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

Gastro Esophageal Reflux Clinical Trial

— AREA21  

Official title:

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)

Clinical Trial Details — Status: Recruiting

Administrative data

• NCT number: NCT05570448
• Other study ID #: PS0100
• Secondary ID: 1650419
• Status: Recruiting
• Phase: N/A
• Start date: February 15, 2022
• Est. completion date: April 2025

Study information

• Verified date: October 2022
• Source: Midwest Veterans' Biomedical Research Foundation
• Contact: April Higbee, BSN
• Phone: 816-861-4700
• Email: april.higbee[@]va.gov
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

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.

Recruitment information / eligibility

• Status: Recruiting
• Enrollment: 36
• Est. completion date: April 2025
• Est. primary completion date: February 2025
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years to 80 Years

Eligibility

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.

Related Conditions & MeSH terms

• Gastro Esophageal Reflux
• Gastroesophageal Reflux

Intervention

Procedure:
• ARAT
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.
• Sham intervention (control)
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.

Locations

Country	Name	City	State
United States	Kansas City VA Hospital	Kansas City	Missouri

Sponsors (1)

Lead Sponsor	Collaborator
Midwest Veterans' Biomedical Research Foundation

Country where clinical trial is conducted

United States, 

References & Publications (19)

Delshad SD, Almario CV, Chey WD, Spiegel BMR. Prevalence of Gastroesophageal Reflux Disease and Proton Pump Inhibitor-Refractory Symptoms. Gastroenterology. 2020 Apr;158(5):1250-1261.e2. doi: 10.1053/j.gastro.2019.12.014. Epub 2019 Dec 19. — View Citation

Desjardin M, Luc G, Collet D, Zerbib F. 24-hour pH-impedance monitoring on therapy to select patients with refractory reflux symptoms for antireflux surgery. A single center retrospective study. Neurogastroenterol Motil. 2016 Jan;28(1):146-52. doi: 10.1111/nmo.12715. Epub 2015 Nov 3. — View Citation

El-Serag HB, Sweet S, Winchester CC, Dent J. Update on the epidemiology of gastro-oesophageal reflux disease: a systematic review. Gut. 2014 Jun;63(6):871-80. doi: 10.1136/gutjnl-2012-304269. Epub 2013 Jul 13. Review. — View Citation

Fayad L, Oberbach A, Schweitzer M, Askin F, Voltaggio L, Larman T, Enderle M, Hahn H, Khashab MA, Kalloo AN, Kumbhari V. Gastric mucosal devitalization (GMD): translation to a novel endoscopic metabolic therapy. Endosc Int Open. 2019 Dec;7(12):E1640-E1645. doi: 10.1055/a-0957-3067. Epub 2019 Nov 25. — View Citation

Hampel H, Abraham NS, El-Serag HB. Meta-analysis: obesity and the risk for gastroesophageal reflux disease and its complications. Ann Intern Med. 2005 Aug 2;143(3):199-211. — View Citation

Hernández Mondragón OV, Zamarripa Mottú RA, García Contreras LF, Gutiérrez Aguilar RA, Solórzano Pineda OM, Blanco Velasco G, Murcio Perez E. Clinical feasibility of a new antireflux ablation therapy on gastroesophageal reflux disease (with video). Gastrointest Endosc. 2020 Dec;92(6):1190-1201. doi: 10.1016/j.gie.2020.04.046. Epub 2020 Apr 25. — View Citation

Hillman L, Yadlapati R, Whitsett M, Thuluvath AJ, Berendsen MA, Pandolfino JE. Review of antireflux procedures for proton pump inhibitor nonresponsive gastroesophageal reflux disease. Dis Esophagus. 2017 Sep 1;30(9):1-14. doi: 10.1093/dote/dox054. Review. — View Citation

Inoue H, Ito H, Ikeda H, Sato C, Sato H, Phalanusitthepha C, Hayee B, Eleftheriadis N, Kudo SE. Anti-reflux mucosectomy for gastroesophageal reflux disease in the absence of hiatus hernia: a pilot study. Ann Gastroenterol. 2014;27(4):346-351. — View Citation

Inoue H, Tanabe M, de Santiago ER, Abad MRA, Shimamura Y, Fujiyoshi Y, Ueno A, Sumi K, Tomida H, Iwaya Y, Ikeda H, Onimaru M. Anti-reflux mucosal ablation (ARMA) as a new treatment for gastroesophageal reflux refractory to proton pump inhibitors: a pilot study. Endosc Int Open. 2020 Feb;8(2):E133-E138. doi: 10.1055/a-1031-9436. Epub 2020 Jan 22. — View Citation

Locke GR 3rd, Talley NJ, Fett SL, Zinsmeister AR, Melton LJ 3rd. Prevalence and clinical spectrum of gastroesophageal reflux: a population-based study in Olmsted County, Minnesota. Gastroenterology. 1997 May;112(5):1448-56. — View Citation

Manner H, Neugebauer A, Scharpf M, Braun K, May A, Ell C, Fend F, Enderle MD. The tissue effect of argon-plasma coagulation with prior submucosal injection (Hybrid-APC) versus standard APC: A randomized ex-vivo study. United European Gastroenterol J. 2014 Oct;2(5):383-90. doi: 10.1177/2050640614544315. — View Citation

Maret-Ouda J, Wahlin K, El-Serag HB, Lagergren J. Association Between Laparoscopic Antireflux Surgery and Recurrence of Gastroesophageal Reflux. JAMA. 2017 Sep 12;318(10):939-946. doi: 10.1001/jama.2017.10981. — View Citation

Peerally MF, Bhandari P, Ragunath K, Barr H, Stokes C, Haidry R, Lovat L, Smart H, Harrison R, Smith K, Morris T, de Caestecker JS. Radiofrequency ablation compared with argon plasma coagulation after endoscopic resection of high-grade dysplasia or stage T1 adenocarcinoma in Barrett's esophagus: a randomized pilot study (BRIDE). Gastrointest Endosc. 2019 Apr;89(4):680-689. doi: 10.1016/j.gie.2018.07.031. Epub 2018 Aug 1. — View Citation

Sami SS, Al-Araji SA, Ragunath K. Review article: gastrointestinal angiodysplasia - pathogenesis, diagnosis and management. Aliment Pharmacol Ther. 2014 Jan;39(1):15-34. doi: 10.1111/apt.12527. Epub 2013 Oct 20. Review. — View Citation

Taïeb S, Rolachon A, Cenni JC, Nancey S, Bonvoisin S, Descos L, Fournet J, Gérard JP, Flourié B. Effective use of argon plasma coagulation in the treatment of severe radiation proctitis. Dis Colon Rectum. 2001 Dec;44(12):1766-71. — View Citation

Vaezi MF, Yang YX, Howden CW. Complications of Proton Pump Inhibitor Therapy. Gastroenterology. 2017 Jul;153(1):35-48. doi: 10.1053/j.gastro.2017.04.047. Epub 2017 May 19. Review. — View Citation

Vakil N, van Zanten SV, Kahrilas P, Dent J, Jones R; Global Consensus Group. The Montreal definition and classification of gastroesophageal reflux disease: a global evidence-based consensus. Am J Gastroenterol. 2006 Aug;101(8):1900-20; quiz 1943. — View Citation

Witteman BP, Conchillo JM, Rinsma NF, Betzel B, Peeters A, Koek GH, Stassen LP, Bouvy ND. Randomized controlled trial of transoral incisionless fundoplication vs. proton pump inhibitors for treatment of gastroesophageal reflux disease. Am J Gastroenterol. 2015 Apr;110(4):531-42. doi: 10.1038/ajg.2015.28. Epub 2015 Mar 31. — View Citation

Yadlapati R, Vaezi MF, Vela MF, Spechler SJ, Shaheen NJ, Richter J, Lacy BE, Katzka D, Katz PO, Kahrilas PJ, Gyawali PC, Gerson L, Fass R, Castell DO, Craft J, Hillman L, Pandolfino JE. Management options for patients with GERD and persistent symptoms on proton pump inhibitors: recommendations from an expert panel. Am J Gastroenterol. 2018 Jul;113(7):980-986. doi: 10.1038/s41395-018-0045-4. Epub 2018 Apr 24. — View Citation

* Note: There are 19 references in all — Click here to view all references

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	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	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
Secondary	Change in Proton pump inhibitor (PPI) use	Frequency of PPI medication use	At 3, 6 and 12 months
Secondary	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
Secondary	Adverse events	Frequency of any adverse event including chest pain, bleeding, dysphagia, hospitalization	Post-randomization (Day 1, Day 30, 3rd, 6th and 12th month)
Secondary	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
Secondary	Esophagitis incidence	LA grade esophagitis at the time of endoscopy	At 3 and 12 months

External Links

•   , Kalapala R, Nabi Z, et al. Anti-Reflux Mucosal Ablation (ARMA) For Refractory Gastroesophageal Reflux Disease - An Interim Analysis, 2021.