Anti-Reflux Endoscopic TX Using APC (AREA) in GERD Patients: (The AREA Study)

Study Overview
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Brief Summary
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This will be a randomized clinical trial examining the efficacy and safety of ARAT (intervention group) in patients with chronic GERD symptoms (typical symptoms of GERD, i.e. heartburn or acid reflux/regurgitation at least twice a week) for the last 6 months. Patients must have a positive pH test and a negative manometry (no treatment) procedure.

Official Title
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Anti-Reflux Endoscopic Therapy Using Argon Plasma Coagulation (AREA) in Gastroesophageal Reflux Disease (GERD) Patients: A Single Center, Randomized, Sham, Controlled Trial (The AREA Study)

Conditions
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Gastro Esophageal Reflux

Intervention / Treatment
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* Procedure: ARAT
* Procedure: Sham intervention (control)


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Chronic GERD symptoms (at least 1 typical symptom of GERD, i.e. heartburn or acid reflux/regurgitation at least twice a week) for last 6 months Objective evidence of reflux disease (positive ambulatory pH study.) Exclusion Criteria: Patients unable to or unwilling to participate or consent. Age <18 years or >80 years. Allergic or intolerant to PPI medications. Large hiatal hernia > 3 cm and Hill grade IV. Barrett's esophagus. Esophageal stricture with any prior intervention. Major motility disorder. Eosinophilic esophagitis. Gastroparesis documented by abnormal gastric emptying time. Previous fundoplication, myotomy or LINX surgery. Cirrhosis with esophageal and/or gastric varices.

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 80 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: Anti-reflux mucosal ablation (ARAT)<br>ablation in the gastric cardia using hybrid argon plasma coagulation | Procedure: ARAT<br>* For patients randomized to ARAT intervention, the area of cardia, along greater curvature will be cleaned followed by demarcation of a 1-1.5 cm area of non-ablation zone with two vertical lines by use of Pulsed APC (30W, Effect 2) using the H-APC catheter. Next, the area of cardia, on either side will be injected in sequence using a methylene blue (0.5%) and normal saline (0.9%) using the H-APC catheter jet system (Effect 30-70). Next, the mucosa, starting below the z-line and up to 3 cm below will be treated by Pulsed APC 50W-80W till golden-brown discoloration of the ablated tissue in 270-320 degree. For patients randomized to control or sham intervention, upper endoscopy with procedural sedation was performed followed by markings of landmarks followed by gastroscope retroflexion in the gastric cardia with at least 15 minute of examination time. No H-APC or submucosal injection or other intervention will be performed.<br>* Other names: Anti-reflux mucosal ablation;|
| Sham Comparator: No treatment<br>no ablation | Procedure: Sham intervention (control)<br>* Patients randomized to the control arm, will undergo a sham intervention. This will include performing upper endoscopy with procedural sedation followed by markings of landmarks as described. This will be followed by gastroscope retroflexion in the gastric cardia with at least 15 minute of examination time spent in retroflexion to reciprocate the H-APC intervention. No H-APC or submucosal injection or other intervention will be performed during the upper endoscopy with sham intervention. All Patients will also continue their PPI daily for 4 weeks.<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Change in GERD health related quality of life (GERD-HRQL) score | The primary outcome of quality of life will be measured using the validated GERD related quality of life questionnaire (GERD-HRQL). The total score is 50, and a higher score is associated with more severe symptoms. | At 3, 6 and 12 months | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Change in Reflux disease questionnaire (RDQ) score | RDQ scores will be assessed using a validated questionnaire scale. The total score is 40, and a higher score is associated with more severe symptoms. | At 3, 6 and 12 months | 
| Change in Proton pump inhibitor (PPI) use | Frequency of PPI medication use | At 3, 6 and 12 months | 
| Acid exposure time (AET) | Ambulatory acid reflux testing (wireless pH monitoring system) for measurement. Acid exposure time measures amount of time spent in pH <4. A time >4% is considered positive for acid reflux. | At 3 and 12 months | 
| Adverse events | Frequency of any adverse event including chest pain, bleeding, dysphagia, hospitalization | Post-randomization (Day 1, Day 30, 3rd, 6th and 12th month) | 
| Change in Hiatal hernia grading | Hill grade for hiatal hernia assessment during endoscopy. There are 4 grades: I, II, III and IV depending on the appearance of the hiatus on endoscopy. | At 3 and 12 months | 
| Esophagitis incidence | LA grade esophagitis at the time of endoscopy | At 3 and 12 months |