Cold Atmospheric Plasma for the Endoscopic Treatment of Duodenal Polyps in Patients With Familial Adenomatous Polyposis (coldAPC)

The objective of this study is to investigate the feasibility for the treatment of precancerous peri-ampullary FAP polyps in the duodenum using low-thermal argonplasma.

Study Overview

• Status: Recruiting
• Conditions: Familial Adenomatous Polyposis; Adenomatous Polyposis Coli; Duodenal Adenoma
• Intervention / Treatment: Device: low energy argonplasma coagulation

Detailed Description

Familial adenomatous polyposis (FAP) is an autosomal dominantly inherited disorder, which results from a germ line mutation in the APC (adenomatous polyposis coli) gene. FAP is characterized by the formation of very high number of colorectal adenomatous polyps which could cause the development of colorectal cancer in the 5th decade of life. After colon surgery patients are still at risk of developing upper GI cancer e.g. in the duodenum. Because of the continuing risk for the development of duodenal cancer, regular endoscopic surveillance is recommended for these patients.

In this study a new APC modality (Precise mode E1) applied for the remission of FAP polyps during routine endoscopic surveillance is suggested. Argonplasma coagulation (APC) is widely used for the ablation and coagulation of superficial lesions in the GI tract. The application of high thermal tissue destroying APC in the duodenum is challenging due to the anatomy of the duodenal wall which is thin and therefore susceptible to thermal damage.

The application of low-thermal argonplasma in the GI tract could be just as useful as it was suggested for the treatment of neoplastic tissue in gynecology. Low-thermal APC using Erbe Standard 3.2 mm FiAPC probe and Precise mode was successfully applied for the remission of cervical intraepithelial neoplasia. The formation of reactive oxygen and nitric oxide species has been discussed as trigger for the effect on neoplasia tissue of low-thermal argonplasma.

Regarding current knowledge this is the first application of this APC modality in the GI tract.

• Study Type: Interventional
• Enrollment (Estimated): 10
• Phase: Not Applicable

Contacts and Locations

• Study Contact: Name: Thomas Rösch, Professor; Phone Number: 50098 +49407410; Email: t.roesch@uke.de
• Study Contact Backup: Name: Tania Ruppenthal; Phone Number: 50089 +49407410; Email: t.ruppenthal@uke.de

Study Locations

• Germany
  • Hamburg, Germany, 20246
    • Recruiting
    • University Hospital Hamburg-Eppendorf
    • Contact: Thomas Rösch, Professor; Phone Number: 50098 +49407410; Email: t.roesch@uke.de
    • Contact: Tania Ruppenthal; Phone Number: 50089 +49407410; Email: t.ruppenthal@uke.de
    • Principal Investigator: Thomas Rösch, Professor
    • Sub-Investigator: Jocelyn de Heer, PD Dr.

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Adult; Older Adult
• Accepts Healthy Volunteers: No

Description

Inclusion Criteria:

• confirmed FAP disease
• duodenal polyposis with recommendation of a follow-up EGD in 12 months corresponding to stage III (7-8 points) according to Spigelman
• presence of duodenal polyps < 10 mm
• written Informed Consent

Exclusion Criteria:

• presence of lesions that are suspicious of the presence of high-grade dysplasia or carcinoma
• pregnancy or breastfeeding
• severe general illnesses (permanent ASA (American Society of Anesthesiologists) III and IV) who do not prognostically benefit from follow-up, life expectancy < 1 year
• severe coagulopathy
• any visible state of duodenal surface that makes APC treatment impossible, e.g. inflammation, stricture, stenosis or scarring changes/scar areas

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: N/A
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: duodenal polyps <10 mm; low energy argonplasma coagulation	Device: low energy argonplasma coagulation; see above; Other Names: cold APC

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
polyp number	Significant reduction in the number of duodenal polyps at the next follow-up appointment	12 months
polyp size	Significant reduction in the size of duodenal polyps at the next follow-up appointment	12 months

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
acute haematemesis	rate of acute adverse incidents: bleeding	24 hours
acute hemoglobin drop	rate of acute adverse incidents: Hb drop < 2g /dl (grammes per decilitre)	24 hours
acute severe hemoglobin drop	rate of acute adverse incidents: Hb drop = or > 2g /dl (grammes per decilitre)	24 hours
blood transfusion	rate of acute adverse incidents: Hb drop = or > 2g /dl (grammes per decilitre)	24 hours
endoscopic hemostasis	rate of acute adverse incidents: coagulation or clipping	24 hours
treatment of perforation	rate of acute adverse incidents: endoscopic clipping	24 hours
need for surgical intervention	rate of acute adverse incidents: bleeding or perforation which can not be handled by endoscopic treatment	24 hours
acute abdominal pain	rate of acute adverse incidents:pain	24 hours
acute dysphagia	rate of acute adverse incidents: stenosis	24 hours
acute rise of temperature	rate of acute adverse incidents: fever <38°C (degrees Centigrade)	24 hours
EGD (esophago-gastro-duodenoscopy) time	total EGD performing time	during EGD; up to 45 minutes
therapy time	total ablation time in minutes	up to 30 minutes
abdominal pain	abdominal pain assessed by patient survey	4 days
nausea	nausea assessed by patient survey	4 days
feeling of fullness	feeling of fullness assessed by patient survey	4 days
emesis	emesis assessed by patient survey	4 days
signs of bleeding	hematemesis or tar faeces assessed by patient survey	4 days
fever	fever >38°C	4 days
need for physician help	visits in doctor's office or hospital	4 days
success rate	Change in stage/number of points in Spigelman classification compared to the previous examination	12 months
dysphagia	dysphagia caused by duodenal stricture	12 months
balloon dilatations	need for endoscopic dilatation of strictured duodenum	12 months
abdominal pain	general abdominal pain assessed by patient survey	12 months
postprandial pain	postprandial abdominal pain assessed by patient survey	12 months
emesis	regurgitation due to duodenal strictures assessed by EGD	12 months

Collaborators and Investigators

• Sponsor: Universitätsklinikum Hamburg-Eppendorf
• Investigators: Principal Investigator: Thomas Rösch, Professor, Universitätskrankenhaus Hamburg-Eppendorf

Publications and helpful links

General Publications

• Bulow S, Bjork J, Christensen IJ, Fausa O, Jarvinen H, Moesgaard F, Vasen HF; DAF Study Group. Duodenal adenomatosis in familial adenomatous polyposis. Gut. 2004 Mar;53(3):381-6. doi: 10.1136/gut.2003.027771.
• Spigelman AD, Williams CB, Talbot IC, Domizio P, Phillips RK. Upper gastrointestinal cancer in patients with familial adenomatous polyposis. Lancet. 1989 Sep 30;2(8666):783-5. doi: 10.1016/s0140-6736(89)90840-4.
• van Leerdam ME, Roos VH, van Hooft JE, Dekker E, Jover R, Kaminski MF, Latchford A, Neumann H, Pellise M, Saurin JC, Tanis PJ, Wagner A, Balaguer F, Ricciardiello L. Endoscopic management of polyposis syndromes: European Society of Gastrointestinal Endoscopy (ESGE) Guideline. Endoscopy. 2019 Sep;51(9):877-895. doi: 10.1055/a-0965-0605. Epub 2019 Jul 23.
• Aelvoet AS, Buttitta F, Ricciardiello L, Dekker E. Management of familial adenomatous polyposis and MUTYH-associated polyposis; new insights. Best Pract Res Clin Gastroenterol. 2022 Jun-Aug;58-59:101793. doi: 10.1016/j.bpg.2022.101793. Epub 2022 Mar 16.
• Half E, Bercovich D, Rozen P. Familial adenomatous polyposis. Orphanet J Rare Dis. 2009 Oct 12;4:22. doi: 10.1186/1750-1172-4-22.
• Ghorbanoghli Z, Bastiaansen BA, Langers AM, Nagengast FM, Poley JW, Hardwick JC, Koornstra JJ, Sanduleanu S, de Vos Tot Nederveen Cappel WH, Witteman BJ, Morreau H, Dekker E, Vasen HF. Extracolonic cancer risk in Dutch patients with APC (adenomatous polyposis coli)-associated polyposis. J Med Genet. 2018 Jan;55(1):11-14. doi: 10.1136/jmedgenet-2017-104545. Epub 2017 May 10.
• Kadmon M, Tandara A, Herfarth C. Duodenal adenomatosis in familial adenomatous polyposis coli. A review of the literature and results from the Heidelberg Polyposis Register. Int J Colorectal Dis. 2001 Apr;16(2):63-75. doi: 10.1007/s003840100290.
• Bjork J, Akerbrant H, Iselius L, Bergman A, Engwall Y, Wahlstrom J, Martinsson T, Nordling M, Hultcrantz R. Periampullary adenomas and adenocarcinomas in familial adenomatous polyposis: cumulative risks and APC gene mutations. Gastroenterology. 2001 Nov;121(5):1127-35. doi: 10.1053/gast.2001.28707.
• Manner H. Thermal ablative therapies in the gastrointestinal tract. Curr Opin Gastroenterol. 2023 Sep 1;39(5):370-374. doi: 10.1097/MOG.0000000000000954. Epub 2023 Jun 22.
• Manner H. Argon plasma coagulation therapy. Curr Opin Gastroenterol. 2008 Sep;24(5):612-6. doi: 10.1097/MOG.0b013e32830bf825.
• Martusevich AK, Surovegina AV, Bocharin IV, Nazarov VV, Minenko IA, Artamonov MY. Cold Argon Athmospheric Plasma for Biomedicine: Biological Effects, Applications and Possibilities. Antioxidants (Basel). 2022 Jun 27;11(7):1262. doi: 10.3390/antiox11071262.
• Marzi J, Stope MB, Henes M, Koch A, Wenzel T, Holl M, Layland SL, Neis F, Bosmuller H, Ruoff F, Templin M, Kramer B, Staebler A, Barz J, Carvajal Berrio DA, Enderle M, Loskill PM, Brucker SY, Schenke-Layland K, Weiss M. Noninvasive Physical Plasma as Innovative and Tissue-Preserving Therapy for Women Positive for Cervical Intraepithelial Neoplasia. Cancers (Basel). 2022 Apr 12;14(8):1933. doi: 10.3390/cancers14081933.
• Grund KE, Storek D, Farin G. Endoscopic argon plasma coagulation (APC) first clinical experiences in flexible endoscopy. Endosc Surg Allied Technol. 1994 Feb;2(1):42-6.
• Karamanolis G, Triantafyllou K, Tsiamoulos Z, Polymeros D, Kalli T, Misailidis N, Ladas SD. Argon plasma coagulation has a long-lasting therapeutic effect in patients with chronic radiation proctitis. Endoscopy. 2009 Jun;41(6):529-31. doi: 10.1055/s-0029-1214726. Epub 2009 May 13.
• Peng M, Guo X, Yi F, Shao X, Wang L, Wu Y, Wang C, Zhu M, Bian O, Ibrahim M, Chawla S, Qi X. Endoscopic treatment for gastric antral vascular ectasia. Ther Adv Chronic Dis. 2021 Aug 12;12:20406223211039696. doi: 10.1177/20406223211039696. eCollection 2021.
• Swanson E, Mahgoub A, MacDonald R, Shaukat A. Medical and endoscopic therapies for angiodysplasia and gastric antral vascular ectasia: a systematic review. Clin Gastroenterol Hepatol. 2014 Apr;12(4):571-82. doi: 10.1016/j.cgh.2013.08.038. Epub 2013 Sep 5.
• Lienert A, Bagshaw PF. Treatment of duodenal adenomas with endoscopic argon plasma coagulation. ANZ J Surg. 2007 May;77(5):371-3. doi: 10.1111/j.1445-2197.2007.04063.x.
• Manner H, May A, Faerber M, Rabenstein T, Ell C. Safety and efficacy of a new high power argon plasma coagulation system (hp-APC) in lesions of the upper gastrointestinal tract. Dig Liver Dis. 2006 Jul;38(7):471-8. doi: 10.1016/j.dld.2006.03.022. Epub 2006 May 15.
• Jaganmohan S, Lynch PM, Raju RP, Ross WA, Lee JE, Raju GS, Bhutani MS, Fleming JB, Lee JH. Endoscopic management of duodenal adenomas in familial adenomatous polyposis--a single-center experience. Dig Dis Sci. 2012 Mar;57(3):732-7. doi: 10.1007/s10620-011-1917-2. Epub 2011 Sep 30.
• Na HK, Kim DH, Ahn JY, Lee JH, Jung KW, Choi KD, Song HJ, Lee GH, Jung HY. Clinical Outcomes following Endoscopic Treatment for Sporadic Nonampullary Duodenal Adenoma. Dig Dis. 2020;38(5):364-372. doi: 10.1159/000504249. Epub 2020 Jun 9.
• Manner H, Enderle MD, Pech O, May A, Plum N, Riemann JF, Ell C, Eickhoff A. Second-generation argon plasma coagulation: two-center experience with 600 patients. J Gastroenterol Hepatol. 2008 Jun;23(6):872-8. doi: 10.1111/j.1440-1746.2008.05437.x.
• Eickhoff A, Hartmann D, Eickhoff JC, Riemann JF, Enderle MD. Pain sensation and neuromuscular stimulation during argon plasma coagulation in gastrointestinal endoscopy. Surg Endosc. 2008 Jul;22(7):1701-7. doi: 10.1007/s00464-007-9700-3. Epub 2007 Dec 11.
• Amoyel M, Belle A, Dhooge M, Ali EA, Hallit R, Prat F, Dohan A, Terris B, Chaussade S, Coriat R, Barret M. Endoscopic management of non-ampullary duodenal adenomas. Endosc Int Open. 2022 Jan 14;10(1):E96-E108. doi: 10.1055/a-1723-2847. eCollection 2022 Jan.
• Kim GE, Siddiqui UD. Endoscopic Resection Techniques for Duodenal and Ampullary Adenomas. VideoGIE. 2023 Jul 22;8(8):330-335. doi: 10.1016/j.vgie.2023.05.006. eCollection 2023 Aug.

Helpful Links

• German oncological guidelines for colorectal cancer

Study record dates

Study Major Dates

• Study Start (Actual): December 6, 2023
• Primary Completion (Estimated): January 30, 2025
• Study Completion (Estimated): March 2, 2025

Study Registration Dates

• First Submitted: March 14, 2024
• First Submitted That Met QC Criteria: May 23, 2024
• First Posted (Actual): May 30, 2024

Study Record Updates

• Last Update Posted (Actual): May 30, 2024
• Last Update Submitted That Met QC Criteria: May 23, 2024
• Last Verified: May 1, 2024

More Information

Terms related to this study

• Keywords: argon plasma coagulation; Familial Adenomatous Polyposis; FAP; duodenal adenoma; Spigelman classification stage III
• Additional Relevant MeSH Terms: Digestive System Diseases; Neoplasms by Histologic Type; Neoplasms; Neoplasms by Site; Neoplasms, Glandular and Epithelial; Gastrointestinal Neoplasms; Digestive System Neoplasms; Gastrointestinal Diseases; Genetic Diseases, Inborn; Pharyngeal Neoplasms; Otorhinolaryngologic Neoplasms; Head and Neck Neoplasms; Nasopharyngeal Diseases; Pharyngeal Diseases; Stomatognathic Diseases; Otorhinolaryngologic Diseases; Colonic Diseases; Intestinal Diseases; Intestinal Neoplasms; Rectal Diseases; Neoplastic Syndromes, Hereditary; Adenomatous Polyps; Intestinal Polyposis; Nasopharyngeal Neoplasms; Colorectal Neoplasms; Adenoma; Adenomatous Polyposis Coli
• Other Study ID Numbers: 2023-101193-BO-ff

Drug and device information, study documents

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