Anti Reflux Mucosal Ablation Therapy in PPI Dependent GERD (APDG)

Anti Reflux Mucosal Ablation Therapy in PPI Dependent GERD: a Prospective Randomized, Single-blinded, Sham-controlled Trial

This is a prospective, randomized, single-blinded, interventional, controlled trial to evaluate the efficacy and safety of endoscopic anti reflux mucosal ablation (ARMA) in PPI dependent gastroesophageal reflux disease (GERD) in comparison to controls with a sham procedure.

Study Overview

• Status: Recruiting
• Conditions: Gastroesophageal Reflux
• Intervention / Treatment: Procedure: Anti reflux mucosal ablation (ARMA); Procedure: Sham procedure

Detailed Description

Patients who fulfill the inclusion criteria and, after informed consent, are willing to participate in this study will be prepared for ARMA. After sedation the patients will be randomized equally into an intervention and control Group. The patients are blinded to the procedure. The Patients in the intervention group receive ARMA using argon plasma coagulation (APC) at the gastroesophageal junction (EGJ) in two semicircular patterns while the control group receives a sham procedure. The approximate duration of the procedure is 30min. After the procedure the patients receive follow up controls at 2, 4, 6 and 12 months. During the first follow up, 2 months after the procedure symptoms are evaluated by questionnaires (GERD- HRQL, FSSG, VAG). Subsequently the PPI- medication is stopped in all patients until the end of the study or worsening of symptoms. During the second follow up 4 months after the initial procedure the symptoms are reevaluated by questionnaires. The patients are then unblinded and are told if they received ARMA or sham procedure. Those patients who received ARMA are examined by esophagogastroduodenoscopy, esophageal manometry and pH metry. Further assessments is performed by questionnaires 6 and 12 months after the initial procedure.

Those patients in the control group are allowed to take part in a crossover to receive the ARMA procedure as well. If they receive ARMA, symptoms are reevaluated 2 months after the procedure by questionnaires, esophagogastroduodenoscopy, esophageal manometry and pH metry. Further controls are performed after 4, 6 and 12 months by questionnaires.

• Study Type: Interventional
• Enrollment (Anticipated): 50
• Phase: Not Applicable

Contacts and Locations

• Study Contact: Name: Mohamed Abdelhafez, MD; Phone Number: 08941409320; Email: Mohamed.Abdelhafez@mri.tum.de
• Study Contact Backup: Name: Rami Abbassi, MD; Phone Number: 08941409349; Email: rami.abbassi@mri.tum.de

Study Locations

• Germany
  • Bayern
    • Munich, Bayern, Germany, 81675
      • Recruiting
      • II Medizinische Klinik am Klinikum rechts der Isar der Technischen Universität München
      • Contact: Rami Abbassi, MD; Phone Number: 08941409349; Email: rami.abbassi@mri.tum.de
      • Contact: Mohamed Abdelhafez, MD; Phone Number: 9320 +49894140; Email: mohamed.abdelhafez@tum.de

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 70 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

• PPI dependent GERD for at least 6 months
• Pathological esophageal acid exposure, defined by DeMeester score >14.7 or acid exposure time (AET) >4.2% in pH metry while off PPI
• Exclusion of primary esophageal motility disorders by manometry
• Upper endoscopy with biopsy (Exclusion of eosinophilic esophagitis)

Exclusion Criteria:

• Sliding hiatal hernia >3cm
• Los Angeles grade C/D esophagitis
• Primary esophageal motility disorders
• Grade IV Hill´s flap valve
• Pregnancy or planed pregnancy in the next 12 months
• Eosinophilic esophagitis
• Paraesophageal hernia
• Previous esophageal or gastric surgery
• Barretts esophagus
• Liver cirrhosis
• Varices
• Lack of consent
• ASA physical status >III

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Crossover Assignment
• Masking: Single

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Active Comparator: Anti reflux mucosal ablation (ARMA); Patients randomized into the intervention arm receive ARMA and a follow up control after 2, 4, 6 and 12 months. PPI treatment is stopped after 2 months until the end of the study or worsening of symptoms. Esophagogastroduodenoscopy, manometry and pH metry is performed after 4 months.	Procedure: Anti reflux mucosal ablation (ARMA); In patients fulfilling the inclusion criteria and being randomized for ARMA, the procedure using argon plasma coagulation involves two semicircular ablations of the mucosa of the EGJ in a butterfly shape of a width of 2 cm. The approximate duration of the procedure is 30min. Follow includes objective evaluation of reflux disease by reflux questionnaires, esophagogastroduodenoscopy, esophageal manometry, pH metry.
Sham Comparator: Sham procedure; Patients randomized into the sham procedure arm receive a esophagogastroduodenoscopy in the same setting as if ARMA would be performed. Patients in the Control group receive follow up controls after 2 and 4 months and after unblinding after 4 months are allowed to perform a crossover to receive ARMA. PPI treatment is stopped 2 months after the initial sham procedure until the end of the study or worsening of symptoms. If the patients receive ARMA as a crossover reevaluation is performed 2, 4, 6 and 12 months after the actual ARMA procedure.	Procedure: Sham procedure; In patients fulfilling the inclusion criteria and being randomized for sham procedure, the procedure involves esophagogastroduodenoscopy with the same set of movements and duration as the ARMA procedure without the actual ablation.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Improvement in symptoms of gastro esophageal reflux disease	Improvement in symptoms of gastro esophageal reflux disease by more than 50% from baseline in GERD-Health Related Quality of Life Questionnaire (GERD- HRQL) at 4 months after procedure. Total score 0-50; higher scores indicate greater complaints.	4 months

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Change in symptoms of gastro esophageal reflux disease	Change in symptoms of gastro esophageal reflux disease in GERD-Health Related Quality of Life Questionnaire (GERD- HRQL) at 6 and 12 months. Total score 0-50; higher scores indicate greater complaints.	12 months
Change in symptoms of gastro esophageal reflux disease	Change in symptoms of gastro esophageal reflux disease in regurgitation score at 4, 6 and 12 months. Total score 0-30; higher scores indicate greater complaints.	12 months
Change in symptoms of gastro esophageal reflux disease	Change in symptoms of gastro esophageal reflux disease in Frequency scale for the symptoms of GERD (FSSG) at 4, 6 and 12 months. Total score 0-48; higher scores indicate greater complaints.	12 months
Change in symptoms of gastro esophageal reflux disease	Change in symptoms of gastro esophageal reflux disease in visual analog scale (VAS) at 4, 6 and 12 months. Total score 0-10; higher scores indicate greater complaints.	12 months
Complication rate	Recording of all complications in relation to the ARMA- procedure	12 months
PPI dependency	Requirement and dose of PPI at 4, 6 and 12 months	12 months
Change in esophageal acid exposure at 4 months after ARMA	Change in esophageal acid exposure in pH metry 4 months after ARMA	4 months after ARMA
Change in lower esophageal sphincter pressure 4 months after ARMA	Change in lower esophageal sphincter pressure in manometry 4 months after ARMA	4 months after ARMA
Postinterventional pain	Recording of postinterventional pain in visual analog scale (VAS). Higher scores indicate greater complaints.	1day
Changes in cardia morphology	Changes in Hill's flap grade	4 months after ARMA
Technical success rate	Successful completion of ARMA	1 day

Collaborators and Investigators

• Sponsor: Technical University of Munich
• Investigators: Principal Investigator: Mohamed Abdelhafez, MD, Universitiy Hospital Rechts der Isar, Technical Universitiy Munich

Study record dates

Study Major Dates

• Study Start (Anticipated): March 1, 2023
• Primary Completion (Anticipated): January 1, 2025
• Study Completion (Anticipated): March 1, 2025

Study Registration Dates

• First Submitted: February 9, 2023
• First Submitted That Met QC Criteria: March 8, 2023
• First Posted (Estimate): March 10, 2023

Study Record Updates

• Last Update Posted (Estimate): March 10, 2023
• Last Update Submitted That Met QC Criteria: March 8, 2023
• Last Verified: March 1, 2023

More Information

Terms related to this study

• Keywords: anti reflux mucosal ablation; ARMA
• Additional Relevant MeSH Terms: Digestive System Diseases; Gastrointestinal Diseases; Esophageal Motility Disorders; Deglutition Disorders; Esophageal Diseases; Gastroesophageal Reflux
• Other Study ID Numbers: R0001

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No