Clinical trial NCT06543316: Marginal Ulcer Healing With Low-Thermal Argon Plasma Endoscopic Treatment
Official title: Accelerated Marginal Ulcer Healing With Low-Thermal Argon Plasma Endoscopic Treatment
Study type: INTERVENTIONAL
Overall status: RECRUITING
Phase: NA
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
Lead sponsor: Brigham and Women's Hospital
Sponsor class: OTHER
Collaborators: name: Erbe USA Incorporated
First posted: 2024-08-09
Enrollment: 100
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: CROSSOVER
Intervention model description: Randomized, two-arm, crossover clinical study
Primary purpose: TREATMENT

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.

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).

Eligibility criteria: 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.

Primary outcomes:
measure: Ulcer Healing Success Rate from baseline endoscopy
timeFrame: Baseline, 4 weeks, 8 Weeks
Secondary outcomes:
measure: Comparison of Time to Ulcer Healing between LTP and SOC groups
timeFrame: Baseline, 4 weeks, 8 weeks
measure: Improvement of Tissue Oxygenation at Ulcer Site in LTP treatment group
timeFrame: Baseline, 4 weeks, 8 weeks
measure: Presence of Procedure-Related Adverse Events
timeFrame: Baseline, up to 8 weeks
measure: Clinical Improvement of Gastrointestinal Symptoms
timeFrame: Baseline, 8 Weeks
measure: Change in quality of life score from baseline using the 12 item Short Form Survey (SF-12)
timeFrame: Baseline, 8 Weeks
Other outcomes:
Locations:
city: Boston
country: United States
facility: Brigham and Women's Hospital
state: Massachusetts
Study officials:
affiliation: Brigham and Womens Hospital
name: Christopher C. Thompson, MD, MSc
role: PRINCIPAL_INVESTIGATOR
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