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

NCT01574339 | Completed DMC

• 1 other identifier: CS005
• Study Type: interventional
• Target: 42
• Locations: 8 countries
• Sites: 10

Brief Summary

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).

Conditions

Gastroesophageal Reflux Disease

Keywords

GERD; LES Pressure; Electrical Stimulation

Outcome Measures

Primary Outcomes (1)

• 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 Outcomes (11)

• Change in GERD-HRQL

  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 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

  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

  Baseline LES end expiratory pressure (LESPpre) will be compared with the end expiratory pressure (LESPpost) at 3 and 6 months.

• Change in GI symptoms

  Symptoms will be compared between baseline (as measured while on and off PPI) to 1, 3, 6, 12, 18 and 24 months.

Study Arms (1)

Treatment Arm

EXPERIMENTAL

EndoStim LES Stimulation System

Device: EndoStim LES Stimulation System

Interventions

EndoStim LES Stimulation System DEVICE

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.

Treatment Arm

Eligibility Criteria

• Age: 21 Years - 70 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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.

You may not qualify if:

• 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.

Sponsors & Collaborators

• EndoStim Inc.: lead

Study Sites (10)

Hospital Clinico de la Pontificia Universidad Catolica de Chile

Santiago, Chile

Location

San Ignacio

Bogotá, Colombia

Location

Chinese University of Hong Kong (CUHK) / Prince of Whales

Hong Kong, Hong Kong

Location

Asian Institute of Gastroenterology

Hyderabad, 500082, India

Location

. Zalvador Zubiran National Institute of Medical Science and Nutrition

Mexico City, Mexico

Location

AMC Amsterdam

Amsterdam, 1105, Netherlands

Location

UMC Maastrcht

Maastricht, Netherlands

Location

UMC Utrecht

Utrecht, 3508, Netherlands

Location

North Shore Hospital

Auckland, Takapuna, New Zealand

Location

St. Thomas Hospital

London, United Kingdom

Location

Related Publications (3)

• 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.

  PMID: 18286675 BACKGROUND

• 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.

  PMID: 18687754 BACKGROUND

• 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.

  PMID: 26153531 DERIVED

MeSH Terms

Conditions

Gastroesophageal Reflux

Condition Hierarchy (Ancestors)

Esophageal Motility Disorders; Deglutition Disorders; Esophageal Diseases; Gastrointestinal Diseases; Digestive System Diseases

Study Officials

• 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

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: not applicable
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Model Details: All enrolled subjects will receive a functioning device and have stimulation delivered throughout the study.

Study Record Dates

• First Submitted: March 22, 2012
• First Posted: April 10, 2012
• Study Start: August 1, 2011
• Primary Completion: December 1, 2016
• Study Completion: December 1, 2016
• Last Updated: February 14, 2025

Record last verified: 2025-02

Data Sharing

• IPD Sharing: Will not share

Locations

IN (1); CO (1); GB (1); HK (1); CL (1); ME (1); NZ (1); NL (3)