Marginal Ulcer Healing With Low-Thermal Argon Plasma Endoscopic Treatment (AMULET)

July 31, 2025 updated by: Christopher C. Thompson, MD, MSc

Accelerated Marginal Ulcer Healing With Low-Thermal Argon Plasma Endoscopic Treatment

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.

Study Overview

Status

Recruiting

Conditions

Intervention / Treatment

Detailed Description

Gastric bypass surgery, specifically Roux-en-Y gastric bypass (RYGB), is the second most common bariatric procedure performed worldwide (29.3%) after sleeve gastrectomy (55.4%). Despite its success in reducing obesity-related conditions, RYGB is associated with the development of marginal ulcers (MUs)-internal wounds at the gastrojejunal anastomosis prone to poor healing. The incidence of MUs in patients post-RYGB ranges widely, reported at 0.6% to 25% in the U.S., with some estimates as high as 34% worldwide due to asymptomatic cases that go undetected unless investigated endoscopically. These ulcers can become chronic and persisting over time, significantly complicating post-surgical outcomes and increasing the risk of severe complications like perforation, which necessitates urgent surgical intervention in approximately 1-2% of cases.

The current standard of care for MUs involves prolonged use of proton pump inhibitors (PPIs), which reduce gastric acidity to promote ulcer healing. However, this approach addresses only one aspect of MU pathophysiology and is limited by several shortcomings. It is often insufficient in preventing recurrence and carries risks of significant side effects, including increased risk of infection, electrolyte imbalances, and potential kidney disease, particularly with long-term use. Standard therapy is 8 weeks high-dose treatment, and a lifelong PPI therapy is considered if success is seen with medical management. For those not responding to 8 weeks of therapy, most advocate for continued PPI treatment with serial endoscopic evaluation, even up to 2 years out from initial diagnosis. Given these challenges, there is an evident need for alternative treatments that can more effectively target the underlying causes of MUs and reduce the reliance on PPIs.

Low-thermal or low-temperature plasma (LTP) represents a significant advance in accelerated wound healing technologies. As the fourth state of matter, physical plasma is used in the field of plasma medicine to treat a variety of medical conditions at atmospheric pressure and temperatures close to body temperature (typically between 20°C and 50°C). Over the past 10 to 15 years, wound healing has been a primary clinical application for LTP, with extensive use demonstrating its clinical efficacy in the treatment of chronic and poorly healing wounds.

The mechanisms by which LTP facilitates wound healing include oxygenation of tissues, activation of growth factors, improvement of microcirculation, reduction of bacterial load in wounds, and devitalization of senescent cells. These effects are primarily achieved by the ionization of argon gas and the generation of reactive oxygen and nitrogen species (RONS) in the gas phase. Clinically, LTP has been applied to a variety of wound types, including pressure ulcers, chronic wounds, and acute wounds, and has demonstrated effectiveness across a range of wound sizes and stages. LTP treatments are particularly noted for their ability to transform chronic wounds into actively healing wounds, thereby altering the physiological state of the wound.

Several studies have rigorously evaluated the safety profile of LTP and confirmed that it does not pose mutagenic or carcinogenic risks. Long-term evaluations have shown no evidence of tumor formation or abnormal tissue architecture in gas plasma-treated animal models, even after extended periods corresponding to 60 human-equivalent years. Patient follow-up studies using advanced imaging techniques have further confirmed the absence of abnormal healing responses, supporting the absence of adverse long-term effects.

Currently, the most common low-thermal plasma sources used to treat external wounds are PlasmaJets and Dielectric Barrier Discharge (DBD) plasma sources. However, the physical dimensions of these devices limit their use in endoscopic applications. This has limited the availability of LTP for the treatment of internal wounds and ulcers.

Argon plasma coagulation (APC) is a technology that has been used in endoscopy for more than three decades. It has demonstrated clinical safety and efficacy in many areas, including bleeding management (e.g., bleeding ulcers), ablation of cancerous tissue, and precise treatment in sensitive areas. It is primarily used in endoscopic procedures with flexible probes, but also in laparoscopic and open surgery settings. The flexible probes are available in various diameters, 1.5 mm, 2.3 mm and 3.2 mm.

APC works by ionizing argon gas with a high-frequency alternating current passed through an electrode. This ionized gas forms a physical plasma that is applied to tissue. Depending on the mode and effect setting, the plasma can be adjusted in power from as low as 1 W to as high as 120 W. At higher power settings (5 W and above), the plasma exhibits a more pronounced thermal effect due to increased current flow through the tissue, facilitating effective coagulation. Conversely, at lower settings below 5 W, a low-thermal plasma effect is achieved, minimizing tissue coagulation through dynamic application and avoiding prolonged exposure to a single spot. As with PlasmaJets and Dielectric Barrier Discharge (DBD) plasma sources, the effectiveness of low-thermal argon plasma is primarily due to the high energy and voltage that generate reactive oxygen and nitrogen species (RONS).

Study Type

Interventional

Enrollment (Estimated)

100

Phase

  • Not Applicable

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Contact

Study Contact Backup

Study Locations

  • United States
    • Massachusetts
      • Boston, Massachusetts, United States, 02115
        • Recruiting
        • Brigham and Women's Hospital
        • Principal Investigator:
          • Christopher C. Thompson, MD, MSc
        • Contact:

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

  • Adult
  • Older Adult

Accepts Healthy Volunteers

No

Description

Inclusion Criteria:

  • 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).

Exclusion Criteria:

  • 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.

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: Treatment
  • Allocation: Randomized
  • Interventional Model: Crossover Assignment
  • Masking: None (Open Label)

Arms and Interventions

Participant Group / Arm
Intervention / Treatment
Active Comparator: Low Thermal Plasma (LTP)
Patients randomized to this group will receive LTP treatment of the ulcer in addition to SOC (PPI administration).
Procedure: Low Thermal Plasma (LTP) Treatment
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.
Other Names:
  • LTP
Other: Standard of Care Ulcer Treatment (typically PPI Administration)
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.
Other Names:
  • PPI
Active Comparator: Standard of Care (SOC) PPI Administration
Patients randomized to this group will receive only the SOC treatment (PPI administration).
Other: Standard of Care Ulcer Treatment (typically PPI Administration)
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.
Other Names:
  • PPI

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Ulcer Healing Success Rate from baseline endoscopy
Time Frame: Baseline, 4 weeks, 8 Weeks
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 Outcome Measures

Outcome Measure
Measure Description
Time Frame
Comparison of Time to Ulcer Healing between LTP and SOC groups
Time Frame: Baseline, 4 weeks, 8 weeks
To measure the time in days from initial treatment to complete ulcer healing in both treatment phases, accounting for the initial ulcer size.
Baseline, 4 weeks, 8 weeks
Improvement of Tissue Oxygenation at Ulcer Site in LTP treatment group
Time Frame: Baseline, 4 weeks, 8 weeks
To measure the change of the tissue oxygenation in the ulcerated area directly after the LTP treatment and at the follow-up visits. Level of tissue oxygenation will be compared to a baseline measurement before the initial LTP treatment. Level of tissue oxygenation measured by light absorption with an image sensor (ELUXEO Vision System, Fujifilm).
Baseline, 4 weeks, 8 weeks
Presence of Procedure-Related Adverse Events
Time Frame: Baseline, up to 8 weeks
To evaluate the safety profile of LTP by recording the presence of adverse events such as bleeding, perforation, and infection in both initial and crossover phases from during the procedure up to 8 weeks post-procedure.
Baseline, up to 8 weeks
Clinical Improvement of Gastrointestinal Symptoms
Time Frame: Baseline, 8 Weeks
Change in Gastrointestinal Symptoms from Baseline Using the gastrointestinal symptom rating scale (GSRS). This has a seven-point graded Likert-type scale where 1 represents absence of troublesome symptoms and 7 represents very troublesome symptoms.
Baseline, 8 Weeks
Change in quality of life score from baseline using the 12 item Short Form Survey (SF-12)
Time Frame: Baseline, 8 Weeks
Comparison of quality of life scores from baseline to 4 weeks post-treatment using the SF-12 scoring system. Scores range from 0 to 100, with higher scores indicating better physical and mental health functioning. A score of 50 or less has been recommended as a cut-off to determine a physical condition in the Physical Health Composite Score (PCS) section; while a score of 42 or less may be indicative of 'clinical depression' Mental Health Composite Score (MCS) section.
Baseline, 8 Weeks

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

Christopher C. Thompson, MD, MSc

Collaborators

Erbe USA Incorporated

Investigators

  • Principal Investigator: Christopher C. Thompson, MD, MSc, Brigham and Womens Hospital

Publications and helpful links

The person responsible for entering information about the study voluntarily provides these publications. These may be about anything related to the study.

General Publications

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start (Actual)

March 4, 2025

Primary Completion (Estimated)

February 1, 2026

Study Completion (Estimated)

April 30, 2027

Study Registration Dates

First Submitted

August 2, 2024

First Submitted That Met QC Criteria

August 6, 2024

First Posted (Actual)

August 9, 2024

Study Record Updates

Last Update Posted (Actual)

August 5, 2025

Last Update Submitted That Met QC Criteria

July 31, 2025

Last Verified

July 1, 2025

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

  • 2024P002124

Plan for Individual participant data (IPD)

Plan to Share Individual Participant Data (IPD)?

YES

IPD Plan Description

Individual Participant Data (IPD) will be shared on a case by case basis with an Institutional data transfer agreement in place.

IPD Sharing Time Frame

12 months after publication.

IPD Sharing 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.

IPD Sharing Supporting Information Type

  • STUDY_PROTOCOL
  • ICF
  • CSR

Drug and device information, study documents

Studies a U.S. FDA-regulated drug product

No

Studies a U.S. FDA-regulated device product

No

product manufactured in and exported from the U.S.

No

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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