;29(4):454-9. doi: 10.1097/MOG.0b013e3283622796. Review. — View Citation

Pohl H, Welch HG. The role of overdiagnosis and reclassification in the marked increase of esophageal adenocarcinoma incidence. J Natl Cancer Inst. 2005 Jan 19;97(2):142-6. — View Citation

Shaheen NJ, Falk GW, Iyer PG, Gerson LB; American College of Gastroenterology. ACG Clinical Guideline: Diagnosis and Management of Barrett's Esophagus. Am J Gastroenterol. 2016 Jan;111(1):30-50; quiz 51. doi: 10.1038/ajg.2015.322. Epub 2015 Nov 3. Erratum in: Am J Gastroenterol. 2016 Jul;111(7):1077. — View Citation

Spechler SJ, Souza RF. Barrett's esophagus. N Engl J Med. 2014 Aug 28;371(9):836-45. doi: 10.1056/NEJMra1314704. Review. — View Citation

Swager AF, Boerwinkel DF, de Bruin DM, Faber DJ, van Leeuwen TG, Weusten BL, Meijer SL, Bergman JJ, Curvers WL. Detection of buried Barrett's glands after radiofrequency ablation with volumetric laser endomicroscopy. Gastrointest Endosc. 2016 Jan;83(1):80-8. doi: 10.1016/j.gie.2015.05.028. Epub 2015 Jun 26. — View Citation

Swager AF, de Groof AJ, Meijer SL, Weusten BL, Curvers WL, Bergman JJ. Feasibility of laser marking in Barrett's esophagus with volumetric laser endomicroscopy: first-in-man pilot study. Gastrointest Endosc. 2017 Sep;86(3):464-472. doi: 10.1016/j.gie.2017.01.030. Epub 2017 Feb 2. — View Citation

Swager AF, Tearney GJ, Leggett CL, van Oijen MGH, Meijer SL, Weusten BL, Curvers WL, Bergman JJGHM. Identification of volumetric laser endomicroscopy features predictive for early neoplasia in Barrett's esophagus using high-quality histological correlation. Gastrointest Endosc. 2017 May;85(5):918-926.e7. doi: 10.1016/j.gie.2016.09.012. Epub 2016 Sep 19. — View Citation

Swager AF, van der Sommen F, Klomp SR, Zinger S, Meijer SL, Schoon EJ, Bergman JJGHM, de With PH, Curvers WL. Computer-aided detection of early Barrett's neoplasia using volumetric laser endomicroscopy. Gastrointest Endosc. 2017 Nov;86(5):839-846. doi: 10.1016/j.gie.2017.03.011. Epub 2017 Mar 16. — View Citation

The Paris endoscopic classification of superficial neoplastic lesions: esophagus, stomach, and colon: November 30 to December 1, 2002. Gastrointest Endosc. 2003 Dec;58(6 Suppl):S3-43. Review. — View Citation

Trindade AJ, George BJ, Berkowitz J, Sejpal DV, McKinley MJ. Volumetric laser endomicroscopy can target neoplasia not detected by conventional endoscopic measures in long segment Barrett's esophagus. Endosc Int Open. 2016 Mar;4(3):E318-22. doi: 10.1055/s-0042-101409. — View Citation

Trindade AJ, Inamdar S, Smith MS, Chang KJ, Leggett CL, Lightdale CJ, Pleskow DK, Sejpal DV, Tearney GJ, Thomas RM, Wallace MB. Volumetric laser endomicroscopy in Barrett's esophagus: interobserver agreement for interpretation of Barrett's esophagus and associated neoplasia among high-frequency users. Gastrointest Endosc. 2017 Jul;86(1):133-139. doi: 10.1016/j.gie.2016.11.026. Epub 2016 Nov 27. — View Citation

Trindade AJ, Inamdar S, Smith MS, Rosen L, Han D, Chang KJ, Leggett CL, Lightdale CJ, Pleskow DK, Sejpal DV, Tearney GJ, Thomas RM, Wallace MB. Learning curve and competence for volumetric laser endomicroscopy in Barrett's esophagus using cumulative sum analysis. Endoscopy. 2018 May;50(5):471-478. doi: 10.1055/s-0043-121569. Epub 2017 Nov 27. Erratum in: Endoscopy. 2018 May;50(5):C10. — View Citation

Trindade AJ, Leggett CL, Chang KJ. Volumetric laser endomicroscopy in the management of Barrett's esophagus. Curr Opin Gastroenterol. 2017 Jul;33(4):254-260. doi: 10.1097/MOG.0000000000000366. Review. — View Citation

Trindade AJ, Sideridis K, Thomas RM. Buried Barrett's Esophagus Presenting as a Subepithelial Nodule. Am J Gastroenterol. 2016 Oct;111(10):1378. doi: 10.1038/ajg.2016.242. — View Citation

Trindade AJ, Smith MS, Pleskow DK. The new kid on the block for advanced imaging in Barrett's esophagus: a review of volumetric laser endomicroscopy. Therap Adv Gastroenterol. 2016 May;9(3):408-16. doi: 10.1177/1756283X16639003. Epub 2016 Mar 21. Review. — View Citation

Trindade AJ, Vamadevan AS, Sejpal DV. Finding a needle in a haystack: use of volumetric laser endomicroscopy in targeting focal dysplasia in long-segment Barrett's esophagus. Gastrointest Endosc. 2015 Oct;82(4):756; discussion 757. doi: 10.1016/j.gie.2015.03.1984. Epub 2015 May 21. — View Citation

Wolfsen HC, Sharma P, Wallace MB, Leggett C, Tearney G, Wang KK. Safety and feasibility of volumetric laser endomicroscopy in patients with Barrett's esophagus (with videos). Gastrointest Endosc. 2015 Oct;82(4):631-40. doi: 10.1016/j.gie.2015.03.1968. Epub 2015 May 6. — View Citation

* Note: There are 27 references in all — Click here to view all references

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	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
Primary	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
Primary	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	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