Marginal Ulcer Healing With Low-Thermal Argon Plasma Endoscopic Treatment

NCT06543316 | Recruiting

• 1 other identifier: 2024P002124
• Study Type: interventional
• Target: 100
• Locations: 1 country
• Sites: 1

Brief Summary

The objective of the study is to investigate the treatment of marginal ulcers with Low Thermal plasma in an endoscopic setting. By a treatment of the ulcerated areas with argon plasma with low power settings (\~ 1 W) we hypothesize that the size of the ulcers will shrink, and the healing is accelerated compared to standard of care alone. Patients will benefit from this minimally invasive approach compared to a much more invasive surgical approach that comes with higher risks and hospital stay length time. From a societal and scientific perspective, this study aims to extend the well-documented clinical benefits of plasma technology - from external wound healing to internal ulcer treatment - within an endoscopic framework. The success of this study could pave the way for broader applications of LTP in the treatment of other endoscopically accessible conditions such as peptic ulcers, duodenal ulcers and esophageal ulcers. This advancement has the potential not only to improve patient outcomes through less invasive methods, but also to position LTP as a cornerstone in the future of gastroenterological wound management strategies.

Conditions

Roux-en-y Anastomosis Site; Marginal Ulcer; Marginal Ulcer (Peptic) or Erosion; Ulcer; Ulcer, Gastric; Ulcer Gastrointestinal; Abdominal Pain; Nausea; Vomiting; GastroIntestinal Bleeding; Dysphagia; Ulcer Gastrojejunal

Keywords

Argon Plasma Coagulation; APC; Low-Thermal Argon Plasma Endoscopic Treatment; Endoscopy; RYGB; Roux-en-Y Gastric Bypass; Ulcer Healing

Outcome Measures

Primary Outcomes (1)

• Ulcer Healing Success Rate from baseline endoscopy

  Complete healing or significant reduction in ulcer size, determined by endoscopic evaluation at the first follow-up (4 weeks +/- 1 week) and at the end of the second follow-up period (8 weeks +/- 2 weeks).

  Baseline, 4 weeks, 8 Weeks

Secondary Outcomes (5)

• Comparison of Time to Ulcer Healing between LTP and SOC groups

  Baseline, 4 weeks, 8 weeks

• Improvement of Tissue Oxygenation at Ulcer Site in LTP treatment group

  Baseline, 4 weeks, 8 weeks

• Presence of Procedure-Related Adverse Events

  Baseline, up to 8 weeks

• Clinical Improvement of Gastrointestinal Symptoms

  Baseline, 8 Weeks

• Change in quality of life score from baseline using the 12 item Short Form Survey (SF-12)

  Baseline, 8 Weeks

Study Arms (2)

Low Thermal Plasma (LTP)

ACTIVE COMPARATOR

Patients randomized to this group will receive LTP treatment of the ulcer in addition to SOC (PPI administration).

Procedure: Low Thermal Plasma (LTP) Treatment; Other: Standard of Care Ulcer Treatment (typically PPI Administration)

Standard of Care (SOC) PPI Administration

ACTIVE COMPARATOR

Patients randomized to this group will receive only the SOC treatment (PPI administration).

Other: Standard of Care Ulcer Treatment (typically PPI Administration)

Interventions

Low Thermal Plasma (LTP) Treatment PROCEDURE

For patients randomized to the LTP group, the first LTP treatment will be administered during the initial esophagogastroduodenoscopy (EGD) using a single-use 2.3 mm filtered argon plasma coagulation (FiAPC probe). The argon plasma will be applied at low power settings (\~1 W) to the ulcerated areas using pulsed APC effect 0.1.

Also known as: LTP

Low Thermal Plasma (LTP)

Standard of Care Ulcer Treatment (typically PPI Administration) OTHER

Standard of care for treatment of ulcers is administration of a proton pump inhibitor (PPI). For patients in the SOC group whose ulcers have not healed completely by the second follow-up at 8 weeks, crossover to LTP treatment will be offered. This treatment will follow the same procedure as the initial LTP treatment.

Also known as: PPI

Low Thermal Plasma (LTP); Standard of Care (SOC) PPI Administration

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Subjects aged 18 years and above, inclusive of both males and females.
• Patients with a history of Roux-en-Y gastric bypass (RYGB) presenting symptoms indicative of marginal ulcers (MUs) such as abdominal pain, nausea, vomiting, gastrointestinal bleeding, or dysphagia.
• Subjects must be scheduled for an EGD for the evaluation of these symptoms.
• Marginal ulcers confirmed during the initial EGD.
• Willingness to adhere to the SOC treatment, which includes PPIs.
• Subjects able to tolerate repeated endoscopic procedures.
• Capacity for providing informed consent and understanding of study requirements.
• Willingness and ability to attend required follow-up assessments at 4 weeks (+/- 1 week) and 8 weeks (+/- 2 weeks).

You may not qualify if:

• Inability to provide informed consent.
• Unwillingness to undergo repeated endoscopies.
• Inability or unwillingness to comply with the SOC.
• Current use of systemic antibiotics.
• Any condition deemed by the investigator to compromise the safety of undergoing an endoscopic procedure.
• Pregnancy, lactation, or absence of reliable contraception in women of childbearing potential.
• Current enrollment in another investigational trial with potential to interfere with this study's endpoint analyses.

Sponsors & Collaborators

• Christopher C. Thompson, MD, MSc: lead
• Erbe USA Incorporated: collaborator

Study Sites (1)

Brigham and Women's Hospital

Boston, Massachusetts, 02115, United States

RECRUITING

Related Publications (30)

• Angrisani L, Santonicola A, Iovino P, Ramos A, Shikora S, Kow L. Bariatric Surgery Survey 2018: Similarities and Disparities Among the 5 IFSO Chapters. Obes Surg. 2021 May;31(5):1937-1948. doi: 10.1007/s11695-020-05207-7. Epub 2021 Jan 12.

  PMID: 33432483 BACKGROUND

• Sapala JA, Wood MH, Sapala MA, Flake TM Jr. Marginal ulcer after gastric bypass: a prospective 3-year study of 173 patients. Obes Surg. 1998 Oct;8(5):505-16. doi: 10.1381/096089298765554061.

  PMID: 9819081 BACKGROUND

• Coblijn UK, Goucham AB, Lagarde SM, Kuiken SD, van Wagensveld BA. Development of ulcer disease after Roux-en-Y gastric bypass, incidence, risk factors, and patient presentation: a systematic review. Obes Surg. 2014 Feb;24(2):299-309. doi: 10.1007/s11695-013-1118-5.

  PMID: 24234733 BACKGROUND

• Steinemann DC, Bueter M, Schiesser M, Amygdalos I, Clavien PA, Nocito A. Management of anastomotic ulcers after Roux-en-Y gastric bypass: results of an international survey. Obes Surg. 2014 May;24(5):741-6. doi: 10.1007/s11695-013-1152-3.

  PMID: 24347350 BACKGROUND

• Choi J, Polistena C. Management of Marginal Ulceration. In: Camacho D, Zundel N, eds. Complications in Bariatric Surgery. Cham: Springer International Publishing; Imprint: Springer; 2018: 45-58

  BACKGROUND

• Carr WR, Mahawar KK, Balupuri S, Small PK. An evidence-based algorithm for the management of marginal ulcers following Roux-en-Y gastric bypass. Obes Surg. 2014 Sep;24(9):1520-7. doi: 10.1007/s11695-014-1293-z.

  PMID: 24851857 BACKGROUND

• Adamovich I, Agarwal S, Ahedo E et al. The 2022 Plasma Roadmap: low temperature plasma science and technology. Plasma Sources Sci. Technol. 2022; 55: 373001

  BACKGROUND

• Chuangsuwanich A, Assadamongkol T, Boonyawan D. The Healing Effect of Low-Temperature Atmospheric-Pressure Plasma in Pressure Ulcer: A Randomized Controlled Trial. Int J Low Extrem Wounds. 2016 Dec;15(4):313-319. doi: 10.1177/1534734616665046. Epub 2016 Sep 20.

  PMID: 27581113 BACKGROUND

• Mirpour S, Fathollah S, Mansouri P, Larijani B, Ghoranneviss M, Mohajeri Tehrani M, Amini MR. Cold atmospheric plasma as an effective method to treat diabetic foot ulcers: A randomized clinical trial. Sci Rep. 2020 Jun 26;10(1):10440. doi: 10.1038/s41598-020-67232-x.

  PMID: 32591594 BACKGROUND

• Hartwig S, Preissner S, Voss JO, Hertel M, Doll C, Waluga R, Raguse JD. The feasibility of cold atmospheric plasma in the treatment of complicated wounds in cranio-maxillo-facial surgery. J Craniomaxillofac Surg. 2017 Oct;45(10):1724-1730. doi: 10.1016/j.jcms.2017.07.008. Epub 2017 Jul 27.

  PMID: 28843407 BACKGROUND

• Isbary G, Morfill G, Schmidt HU, Georgi M, Ramrath K, Heinlin J, Karrer S, Landthaler M, Shimizu T, Steffes B, Bunk W, Monetti R, Zimmermann JL, Pompl R, Stolz W. A first prospective randomized controlled trial to decrease bacterial load using cold atmospheric argon plasma on chronic wounds in patients. Br J Dermatol. 2010 Jul;163(1):78-82. doi: 10.1111/j.1365-2133.2010.09744.x. Epub 2010 Mar 5.

  PMID: 20222930 BACKGROUND

• Abu Rached N, Kley S, Storck M, Meyer T, Stucker M. Cold Plasma Therapy in Chronic Wounds-A Multicenter, Randomized Controlled Clinical Trial (Plasma on Chronic Wounds for Epidermal Regeneration Study): Preliminary Results. J Clin Med. 2023 Aug 4;12(15):5121. doi: 10.3390/jcm12155121.

  PMID: 37568525 BACKGROUND

• Bekeschus S, von Woedtke T, Emmert S, Schmidt A. Medical gas plasma-stimulated wound healing: Evidence and mechanisms. Redox Biol. 2021 Oct;46:102116. doi: 10.1016/j.redox.2021.102116. Epub 2021 Aug 28.

  PMID: 34474394 BACKGROUND

• Graves DB. The emerging role of reactive oxygen and nitrogen species in redox biology and some implications for plasma applications to medicine and biology. Plasma Sources Sci. Technol. 2012; 45: 263001

  BACKGROUND

• Gao J, Wang L, Xia C, Yang X, Cao Z, Zheng L, Ko R, Shen C, Yang C, Cheng C. Cold atmospheric plasma promotes different types of superficial skin erosion wounds healing. Int Wound J. 2019 Oct;16(5):1103-1111. doi: 10.1111/iwj.13161. Epub 2019 Jun 17.

  PMID: 31207094 BACKGROUND

• Amini MR, Sheikh Hosseini M, Fatollah S, Mirpour S, Ghoranneviss M, Larijani B, Mohajeri-Tehrani MR, Khorramizadeh MR. Beneficial effects of cold atmospheric plasma on inflammatory phase of diabetic foot ulcers; a randomized clinical trial. J Diabetes Metab Disord. 2020 Jul 14;19(2):895-905. doi: 10.1007/s40200-020-00577-2. eCollection 2020 Dec.

  PMID: 33520811 BACKGROUND

• Pekshev AV, Shekhter AB, Vagapov AB, Sharapov NA, Vanin AF. Study of plasma-chemical NO-containing gas flow for treatment of wounds and inflammatory processes. Nitric Oxide. 2018 Feb 28;73:74-80. doi: 10.1016/j.niox.2017.06.002. Epub 2017 Jun 26.

  PMID: 28602888 BACKGROUND

• Schmidt A, Woedtke TV, Stenzel J, Lindner T, Polei S, Vollmar B, Bekeschus S. One Year Follow-Up Risk Assessment in SKH-1 Mice and Wounds Treated with an Argon Plasma Jet. Int J Mol Sci. 2017 Apr 19;18(4):868. doi: 10.3390/ijms18040868.

  PMID: 28422070 BACKGROUND

• Metelmann H-R, Vu TT, Do HT et al. Scar formation of laser skin lesions after cold atmospheric pressure plasma (CAP) treatment: A clinical long term observation. Clinical Plasma Medicine 2013; 1: 30-35

  BACKGROUND

• Rutkowski R, Daeschlein G, von Woedtke T, Smeets R, Gosau M, Metelmann HR. Long-term Risk Assessment for Medical Application of Cold Atmospheric Pressure Plasma. Diagnostics (Basel). 2020 Apr 11;10(4):210. doi: 10.3390/diagnostics10040210.

  PMID: 32290487 BACKGROUND

• Winter J, Brandenburg R, Weltmann K-D. Atmospheric pressure plasma jets: an overview of devices and new directions. Plasma Sources Sci. Technol. 2015; 24: 64001

  BACKGROUND

• Grund KE, Zindel C, Farin G. [Argon plasma coagulation through a flexible endoscope. Evaluation of a new therapeutic method after 1606 uses]. Dtsch Med Wochenschr. 1997 Apr 4;122(14):432-8. doi: 10.1055/s-2008-1047634. German.

  PMID: 9138921 BACKGROUND

• Zenker M. Argon plasma coagulation. GMS Krankenhhyg Interdiszip. 2008 Nov 3;3(1):Doc15.

  PMID: 20204117 BACKGROUND

• Eickhoff A, Jakobs R, Schilling D, Hartmann D, Weickert U, Enderle MD, Eickhoff JC, Riemann JF. Prospective nonrandomized comparison of two modes of argon beamer (APC) tumor desobstruction: effectiveness of the new pulsed APC versus forced APC. Endoscopy. 2007 Jul;39(7):637-42. doi: 10.1055/s-2007-966571.

  PMID: 17611919 BACKGROUND

• Kwan V, Bourke MJ, Williams SJ, Gillespie PE, Murray MA, Kaffes AJ, Henriquez MS, Chan RO. Argon plasma coagulation in the management of symptomatic gastrointestinal vascular lesions: experience in 100 consecutive patients with long-term follow-up. Am J Gastroenterol. 2006 Jan;101(1):58-63. doi: 10.1111/j.1572-0241.2006.00370.x.

  PMID: 16405534 BACKGROUND

• Vargo JJ. Clinical applications of the argon plasma coagulator. Gastrointest Endosc. 2004 Jan;59(1):81-8. doi: 10.1016/s0016-5107(03)02296-x. No abstract available.

  PMID: 14722558 BACKGROUND

• Grund KE, Straub T, Farin G. New haemostatic techniques: argon plasma coagulation. Baillieres Best Pract Res Clin Gastroenterol. 1999 Apr;13(1):67-84. doi: 10.1053/bega.1999.0009.

  PMID: 11030635 BACKGROUND

• 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.

  PMID: 8081915 BACKGROUND

• Weiss M, Utz R, Ackermann M et al. Characterization of a non-thermally operated electrosurgical argon plasma source by electron spin resonance spectroscopy. Plasma Process Polym 2019; 16: 1800150

  BACKGROUND

• Weiss M, Arnholdt M, Hissnauer A, Fischer I, Schonfisch B, Andress J, Gerstner S, Dannehl D, Bosmuller H, Staebler A, Brucker SY, Henes M. Tissue-preserving treatment with non-invasive physical plasma of cervical intraepithelial neoplasia-a prospective controlled clinical trial. Front Med (Lausanne). 2023 Aug 15;10:1242732. doi: 10.3389/fmed.2023.1242732. eCollection 2023.

  PMID: 37654659 BACKGROUND

MeSH Terms

Conditions

Peptic Ulcer; Ulcer; Stomach Ulcer; Abdominal Pain; Nausea; Vomiting; Gastrointestinal Hemorrhage; Deglutition Disorders

Interventions

Long-Term Potentiation; Therapeutics

Condition Hierarchy (Ancestors)

Duodenal Diseases; Intestinal Diseases; Gastrointestinal Diseases; Digestive System Diseases; Stomach Diseases; Pathologic Processes; Pathological Conditions, Signs and Symptoms; Pain; Neurologic Manifestations; Signs and Symptoms; Signs and Symptoms, Digestive; Hemorrhage; Esophageal Diseases; Pharyngeal Diseases; Otorhinolaryngologic Diseases

Intervention Hierarchy (Ancestors)

Neuronal Plasticity; Nervous System Physiological Phenomena; Musculoskeletal and Neural Physiological Phenomena

Study Officials

• Christopher C. Thompson, MD, MSc

  Brigham and Womens Hospital

  PRINCIPAL INVESTIGATOR

Central Study Contacts

Michele B Ryan, MS

CONTACT

617-525-8266; mryan@bwh.harvard.edu

Samantha Geltz

CONTACT

617-732-5174; sgeltz@bwh.harvard.edu

Study Design

• Study Type: interventional
• Phase: not applicable
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: CROSSOVER
• Sponsor Type: OTHER
• Responsible Party: SPONSOR INVESTIGATOR
• PI Title: Director of Endoscopy

Model Details: Randomized, two-arm, crossover clinical study

Study Record Dates

• First Submitted: August 2, 2024
• First Posted: August 9, 2024
• Study Start: March 4, 2025
• Primary Completion: February 1, 2026
• Study Completion (Estimated): April 30, 2027
• Last Updated: August 5, 2025

Record last verified: 2025-07

Data Sharing

• IPD Sharing: Will share
• Shared Documents: STUDY PROTOCOL, ICF, CSR
• Time Frame: 12 months after publication.
• Access Criteria: IPD requests should be made directly to the PI who will determine feasibility of the request. Institutional data transfer agreement will need to be executed to share data.

Locations

US (1)