Clinical trial NCT06529159: H. Pylori Eradication With Argon Plasma During Endoscopy
Official title: H. Pylori Eradication With Argon Plasma During Endoscopy (HEAPE)
Study type: INTERVENTIONAL
Overall status: RECRUITING
Phase: NA
Conditions: Helicobacter Pylori Infection
Helicobacter Pylori
Helicobacter Pylori Gastrointestinal Tract Infection
H. Pylori Infection
H. Pylori Gastrointestinal Disease
Keywords: Urea Breath Test
Argon Plasma Coagulation (APC)
Endoscopy
Plasma Activated Liquid (PAL)
Plasma Medicine
Lead sponsor: Brigham and Women's Hospital
Sponsor class: OTHER
Collaborators: name: Erbe Elektromedizin GmbH
First posted: 2024-07-31
Enrollment: 20
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Intervention model description: Two-arm, randomized, pilot, single-center, prospective clinical study
Primary purpose: TREATMENT

Brief summary: The objective of the study is to investigate the efficacy and safety of an argon plasma-based therapy - HEAPE - in treating H. pylori infections during endoscopic procedures. By filling the stomach with sodium chloride solution that is treated with APC (PAL), the Investigators hypothesize a significant reduction in H. pylori. The use of PAL instead of direct application of APC allows for a broader and more homogeneous application throughout the stomach and a faster procedure time, as the fluid bypasses the thermal effects typically associated with higher electrical power settings and focuses on the bactericidal action of PAL. It is a procedure that does not involve thermal ablation of the stomach lining. Thus, side effects should be expected to be as low as possible.

Two different PAL generation modalities will be compared in this study:

1. HEAPE direct: This modality is the direct generation of PAL in the stomach. The stomach is filled with sodium chloride solution which is then treated with APC. With HEAPE direct a potential decrease of reactive species is avoided, as the treatment happens directly at the intended location in the H. pylori infected stomach.
2. Pre-HEAPE: This modality features the treatment of sodium chloride with APC outside of the patient in a sterile container. After the APC treatment, the generated PAL is administered into the stomach with a syringe through the working channel of the endoscope. Pre-HEAPE allows an easier handling of the APC probe as the treatment of the sodium chloride solution can be done without an endoscope.

To evaluate the immediate effect of this novel treatment approach the metabolic activity of H. pylori will be assessed using a urea breath test (UBT) before and after treatment. A reduction in H. pylori levels can be detected by a reduction in urease activity in the breath test.

After the HEAPE procedure, patients are treated with antibiotics (best practice) as they would be under normal circumstances. Four weeks after treatment, another UBT is performed to determine if H. pylori has been eradicated or if additional antibiotic treatment is indicated.

This two-arm, randomized, pilot, single-center, prospective clinical study is designed to evaluate the safety, tolerability and proof of concept that PAL has the ability to eradicate or reduce the bacterial load of H. pylori in humans.

Detailed description: Helicobacter pylori (H. pylori) is a prevalent bacterial infection that colonizes the gastric mucosa, affecting approximately 50% of the global population. Classified by the WHO as a class 1 carcinogen in 1994 and further supported by extensive evidence, H. pylori is recognized as a leading cause of ulcers and a significant risk factor for the development of gastric cancer. Despite a slight decline in the prevalence of H. pylori infection in developed countries, the absolute number of infected individuals in the U.S. remains alarmingly high at approximately 36% of the U.S. population. Gastric cancer, associated with H. pylori infection, continues to be a major health concern worldwide, accounting for over 1.1 million new cases and approximately 770,000 deaths each year. The causal link between H. pylori infection and nearly 90% of gastric cancer cases underscores the critical importance of effective eradication strategies.

Current treatments for H. pylori infection, which typically consist of triple or quadruple therapy combining two or three antibiotics with proton pump inhibitors (PPIs), are successful in approximately 80% of cases. This leaves a significant proportion of cases unresolved. In addition, the emergence of multidrug-resistant H. pylori strains, particularly those resistant to clarithromycin and quinolones, challenges these conventional approaches. The broader issue of increasing antibiotic resistance, leads to a reliance on back-up antibiotics for cases where standard treatments fail. A sharp decline of eradication rates during the last decade, underscores the need for alternative therapeutic strategies. A recent study estimated the total cost of H. pylori treatment failure to be over $5.3 billion in the U.S., primarily due to hospitalizations, medications, and outpatient visits for complications such as peptic ulcer disease and non-cardia gastric cancer. Research into treatments beyond antibiotics is needed to address the growing risk of resistance and to ensure sustainable, effective solutions for H. pylori infection.

The field of plasma medicine, particularly through the use of Argon Plasma Coagulation (APC), offers promising new avenues for addressing this challenge. APC, a technology with over 30 years of clinical safety and efficacy, has been utilized for bleeding management, ablation of cancerous tissues, and precise treatments in sensitive areas. More recently, it has shown good efficacy in the treatment of cervical intraepithelial lesions (CIN) at lower power levels with no visible macroscopic thermal effect. Recent advancements in plasma medicine have highlighted the antibacterial properties of physical plasma. It has demonstrated remarkable efficacy in wound healing by effectively eradicating bacterial infections, including those resistant to antibiotics. The effect of non-thermal plasma treatment is based on the high energy and voltage of the plasma, which generates reactive oxygen and nitrogen species (RONS), an electric field that can cause electroporative effects, and UV light emitted in the plasma.

These effects are present when plasma is applied directly to the site of action, but also when a liquid medium such as sodium chloride solution is used as a buffer substance. This concept of indirect plasma treatment is often referred to as Plasma Activated Liquid (PAL). In proprietary preclinical studies, PAL generated with APC probes using forced APC Effect 8 has been shown to achieve a 5-log reduction in H. pylori (SK225) after 15 minutes incubation. In a multidrug resistant E. coli 4MRGN stain (VC8874), a 6-log reduction was achieved after 15 minutes incubation.

This demonstrates that PAL harnesses the antimicrobial properties of plasma in a non-thermal, liquid-based approach. This innovative approach allows the effects of plasma to be applied to large surface areas, such as the gastric mucosa, offering a potentially effective treatment for H. pylori infection without the drawbacks associated with antibiotic resistance. The established safety record of APC and the common use of liquids as irrigation or injection solutions in endoscopy provide a solid foundation for its potential applications in the treatment of H. pylori infection.

Eligibility criteria: Inclusion Criteria:

1. Subjects must be 18 years or older
2. Confirmed untreated H. pylori infection
3. Able to understand and sign informed consent
4. Available to return for all routine follow-up study visits
5. Patients should have upper endoscopy scheduled according to latest guidelines, e.g., as a part of their diagnostic work-up of HP positive test, regardless of their decision to participate in the study.

Exclusion Criteria:

1. Patients actively undergoing H.pylori eradication therapy treatment with antibiotics or proton pump inhibitors (PPIs) two weeks prior to the HEAPE procedure.
2. Pregnancy or puerperium
3. Severe cardiopulmonary disease or a history of coronary artery disease (including myocardial infarction within the past 6 months, poorly controlled hypertension, required use of NSAIDs)
4. Lactation
5. An inability to provide informed consent
6. Any other condition which the investigator may deem as an impediment to compliance or hinder completion of the proposed study.
7. Hernias / aspiration risk

Primary outcomes:
measure: Reduction in H. pylori load from baseline to 2 hours after treatment using Urea Breath Test
timeFrame: Baseline, 2 hours post-treatment
Secondary outcomes:
measure: Eradication of H. pylori load from 2 hours after treatment to 4 weeks after treatment using Urea Breath Test
timeFrame: 2 hours post-treatment, 4 weeks post-treatment
measure: Comparison of H. pylori eradication rate between HEAPE + standard of care antibiotic treatment vs standard of care treatment (antibiotics) alone (historical data)
timeFrame: 4 weeks
measure: Comparison of reduction in H. pylori load measured by UBT HEAPE vs. Pre-HEAPE treatment arms from baseline to 2 hours post-treatment
timeFrame: Baseline, 2 hours post-treatment
measure: Comparison of H. pylori load measured by UBT HEAPE vs. Pre-HEAPE treatment arms from baseline to 4 weeks post-treatment
timeFrame: Baseline, 4 weeks post-treatment
measure: Change in dyspepsia symptoms from baseline via patient self-report of symptoms
timeFrame: Baseline, 4 weeks
measure: Change in epigastric pain level from baseline via patient self-report of symptoms using the Abdominal Pain Index
timeFrame: Baseline, 4 weeks
measure: Change in quality of life score from baseline using the 12 item Short Form Survey (SF-12)
timeFrame: Baseline, 4 weeks
measure: Adverse Events intra-procedural and post-treatment
timeFrame: Intra-procedure, 2 hours post-treatment, 4 weeks post-treatment
Other outcomes:
Locations:
city: Boston
country: United States
facility: Brigham and Women's Hospital
state: Massachusetts
Study officials:
affiliation: Brigham and Women's Hospital
name: Christopher C Thompson, MD
role: PRINCIPAL_INVESTIGATOR
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