Effect of Long-Term Electrical Stimulation on LES Pressure and Esophageal Acid Exposure in Patients With GERD

An Investigation of the Effect of Long-Term Electrical Stimulation on Lower Esophageal Sphincter (LES) Pressure and Esophageal Acid Exposure in Patients With Gastroesophageal Reflux Disease (GERD)

The EndoStim LES Stimulation System is an investigational device intended to improve the LES pressure and restore Lower Esophageal Sphincter (LES) function in individuals suffering from Gastroesophageal Reflux Disease (GERD).

Study Overview

• Status: Completed
• Conditions: Gastroesophageal Reflux Disease
• Intervention / Treatment: Device: EndoStim LES Stimulation System

Detailed Description

EndoStim has developed an investigational medical device specifically designed to deliver electrical stimulation to the LES and has completed two clinical feasibility studies using an external version of the EndoStim stimulation system in fifteen subjects. In these two short-term studies, electrical stimulation resulted in significant increases in LES pressure.

This study will further evaluate the safety of the procedure and its feasibility for use in this group of patients.

• Study Type: Interventional
• Enrollment (Actual): 42
• Phase: Not Applicable

Contacts and Locations

Study Locations

• Chile
  • Santiago, Chile
    • Hospital Clinico de la Pontificia Universidad Catolica de Chile
• Colombia
  • Bogota, Colombia
    • San Ignacio
• Hong Kong
  • Hong Kong, Hong Kong
    • Chinese University of Hong Kong (CUHK) / Prince of Whales
• India
  • Hyderabad, India, 500082
    • Asian Institute Of Gastroenterology
• Mexico
  • Mexico City, Mexico
    • . Zalvador Zubiran National Institute of Medical Science and Nutrition
• Netherlands
  • Amsterdam, Netherlands, 1105
    • AMC Amsterdam
  • Maastricht, Netherlands
    • UMC Maastrcht
  • Utrecht, Netherlands, 3508
    • UMC Utrecht
• New Zealand
  • Takapuna
    • Auckland, Takapuna, New Zealand
      • North Shore Hospital
• United Kingdom
  • London, United Kingdom
    • St. Thomas Hospital

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 21 years to 70 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No

Description

Inclusion Criteria:

• Subject is between 21 - 70 years of age.
• Subject has a history of heartburn, regurgitation or both for > 12 month prompting physician recommendation of continual daily use of PPI before study entry.
• Baseline GERD HRQL heartburn score following 10-14 days off PPI which is ≥ 20 and at least 10 points higher than the on PPI score
• Subject who are on standard medical therapy for 12 months or longer and experience discomfort or who are otherwise dissatisfied with GERD symptoms
• Subjects with a GERD condition that in the opinion of the PI justifies a minimally invasive reversible procedure prior to attempting anatomical change such as Nissen fundoplication
• Subject has an American Society of Anesthesiologists (ASA) Physical Status Classification I or II (or comparable local classification if any).
• Subject has exhibited excessive lower esophageal acid exposure during 24-hour pHmetry of antisecretory therapy performed within 6 months of screening visit; pH < 4 for > 5% of total time.
• Subject has a resting LES end expiratory pressure > 5mm Hg and < 15 mm Hg on a high resolution manometry within 6 months of enrollment.
• Subject has esophagitis ≤ Grade C (LA classification) on upper endoscopy within 6 months of enrollment.
• Subject has esophageal body contraction amplitude > 30 mmHg for > 50% of swallows and > 50% peristaltic contractions on high resolution manometry.
• Subject has signed the informed consent form and is able to adhere to study visit schedule.

Exclusion Criteria:

• Subject has any non-GERD esophageal motility disorders.
• Subject has gastroparesis.
• Subject has any significant multisystem diseases.
• Subject has an autoimmune or a connective tissue disorder (e.g. scleroderma, dermatomyositis, Calcinosis-Raynaud's-Esophagus, Sclerodactyly Syndrome (CREST), Sjogren's Syndrome, Sharp's Syndrome), requiring therapy in the preceding 2 years.
• Subject has Barrett's epithelium (> M2; > C1) or any grade of dysplasia.
• Subject has a hiatal hernia larger than 3 cm.
• Subject has a body mass index (BMI) greater than 35 kg/m2.
• Subject has Type 1 diabetes mellitus
• Subject has uncontrolled Type 2 diabetes mellitus (T2DM) defined as HbA1c > 9.5 in the previous 6 months, or has T2DM for > 10 years.
• Subject has a history of suspected or confirmed esophageal or gastric cancer.
• Subject has esophageal or gastric varices.
• Subject has significant cardiac arrhythmia or ectopy or significant cardiovascular disease.
• Subject has an existing implanted electrical stimulator (e.g., pacemaker, AICD).
• Subject requires chronic anticoagulant therapy.
• Subject has dysphagia or esophageal peptic stricture, excluding Schatzki's ring.
• Subject of child-bearing potential who is pregnant or intends to become pregnant during the trial period.
• Subject is currently enrolled in other potentially confounding research.
• History of any malignancy in the last 2 years.
• History of previous esophageal or gastric surgery, including nissen fundoplication.
• Subject has any condition that, at the discretion of the investigator or sponsor, would preclude participation in the trial.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: N/A
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

Participant Group / Arm

Intervention / Treatment

Experimental: Treatment Arm; EndoStim LES Stimulation System

Device: EndoStim LES Stimulation System; The EndoStim LES Stimulation System comprises three components: an electrical stimulation lead, an implantable pulse generator (IPG) and an external programmer. The IPG and stimulation lead are to be implanted within the subject's body using conventional laparoscopy. The device programmer is to be used by the study investigator and/or a technical representative.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Incidence and severity of adverse events	Safety will be assessed by incidence and severity of adverse events through 24 months of follow-up.	24 months

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Change in GERD-HRQL	Change from baseline in GERD-HRQL. The full title of this scale is GERD Health-Related Quality of Life (GERD-HRQL) Questionnaire. The scale is as follows, with the worst outcome scored as a 5: 0=No Symptoms; Noticeable, but not bothersome; Noticeable, bothersome, but not every day; Bothersome daily; Bothersome and affects daily activities; Incapacitating to do daily activities	Change in GERD-HRQL and RDQ questionnaire score when available from baseline (as measured off PPI) to 1, 3, 6, 12, 18 and 24 months. Heartburn and regurgitation scores will be calculated separately.
Change in GERD symptoms	Changes in GERD symptoms measured by the SF-12 questionnaire at 6, 12, and 24 months compared to baseline. The full name of the scale is SF-12v2® PRO Health Survey which is a short-form patient-reported outcome (PRO) measurement that captures physical and mental well-being across eight health domains, for a variety of diseases, conditions, and treatment groups. It's made of two main summary scores: the Physical Component Summary (PCS) and the Mental Component Summary (MCS). the practical ranges observed in a large U.S. general population are; PCS: 11.1 to 69.4; MCS: 7.4 to 73.2 Higher scores on both PCS and MCS indicate better health	Changes in GERD symptoms as measured by the SF-12 questionnaire will be compared between baseline assessments and post-implant measures at 6, 12, and 24 months.
Change in GERD symptoms	Change from baseline GERD symptoms measured by patient diary.	Changes in GERD symptoms as measured by the patient daily symptom-diary at 3, 6, 12, 18 and 24 months Vs. baseline.
Change in LES pressure	Change from baseline in LES baseline and expiratory pressure	Baseline LES end expiratory pressure (LESPpre) will be compared with the end expiratory pressure (LESPpost) at 3 and 6 months.
Change in GI symptoms	Change from baseline in GI symptoms (while on and off PPI)	Symptoms will be compared between baseline (as measured while on and off PPI) to 1, 3, 6, 12, 18 and 24 months.
Change in esophageal acid exposure	Change in number of reflux events > 1 minute at baseline compared to 3, 6, 12 and 24 months.	Number of reflux events >1 minute will be compared between baseline and 3, 6, 12 and 24 months.
Change in esophageal acid exposure	Change in number of reflux events > 5 minutes at baseline compared to 3, 6, 12 and 24 months.	Number of reflux events >5 minutes will be compared between baseline and 3, 6, 12 and 24 months.
Change in medication usage	Change from baseline in antisecretory medication use	The use of antisecretory medication will be compared between baseline and 3, 6, 12, 18 and 24 months.
Change in sleep-related quality of life	Change from baseline in Pittsburgh Sleep Quality Index (PSQI) scores. The full name of the scale Pittsburgh Sleep Quality Index (PSQI). It is a self-report questionnaire that assesses sleep quality over a one-month time interval. Each component score of the PSQI ranges from 0 to 3, with 3 indicating the greatest dysfunction or disturbance. The seven component scores are then summed to obtain a global PSQI score, which ranges from 0 to 21. Higher scores indicate poorer sleep quality, with a score greater than 5 suggesting significant sleep difficulties.	Baseline and 6, 12, and 24 months scores of Sleep quality questionnaire.
Change in work productivity	Change from baseline in Work Productivity and Activity Impairment Questionnaire scores. The Work Productivity and Activity Impairment (WPAI) Questionnaire is a 6-item instrument designed to measure impairments in work and activities over the past 7 days. It assesses four main domains: Absenteeism (work time missed); Presenteeism (impairment at work / reduced on-the-job effectiveness); Work productivity loss (overall work impairment / absenteeism plus presenteeism); Activity impairment It produces scores for each domain expressed as impairment percentages, with higher numbers indicating greater impairment and less productivity	Baseline and 6, 12, and 24 months scores of Sleep quality and Work productivity questionnaires
Change in esophageal acid exposure	Change in percent 24-hour esophageal pH <4.0 at baseline compared to value at 3, 6, 12 and 24 months.	pH will be compared between baseline and 3, 6, 12 and 24 months.

Collaborators and Investigators

• Sponsor: EndoStim Inc.
• Investigators: Principal Investigator: A. J. Bredenoord, Dr. med., Academisch Medisch Centrum - Universiteit van Amsterdam (AMC-UvA); Principal Investigator: T. Horbach, PD. Dr. med., Stadtkrankenhaus Schwabach, Schwabach, Germany; Principal Investigator: A. Escalona, Dr. med., Hospital Clinico de la Pontificia Universidad Catolica de Chile, Santiago, Chile; Principal Investigator: Nageshwar Reddy, M.D.,, Asian Institute Of Gastroenterology

Publications and helpful links

General Publications

• Kappelle WF, Bredenoord AJ, Conchillo JM, Ruurda JP, Bouvy ND, van Berge Henegouwen MI, Chiu PW, Booth M, Hani A, Reddy DN, Bogte A, Smout AJ, Wu JC, Escalona A, Valdovinos MA, Torres-Villalobos G, Siersema PD. Electrical stimulation therapy of the lower oesophageal sphincter for refractory gastro-oesophageal reflux disease - interim results of an international multicentre trial. Aliment Pharmacol Ther. 2015 Sep;42(5):614-25. doi: 10.1111/apt.13306. Epub 2015 Jul 8.
• Sidhu AS, Triadafilopoulos G. Neuro-regulation of lower esophageal sphincter function as treatment for gastroesophageal reflux disease. World J Gastroenterol. 2008 Feb 21;14(7):985-90. doi: 10.3748/wjg.14.985.
• Sanmiguel CP, Hagiike M, Mintchev MP, Cruz RD, Phillips EH, Cunneen SA, Conklin JL, Soffer EE. Effect of electrical stimulation of the LES on LES pressure in a canine model. Am J Physiol Gastrointest Liver Physiol. 2008 Aug;295(2):G389-94. doi: 10.1152/ajpgi.90201.2008.

Study record dates

Study Major Dates

• Study Start: August 1, 2011
• Primary Completion (Actual): December 1, 2016
• Study Completion (Actual): December 1, 2016

Study Registration Dates

• First Submitted: March 22, 2012
• First Submitted That Met QC Criteria: April 8, 2012
• First Posted (Estimated): April 10, 2012

Study Record Updates

• Last Update Posted (Actual): March 25, 2025
• Last Update Submitted That Met QC Criteria: February 12, 2025
• Last Verified: February 1, 2025

More Information

Terms related to this study

• Keywords: GERD; Electrical Stimulation; LES Pressure
• Additional Relevant MeSH Terms: Digestive System Diseases; Gastrointestinal Diseases; Esophageal Diseases; Esophageal Motility Disorders; Deglutition Disorders; Gastroesophageal Reflux
• Other Study ID Numbers: CS005

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
• product manufactured in and exported from the U.S.: No