Evaluation of ArTificial Intelligence System (Gi-Genius) for adenoMa dEtection in Lynch Syndrome. (Timely)

Evaluation of ArTificial Intelligence System (Gi-Genius) for adenoMa dEtection in Lynch Syndrome. A Randomized, Parallel, Multicenter, Controlled Trial. TIMELY Study.

The purpose of this study is to assess if artificial intelligence aid colonoscopy colonoscopy is superior to conventional colonoscopy for the detection of adenomas during surveillance colonoscopy in patients with Lynch syndrome.

Study Overview

• Status: Recruiting
• Conditions: Lynch Syndrome
• Intervention / Treatment: Device: Gi Genius, Medtronic; Other: White light standart colonoscopy

Detailed Description

To compare the performance of white-light colonoscopy (HD-WLE) versus white-light + CAD (CAD) for detection of adenomas (1:1 ratio). The CAD system will include an artificial intelligence-based medical device (GI Genius, Medtronic) trained to process colonoscopy images and superimpose them, in real time, on the endoscopy display as a green box over suspected lesion. An adequate bowel preparation and minimum withdrawal time of 6 min will be required. Colonoscopies will be performed by experienced endoscopists and with high-definition scopes. Lesions will be collected, and histopathology findings used as the reference standard. The primary outcome of this trial will be the mean number of adenomas per colonoscopy (APC).

• Study Type: Interventional
• Enrollment (Anticipated): 404
• Phase: Not Applicable

Contacts and Locations

• Study Contact: Name: Maria Pellise, Phd; Phone Number: 2675 +34 932275400; Email: mpellise@clinic.cat

Study Locations

• Spain
  • Barcelona, Spain, 08036
    • Recruiting
    • María Pellisé. MD. PhD.
    • Contact: María Pellisé, MD. PhD.; Phone Number: 2675 +34 932275400; Email: mpellise@clinic.cat
  • Barcelona, Spain, 08036
    • Recruiting
    • Oswaldo ortiz
    • Contact: Oswaldo ortiz; Phone Number: +34691371417; Email: oaortiz@clinic.cat

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

• Age ≥18 years with a proven pathogenic germline variant in one of the MMR genes (MLH1, MSH2, MSH6) or Epcam deletion who are under surveillance colonoscopy.

Exclusion Criteria:

• Previous history of total colectomy,
• Concomitant inflammatory bowel disease,
• Inability or refuse to sign the informed consent,
• Previous colonoscopy < 12 months.
• Inadequate bowel preparation.
• Incomplete procedure.
• PMS2 mutation carriers

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Diagnostic
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Double

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Active Comparator: CAD arm; Patients allocated to CAD arm will receive during colonoscopy withdrawal high definition white light endoscopy aided with artificial intelligence device (Gi Genius, Medtronic)	Device: Gi Genius, Medtronic; GI geniusTM (Medtronic) is an artificial intelligence device designed and validated on a dataset of white-light endoscopy videos from high-quality randomized controlled trials for the detection of colorectal lesions during colonoscopy. Based on a deep learning system using convolutional neural networks, GI genius works in real-time side-to-side with the gastroenterologist during colonoscopy highlighting the presence of precancerous lesions with a visual marker (green box) in real time and designed to be integrated with the majority of colonoscopies.
Placebo Comparator: WLE arm; Patients allocated to WLE arm will receive during colonoscopy withdrawal high definition white light endoscopy as standart of care.	Other: White light standart colonoscopy; High definition white light endoscopy will be used during the scope withdrawal

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Mean number of adenomas per colonoscopy	Compare mean number of adenomas in both arms calculated by dividing the total number of adenomas detected by the total number of colonoscopies in each arm	18 months

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Withdrawal time	time spent on inspection, from the cecum to endoscope extraction through the anus, excluding the time needed for therapeutic measures (including polypectomy).	18 months
Mean number of polyps per colonoscopy	Compare mean number of polyps in both arms calculated by dividing the total number of polyps (including serrated lesions and adenomas) detected by the total number of colonoscopies in each arm	18 months
Adenoma detection rate	proportion of individuals undergoing a complete colonoscopy who had at least one adenoma detected between two arms.	18 months
Polyp detection rate	proportion of individuals undergoing a complete colonoscopy who had at least one polyp detected between two arms.	18 months
False positives in CAD arm	Combination of: Lesions detected by CAD (>2s green box) after an adequate inspection with a high confidence optical diagnosis negative for neoplasia made by the endoscopist.; Lesions detected by CAD (>2s green box) after an adequate inspection resected by the endoscopist and with a clinically non-significant histology.	18 months
Mean number of non-clinically significant removed lesions	Lesions removed and with a histology of normal or inflammatory mucosa or removed diminutive recto-sigmoid polyps with a histology of hyperplastic	18 months
Subjective endoscopist measures	Questionary addresing the easiness and satisfaction of the procedure, detection of lesions and performance of artificial intelligence will be filled in by each endoscopist	18 months

Collaborators and Investigators

• Sponsor: Hospital Clinic of Barcelona
• Collaborators: European Society of Gastrointestinal Endoscopy

Publications and helpful links

General Publications

• Haraldsdottir S, Rafnar T, Frankel WL, Einarsdottir S, Sigurdsson A, Hampel H, Snaebjornsson P, Masson G, Weng D, Arngrimsson R, Kehr B, Yilmaz A, Haraldsson S, Sulem P, Stefansson T, Shields PG, Sigurdsson F, Bekaii-Saab T, Moller PH, Steinarsdottir M, Alexiusdottir K, Hitchins M, Pritchard CC, de la Chapelle A, Jonasson JG, Goldberg RM, Stefansson K. Comprehensive population-wide analysis of Lynch syndrome in Iceland reveals founder mutations in MSH6 and PMS2. Nat Commun. 2017 May 3;8:14755. doi: 10.1038/ncomms14755.
• Huneburg R, Lammert F, Rabe C, Rahner N, Kahl P, Buttner R, Propping P, Sauerbruch T, Lamberti C. Chromocolonoscopy detects more adenomas than white light colonoscopy or narrow band imaging colonoscopy in hereditary nonpolyposis colorectal cancer screening. Endoscopy. 2009 Apr;41(4):316-22. doi: 10.1055/s-0028-1119628. Epub 2009 Apr 1.
• Rahmi G, Lecomte T, Malka D, Maniere T, Le Rhun M, Guimbaud R, Lapalus MG, Le Sidaner A, Moussata D, Caron O, Barbieux JP, Gaudric M, Coron E, Barange K, Ponchon T, Sautereau D, Samaha E, Saurin JC, Chaussade S, Laurent-Puig P, Chatellier G, Cellier C. Impact of chromoscopy on adenoma detection in patients with Lynch syndrome: a prospective, multicenter, blinded, tandem colonoscopy study. Am J Gastroenterol. 2015 Feb;110(2):288-98. doi: 10.1038/ajg.2014.423. Epub 2015 Jan 20.
• East JE, Suzuki N, Stavrinidis M, Guenther T, Thomas HJ, Saunders BP. Narrow band imaging for colonoscopic surveillance in hereditary non-polyposis colorectal cancer. Gut. 2008 Jan;57(1):65-70. doi: 10.1136/gut.2007.128926. Epub 2007 Aug 6.
• Rijcken FE, Hollema H, Kleibeuker JH. Proximal adenomas in hereditary non-polyposis colorectal cancer are prone to rapid malignant transformation. Gut. 2002 Mar;50(3):382-6. doi: 10.1136/gut.50.3.382.
• Rondagh EJ, Gulikers S, Gomez-Garcia EB, Vanlingen Y, Detisch Y, Winkens B, Vasen HF, Masclee AA, Sanduleanu S. Nonpolypoid colorectal neoplasms: a challenge in endoscopic surveillance of patients with Lynch syndrome. Endoscopy. 2013;45(4):257-64. doi: 10.1055/s-0032-1326195. Epub 2013 Feb 25.
• van Leerdam ME, Roos VH, van Hooft JE, Balaguer F, Dekker E, Kaminski MF, Latchford A, Neumann H, Ricciardiello L, Rupinska M, Saurin JC, Tanis PJ, Wagner A, Jover R, Pellise M. Endoscopic management of Lynch syndrome and of familial risk of colorectal cancer: European Society of Gastrointestinal Endoscopy (ESGE) Guideline. Endoscopy. 2019 Nov;51(11):1082-1093. doi: 10.1055/a-1016-4977. Epub 2019 Oct 9.
• Sanchez A, Roos VH, Navarro M, Pineda M, Caballol B, Moreno L, Carballal S, Rodriguez-Alonso L, Ramon Y Cajal T, Llort G, Pinol V, Lopez-Fernandez A, Salces I, Pico MD, Rivas L, Bujanda L, Garzon M, Pizarro A, Martinez de Castro E, Lopez-Arias MJ, Poves C, Garau C, Rodriguez-Alcalde D, Herraiz M, Alvarez-Urrutia C, Dacal A, Carrillo-Palau M, Cid L, Ponce M, Barreiro-Alonso E, Saperas E, Aguirre E, Romero C, Bastiaansen B, Gonzalez-Acosta M, Morales-Romero B, Ocana T, Rivero-Sanchez L, Jung G, Bessa X, Cubiella J, Jover R, Rodriguez-Moranta F, Balmana J, Brunet J, Castells A, Dekker E, Capella G, Serra-Burriel M, Moreira L, Pellise M, Balaguer F. Quality of Colonoscopy Is Associated With Adenoma Detection and Postcolonoscopy Colorectal Cancer Prevention in Lynch Syndrome. Clin Gastroenterol Hepatol. 2022 Mar;20(3):611-621.e9. doi: 10.1016/j.cgh.2020.11.002. Epub 2020 Nov 3.
• Rivero-Sanchez L, Arnau-Collell C, Herrero J, Remedios D, Cubiella J, Garcia-Cougil M, Alvarez V, Albeniz E, Calvo P, Gordillo J, Puig I, Lopez-Vicente J, Huerta A, Lopez-Ceron M, Salces I, Penas B, Parejo S, Rodriguez de Santiago E, Herraiz M, Carretero C, Gimeno-Garcia AZ, Saperas E, Alvarez-Urturi C, Moreira R, Rodriguez de Miguel C, Ocana T, Moreira L, Carballal S, Sanchez A, Jung G, Castells A, Llach J, Balaguer F, Pellise M; EndoCAR group from Spanish Gastroenterology Association (AEG) and Spanish Society of Digestive Endoscopy (SEED). White-Light Endoscopy Is Adequate for Lynch Syndrome Surveillance in a Randomized and Noninferiority Study. Gastroenterology. 2020 Mar;158(4):895-904.e1. doi: 10.1053/j.gastro.2019.09.003. Epub 2019 Sep 12.
• Repici A, Badalamenti M, Maselli R, Correale L, Radaelli F, Rondonotti E, Ferrara E, Spadaccini M, Alkandari A, Fugazza A, Anderloni A, Galtieri PA, Pellegatta G, Carrara S, Di Leo M, Craviotto V, Lamonaca L, Lorenzetti R, Andrealli A, Antonelli G, Wallace M, Sharma P, Rosch T, Hassan C. Efficacy of Real-Time Computer-Aided Detection of Colorectal Neoplasia in a Randomized Trial. Gastroenterology. 2020 Aug;159(2):512-520.e7. doi: 10.1053/j.gastro.2020.04.062. Epub 2020 May 1.
• Hassan C, Spadaccini M, Iannone A, Maselli R, Jovani M, Chandrasekar VT, Antonelli G, Yu H, Areia M, Dinis-Ribeiro M, Bhandari P, Sharma P, Rex DK, Rosch T, Wallace M, Repici A. Performance of artificial intelligence in colonoscopy for adenoma and polyp detection: a systematic review and meta-analysis. Gastrointest Endosc. 2021 Jan;93(1):77-85.e6. doi: 10.1016/j.gie.2020.06.059. Epub 2020 Jun 26.
• Kaminski MF, Thomas-Gibson S, Bugajski M, Bretthauer M, Rees CJ, Dekker E, Hoff G, Jover R, Suchanek S, Ferlitsch M, Anderson J, Roesch T, Hultcranz R, Racz I, Kuipers EJ, Garborg K, East JE, Rupinski M, Seip B, Bennett C, Senore C, Minozzi S, Bisschops R, Domagk D, Valori R, Spada C, Hassan C, Dinis-Ribeiro M, Rutter MD. Performance measures for lower gastrointestinal endoscopy: a European Society of Gastrointestinal Endoscopy (ESGE) Quality Improvement Initiative. Endoscopy. 2017 Apr;49(4):378-397. doi: 10.1055/s-0043-103411. Epub 2017 Mar 7.
• IJspeert JE, Bastiaansen BA, van Leerdam ME, Meijer GA, van Eeden S, Sanduleanu S, Schoon EJ, Bisseling TM, Spaander MC, van Lelyveld N, Bargeman M, Wang J, Dekker E; Dutch Workgroup serrAted polypS & Polyposis (WASP). Development and validation of the WASP classification system for optical diagnosis of adenomas, hyperplastic polyps and sessile serrated adenomas/polyps. Gut. 2016 Jun;65(6):963-70. doi: 10.1136/gutjnl-2014-308411. Epub 2015 Mar 9.
• Sano Y, Tanaka S, Kudo SE, Saito S, Matsuda T, Wada Y, Fujii T, Ikematsu H, Uraoka T, Kobayashi N, Nakamura H, Hotta K, Horimatsu T, Sakamoto N, Fu KI, Tsuruta O, Kawano H, Kashida H, Takeuchi Y, Machida H, Kusaka T, Yoshida N, Hirata I, Terai T, Yamano HO, Kaneko K, Nakajima T, Sakamoto T, Yamaguchi Y, Tamai N, Nakano N, Hayashi N, Oka S, Iwatate M, Ishikawa H, Murakami Y, Yoshida S, Saito Y. Narrow-band imaging (NBI) magnifying endoscopic classification of colorectal tumors proposed by the Japan NBI Expert Team. Dig Endosc. 2016 Jul;28(5):526-33. doi: 10.1111/den.12644. Epub 2016 Apr 20.
• Hewett DG, Kaltenbach T, Sano Y, Tanaka S, Saunders BP, Ponchon T, Soetikno R, Rex DK. Validation of a simple classification system for endoscopic diagnosis of small colorectal polyps using narrow-band imaging. Gastroenterology. 2012 Sep;143(3):599-607.e1. doi: 10.1053/j.gastro.2012.05.006. Epub 2012 May 15.
• Dixon MF. Gastrointestinal epithelial neoplasia: Vienna revisited. Gut. 2002 Jul;51(1):130-1. doi: 10.1136/gut.51.1.130.
• Lynch HT, Snyder CL, Shaw TG, Heinen CD, Hitchins MP. Milestones of Lynch syndrome: 1895-2015. Nat Rev Cancer. 2015 Mar;15(3):181-94. doi: 10.1038/nrc3878. Epub 2015 Feb 12.
• de Jong AE, Hendriks YM, Kleibeuker JH, de Boer SY, Cats A, Griffioen G, Nagengast FM, Nelis FG, Rookus MA, Vasen HF. Decrease in mortality in Lynch syndrome families because of surveillance. Gastroenterology. 2006 Mar;130(3):665-71. doi: 10.1053/j.gastro.2005.11.032.
• Jarvinen HJ, Aarnio M, Mustonen H, Aktan-Collan K, Aaltonen LA, Peltomaki P, De La Chapelle A, Mecklin JP. Controlled 15-year trial on screening for colorectal cancer in families with hereditary nonpolyposis colorectal cancer. Gastroenterology. 2000 May;118(5):829-34. doi: 10.1016/s0016-5085(00)70168-5.
• De Jong AE, Morreau H, Van Puijenbroek M, Eilers PH, Wijnen J, Nagengast FM, Griffioen G, Cats A, Menko FH, Kleibeuker JH, Vasen HF. The role of mismatch repair gene defects in the development of adenomas in patients with HNPCC. Gastroenterology. 2004 Jan;126(1):42-8. doi: 10.1053/j.gastro.2003.10.043.
• Endoscopic Classification Review Group. Update on the paris classification of superficial neoplastic lesions in the digestive tract. Endoscopy. 2005 Jun;37(6):570-8. doi: 10.1055/s-2005-861352.
• Nagtegaal ID, Odze RD, Klimstra D, Paradis V, Rugge M, Schirmacher P, Washington KM, Carneiro F, Cree IA; WHO Classification of Tumours Editorial Board. The 2019 WHO classification of tumours of the digestive system. Histopathology. 2020 Jan;76(2):182-188. doi: 10.1111/his.13975. Epub 2019 Nov 13. No abstract available.

Study record dates

Study Major Dates

• Study Start (Actual): September 13, 2021
• Primary Completion (Anticipated): December 1, 2023
• Study Completion (Anticipated): December 1, 2023

Study Registration Dates

• First Submitted: May 21, 2021
• First Submitted That Met QC Criteria: May 26, 2021
• First Posted (Actual): June 2, 2021

Study Record Updates

• Last Update Posted (Actual): March 17, 2022
• Last Update Submitted That Met QC Criteria: March 16, 2022
• Last Verified: March 1, 2022

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Digestive System Diseases; Pathologic Processes; Metabolic Diseases; Neoplasms by Histologic Type; Neoplasms; Neoplasms by Site; Neoplasms, Glandular and Epithelial; Disease; Gastrointestinal Neoplasms; Digestive System Neoplasms; Gastrointestinal Diseases; Genetic Diseases, Inborn; Colonic Diseases; Intestinal Diseases; Intestinal Neoplasms; Colorectal Neoplasms; Neoplastic Syndromes, Hereditary; DNA Repair-Deficiency Disorders; Syndrome; Adenoma; Colorectal Neoplasms, Hereditary Nonpolyposis
• Other Study ID Numbers: Timely

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: No

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No