Feasibility Study for Evaluating the Effect of Electrical Stimulation on Lower Esophageal Sphincter Pressure and Esophageal Acid Exposure in Patients With Gastroesophageal Reflux Disease

A Feasibility Study: An Evaluation 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 Stimulation System is an investigational device intended to improve the lower esophageal sphincter (LES) resting tone and restore LES function in individuals suffering with gastroesophageal reflux disease (GERD).

Study Overview

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

Detailed Description

EndoStim is developing an investigational medical device specifically designed to deliver electrical stimulation to the LES and has completed two clinical feasibility studies using the EndoStim stimulation system in fifteen subjects.

Acute electrical stimulation resulted in significant LES pressure with no adverse effects reported.

Results of these studies are promising and warrant additional clinical study to evaluate the effectiveness of EndoStim stimulation system to treat GERD over time.

In this study, EndoStim proposes using a fully implantable system. Results of this study are expected to provide confirmation of safety of long-term LES stimulation and may provide long term clinical benefit for GERD patients.

• Study Type: Interventional
• Enrollment (Actual): 24
• Phase: Phase 2

Contacts and Locations

Study Locations

• Chile
  • Santiago, Chile
    • INDISA Clínica da Familia

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 21 years to 65 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

• Subject is between 21 - 65 years of age.
• Subject has a history of heartburn, regurgitation or both for > 6 months prompting physician recommendation of continual daily use of PPI before study entry.
• Baseline GERD-HRQL heartburn score of ≥ 20 off PPI assessed during the run-in phase.
• Subject has an American Society of Anesthesiologists (ASA) Physical Status Classification I or II (or comparable local classification if any).
• Subject has demonstrated satisfactory symptomatic response to a previous course of GERD therapy (≥ 2 weeks); GERD HRQL heartburn score improvement of ≥ 10 on therapy as assessed during the run in phase.
• Subject has exhibited excessive lower esophageal acid exposure during 24-hour pH-metry off antisecretory therapy performed within 6 months of enrollment; pH < 4 for > 5% of total or > 3% of supine 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 > 70% of swallows and > 50% peristaltic contractions on high resolution manometry.
• Subject has signed the informed consent form.

Exclusion Criteria:

• Subject has non-GERD esophageal motility disorders.
• Subject has gastroparesis.
• Subject has significant multisystem diseases.
• Subject has scleroderma requiring therapy in the preceding 2 years .
• Subject has dermatomyositis requiring therapy in the preceding 2 years.
• Subject has Calcinosis-Raynaud's-esophaguschlerodactyly syndrome requiring therapy in the preceding 2 years.
• Subject has Sjogren's Syndrome requiring therapy in the preceding 2 years.
• Subject has Sharp's Syndrome requiring therapy in the preceding 2 years.
• Subject has persistent esophagitis greater than LA grade C.
• Subject has Barrett's epithelium (> M2; >C1) or any dysplasia.
• Subject has a hiatus hernia larger than 3 cm.
• Subject has a body mass Index 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 an autoimmune disorder requiring therapy in the preceding 2 years.
• Subject has 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).
• Subject requires chronic anticoagulant therapy.
• Subject has dysphagia or esophageal peptic structure, excluding Schatzki's ring.
• Subject is pregnant or intends to become pregnant during the trial period.
• Subject is currently enrolled in other potentially confounding research.
• Subject has any condition that, at the discretion of the investigator, would preclude participation in the trial.
• History of any malignancy in the last 2 years
• History of previous esophageal or gastric surgery, including nissen fundoplication

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
Other: Single Arm open label; 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.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Primary Safety Endpoint	Safety will be assessed by incidence and severity of adverse events through 12-week (3 month) follow-up. Included in this assessment will be the proportion of subjects with any of the following outcomes between device implant and completion of the Week 12 evaluation: (1) death, or (2) medical morbidity, including myocardial infarction, pneumonia, wound infection, or perforation requiring hospitalization.	3 months
Primary Endpoint: Functionality	Functionality of the EndoStim system will be assessed by the ability of the device to initiate stimulation as programmed and to accurately detect the patient's posture. Indication of device detection when the patient is lying horizontally and when standing up will be recorded.	Up to 3 months

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
GERD-HRQL	Improvement in GERD-HRQL with LES stimulation at the 12-weeks (3 months) follow-up compared to baseline	3 months
GERD Symptoms	Changes in GERD symptoms as measured by the patient daily symptom-diary as well as the impact of GERD symptoms on quality of life as measured by SF-12 will be compared between baseline assessments and post-implant measures at 12 weeks (3 months).	3 months
Lower Esophageal Measures	The baseline LES end expiratory pressure and the on-stimulation LES end expiratory pressure at 3 months	3 months
Esophageal Acid Exposure	Total fractional esophageal acid exposure time with pH < 4.0. The data on baseline esophageal acid exposure off-therapy, prior to surgical implant of the stimulator and on-stimulation at 12 weeks (3 months) post-implant	3 months

Collaborators and Investigators

• Sponsor: EndoStim Inc.
• Investigators: Principal Investigator: Leonardo RODRIGUEZ, M.D, INDISA Clínica da Familia, Santiago, Chile

Publications and helpful links

General Publications

• Rodriguez L, Rodriguez P, Gomez B, Ayala JC, Oxenberg D, Perez-Castilla A, Netto MG, Soffer E, Boscardin WJ, Crowell MD. Two-year results of intermittent electrical stimulation of the lower esophageal sphincter treatment of gastroesophageal reflux disease. Surgery. 2015 Mar;157(3):556-67. doi: 10.1016/j.surg.2014.10.012. Epub 2014 Nov 6.

Study record dates

Study Major Dates

• Study Start: September 1, 2010
• Primary Completion (Actual): May 1, 2013
• Study Completion (Actual): May 1, 2013

Study Registration Dates

• First Submitted: April 11, 2012
• First Submitted That Met QC Criteria: April 15, 2012
• First Posted (Estimate): April 17, 2012

Study Record Updates

• Last Update Posted (Estimate): February 12, 2014
• Last Update Submitted That Met QC Criteria: February 11, 2014
• Last Verified: January 1, 2013

More Information

Terms related to this study

• Keywords: GERD; Electrical Stimulation; LES Pressure
• Additional Relevant MeSH Terms: Digestive System Diseases; Gastrointestinal Diseases; Stomach Diseases; Gastroenteritis; Intestinal Diseases; Esophageal Motility Disorders; Deglutition Disorders; Esophageal Diseases; Esophagitis; Peptic Ulcer; Duodenal Diseases; Gastroesophageal Reflux; Esophagitis, Peptic
• Other Study ID Numbers: CS004