Anti-reflux Mucosal Ablation Therapy Randomized Sham Control Trial for Gastroesophageal Reflux Disease

Study Overview
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Brief Summary
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The goal of this randomized clinical trial is to investigate the efficacy and safety of antireflux mucosal ablation (ARMA) for patients with refractory gastroesophageal reflux disease (GERD). The trial aim to evaluate : Efficacy of ARMA comparing with medical treatment alone (proton pump inhibitor (PPI)), using GERD-Health Related Quality of Life Questionnaire (GERD- HRQL questionnaire), improvement of acid exposure time and DeMeester score Safety and complications of ARMA Participants will be randomly divided into 2 groups. The intervention group will be undergone ARMA, and the control group will be undergone sham endoscopic treatment. The primary endpoint will be symptoms relief (GERD-HRQL decreases > 50%). The secondary endpoint will be dosage adjustment of PPI, complications, improvement of acid exposure time and DeMeester score.

Official Title
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Efficacy and Safety of Endoscopic Anti-reflux Mucosal Ablation Therapy for Gastroesophageal Reflux Disease: a Single Blind Randomized Sham Controlled Trial

Conditions
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Gastroesophageal Reflux Disease

Intervention / Treatment
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* Procedure: Antireflux mucosal ablation
* Procedure: Sham procedure


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Adults aged over 18 years old History of GERD for over 6 months, who had received PPIs for over 6 months but still had symptoms of typical GERD symptoms (GERD-HRQL score of >8, acid reflux sensation or heartburn), and/or other symptoms as lump throat, night cough, acid related chest tightness (without other possible explanation of these symptoms) Acid exposure time > 6% DeMeester score ≥ 14.72 Exclusion Criteria: Pregnancy BMI>=35 Hiatal hernia > 2cm or Flap Valve Hill grade III/IV GERD LA grade C/D or esophageal ulcer Abnormal anatomy of esophagus (esophagectomy, stricture, diverticulum) Barrett's esophagus with dysplasia Esophageal motility disorders History of gastroparesis Cirrhosis Esophageal and gastric varices Previous gastric surgery and anti-reflux procedures History of scleroderma or dermatomyositis Coagulation disorders (Bleeding tendency and coagulopathy) History of oncological disease (not active within 2 years)

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 75 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Double


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Active Comparator: Antireflux mucosal ablation<br>In patients fulfilling the inclusion criteria and being randomized for ARMA, retroflexion endoscopy to visualize the cardia is performed, followed by mucosa markings with straight-fire APC catheter (ERBE Electromedizin, Tübingen, Germany) in forced coagulation mode (VIO300D, ERBE Electromedizin, Tübingen, Germany, 20W). The marking site at 1-cm and 2-cm distal to squamocolumnar junction at anterior-posterior and lesser curvature site, respectively, sparing the greater curvature site of cardia, is done. After marking, mucosal ablation (forced coagulation mode, 1L/min, 80W) is performed at marking site in a hoarse-shoe shape. Adequate ablation depth is defined as reaching the submucosal layer with blackish discolored tissue with carbonization | Procedure: Antireflux mucosal ablation<br>* Patients are instructed to fast for 6 hours pre-procedurally, which are performed under intravenous propofol sedation. Retroflexion endoscopy to visualize the cardia is performed, followed by mucosa markings with straight-fire APC catheter (ERBE Electromedizin, Tübingen, Germany) in forced coagulation mode (VIO300D, ERBE Electromedizin, Tübingen, Germany, 20W). The marking site at 1-cm and 2-cm distal to squamocolumnar junction at anterior-posterior and lesser curvature site, respectively, sparing the greater curvature site of cardia, is done. After marking, mucosal ablation (forced coagulation mode, 1L/min, 80W) is performed at marking site in a hoarse-shoe shape. Adequate ablation depth is defined as reaching the submucosal layer with blackish discolored tissue with carbonization<br>|
| Sham Comparator: Sham procedure<br>In patients fulfilling the inclusion criteria and being randomized for sham procedure, retroflexion endoscopy to visualize the cardia is performed. Using the straight-fire APC catheter to touch the marking sites similar to the treatment group without electrocauterization is performed | Procedure: Sham procedure<br>* Patients are instructed to fast for 6 hours pre-procedurally, which are performed under intravenous propofol sedation. Retroflexion endoscopy to visualize the cardia is performed. Using the straight-fire APC catheter to touch the marking sites similar to the treatment group without electrocauterization is performed.<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Improvement of gastroesophageal reflux disease symptoms | Clinical success is defined as more than 50% improvement of the GERD-HRQL questionnaire at 3 months after the ARMA procedure. The results are from minimal 0 points up to 50 points. The higher the points, the greater the symptoms. | 3 months | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Complication rate | Recording of all complications related to the ARMA procedure | 12 months | 
| PPI dependency | Requirement and dose of PPI at 3, 6 and 12 months after ARMA | 12 months | 
| Changes in acid exposure time | Changes in acid exposure time in 24 pH meter at 3 and 12 months after ARMA | 12 months | 
| Changes in DeMeester score | Changes in DeMeester score in 24 pH meter at 3 and 12 months after ARMA. A DeMeester score of ≤ 14.72 is considered physiological. | 12 months | 
| Changes in lower esophageal sphincter pressure | Changes in lower esophageal sphincter pressure in high resolution manometry at 3 and 12 months after ARMA | 12 months |