Electrical Stimulation Therapy (EST) of the Lower Esophageal Sphincter (GERD) (EST-SHAM-EUR)

Electrical Stimulation Therapy (EST) of the Lower Esophageal Sphincter: a Multicenter, Randomized, Double-blind, Sham-controlled Parallel-group Trial Evaluating Short Term Efficacy of EndoStim Device on GERD

The investigational device that will be used in this trial is the EndoStim® Lower Esophageal Sphincter (LES) Stimulation System.

The purpose of this trial is to evaluate the safety and the effectiveness of electrical stimulation therapy (EST) on the lower esophageal sphincter (LES) in the treatment of subjects with gastroesophageal reflux disease (GERD).

The study population will consist of subjects diagnosed with pathological GERD as defined by abnormal pH and who complain of heartburn, regurgitation or both for > 6 months, on a daily PPI use.

Study Overview

• Status: Terminated
• Conditions: GERD
• Intervention / Treatment: Procedure: Laparoscopic IPG and lead implant procedure; Device: Active Electric Stimulation Therapy; Device: Delayed Electric Stimulation Therapy

Detailed Description

Study Design:

Multicenter, randomized, double-blind, sham-controlled study. All subjects undergo screening and baseline visits, followed by system implantation, and randomization after 2 weeks to either a treatment Group (stimulation) or Control Group (delayed stimulation).

Randomized subjects complete a 10-week, double-blind phase. At the 14-week visit, subjects are unblinded, control group subjects begin receiving stimulation, and all subjects are followed for an additional 9-month open-label treatment phase.

Subjects continue receiving stimulation for an extended follow-up phase involving annual visits through 5 years.

Study Visits:

Screening and baseline visits. Laparoscopic implantable pulse generator (IPG) and lead implant procedure. Post-implant follow-up office visits at 2 weeks/randomization, 6, 10, 14, 24 and 48 weeks, followed by annual visits through 5 years.

Sample Size and Scope:

Forty-six subjects will be implanted and followed to 12 months after stimulation treatment at 3 investigational sites.

• Study Type: Interventional
• Enrollment (Actual): 1
• Phase: Not Applicable

Contacts and Locations

Study Locations

• Belgium
  • Brussels, Belgium, 1070
    • Gastroenterology Department, Erasme University Hospital
• France
  • Lyon Cedex 3
    • Lyon, Lyon Cedex 3, France, 69437
      • Hôpital Edouard Herriot, Service d'Explorations Fonctionnelles Digestives, Pavillons H et L, 5 Place d'Arsonval

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:

• Subject able and willing to provide written informed consent
• Subject able and willing to comply with required study procedures and follow-up schedule
• Typical symptoms of GERD (regurgitation and/or heartburn) for longer than 6 months, heartburn responding to PPI therapy. Subject may also complain of atypical symptoms of GERD that may persist on PPI
• Daily dose of PPI or other acid neutralization drugs because of PPI intolerance
• Baseline visit GERD-HRQL score ≥ 20 following 14 days off-PPI and at least 10 points higher than their on-PPI (or other acid-neutralization drugs) GERD-HRQL score recorded during the Screening Visit
• Excessive lower esophageal acid exposure during pH monitoring (defined as distal esophageal pH < 4 for > 5.0% of the monitoring time) performed after 14 days off PPIs
• Subject is a suitable surgical candidate able to undergo general anesthesia and laparoscopic surgery.

Exclusion Criteria:

• Previous EndoStim LES System implant and/or implant attempt
• Previous esophageal surgery, including Nissen fundoplication
• Previous endoscopic intervention for the treatment of GERD and/or Barrett's esophagus
• Hiatal hernia larger than 2 cm as determined by any diagnostic investigation (i.e., endoscopy, manometry or laparoscopic visualization)
• Gastroparesis
• Any non-GERD esophageal motility disorders
• Esophageal stricture or significant esophageal anatomic abnormalities
• Barrett's epithelium or any grade of dysplasia
• Documented history of esophagitis Grade C or D (LA Classification)
• History of suspected or confirmed esophageal or gastric cancer
• Esophageal or gastric varices
• Symptoms of dysphagia more than once per week within the last 3 months
• Suspected or known allergies to titanium, platinum, iridium, stainless steel, silicone, epoxy, or nylon
• Body mass index (BMI) > 35 kg/m2
• Any significant multisystem diseases
• Autoimmune or a connective tissue disorder (scleroderma, dermatomyositis, Calcinosis-Raynaud's-Esophagus Sclerodactyly Syndrome (CREST), Sjogren's Syndrome, Sharp's Syndrome, etc.) requiring therapy in the preceding 2 years
• Type 1 diabetes mellitus or uncontrolled Type 2 diabetes mellitus (T2DM) defined as HbA1c > 9.5 in the previous 6 months or at screening/baseline, or has T2DM for > 10 years
• Significant cardiac arrhythmia or ectopy or significant cardiovascular disease (i.e. unstable angina pectoris, hemodynamically significant valvular disease, severe congestive heart failure), or cardiac therapeutic intervention within the last 6 months.
• Significant cerebrovascular event within the last 6 months
• Existing implanted electrical stimulator (pacemaker, implantable cardioverter defibrillator, deep brain stimulator (DBS), bone growth or pelvic floor stimulators, drug pumps, etc.)
• Chronic anticoagulant therapy
• Female subject of child-bearing potential and is pregnant or nursing, or intends to become pregnant during the trial period, who is not using a reliable form of birth control
• Subject is currently enrolled in other potentially confounding research
• Active infection as determined by the investigator
• History of any malignancy in the last 2 years
• Life expectancy less than 3 years
• Diagnosed major psychiatric disorder (bipolar, schizophrenia, etc.)

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Triple

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Active Comparator: Active Electric Stimulation Therapy; The subject receives Active Electric Stimulation Therapy for 12 weeks, 2 weeks after laparoscopic IPG and lead implant procedure. The subject and physician will be blinded to the randomization group assignment. The subject continues on stimulation treatment after 14 weeks and an extended open-label follow-up phase includes annual visits through 5 years.	Procedure: Laparoscopic IPG and lead implant procedure; EST placement; Other Names: EndoStim; Device: Active Electric Stimulation Therapy; Device programming by the technician to deliver the EST system active (Treatment group) or no stimulation (Control group) for the following 12 weeks, at the 2 weeks visit.; Other Names: EndoStim
Sham Comparator: Delayed Electric Stimulation Therapy; The subject receives no active Electric Stimulation Therapy for 12 weeks, 2 weeks after laparoscopic IPG and lead implant procedure. The subject and physician will be blinded to the randomization group assignment. The subject will receive Active Electric Stimulation Therapy at week 14 visit, and an extended open-label follow-up phase includes annual visits through 5 years.	Procedure: Laparoscopic IPG and lead implant procedure; EST placement; Other Names: EndoStim; Device: Delayed Electric Stimulation Therapy; Device programming by the technician to deliver the EST system no stimulation for the following 12 weeks at the 2 weeks visit. Active Electric Stimulation Therapy will be programmed at the 14 weeks visit.; Other Names: EndoStim

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Efficacy of EST on GERD symptoms (mean improvement in the GERD- health-related quality of life (HRQL) scores from baseline in control and treatment groups)	Comparison between Treatment and Control Groups of the mean improvement in the composite GERD-HRQL scores from baseline measured after at least 14 days off proton pump inhibitors (PPIs)	14 weeks

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Safety (Rate of occurrence of device- and procedure-related adverse events)		12 months
Number of subjects achieving GERD symptom success	Improvement in the total GERD-HRQL score of 50% or more compared to pre-implantation score off PPI	12 months
Reflux symptoms measured by GERD-HRQL score	Mean improvement in the composite GERD-HRQL scores from baseline measured after at least 14 days off proton pump inhibitors (PPIs)	6 months
Reflux symptoms measured by GERD-HRQL score	Mean improvement in the composite GERD-HRQL scores from baseline measured after at least 14 days off proton pump inhibitors (PPIs)	12 months
Number of subjects able to stop regular use of acid-suppression	Defined as 50% or more days without PPI use	12 months
Number of subjects able to stop all use of acid-suppression medication		12 months
Percentage of asymptomatic patients	Defined as an improvement in their total GERD-HRQL score of 50% or more compared to pre-implantation score off PPI) in treatment and control groups, off-PPI for the last 2 weeks.	14 weeks
Incidence of reflux esophagitis		12 months
Quality of life measured by EQ-5D EuroQol score	Difference in patient's EQ-5D score, compared to pre-implantation score on and off PPI.	14 weeks
Quality of life measured by EQ-5D score	Difference in patient's EQ-5D score, compared to pre-implantation score on and off PPI.	6 months
Quality of life measured by EQ-5D score	Difference in patient's EQ-5D score, compared to pre-implantation score on and off PPI.	12 months
Efficacy of EST on acid reflux measured by esophageal pH	Difference in % 24 hour esophageal pH<4 in Treatment and Control groups (total, upright, supine, postprandial (2h)).	14 weeks
Efficacy of EST on acid reflux measured by DeMeester score	Difference in DeMeester score in Treatment and Control groups.	14 weeks
Percentage of subjects achieving pH success	Defined as normalization (pH < 4 for no more than 4.1% of monitoring time) or > 50% improvement in their distal esophageal acid exposure compared to their baseline off-PPI distal esophageal pH.	14 weeks
Efficacy of EST on reflux episodes measured by esophageal impedance	Difference in the number of reflux episodes (total, upright, supine, postprandial (2h), acidic, weakly acidic, weakly alkaline, and proximal extent (15 cm) in Treatment and Control groups.	14 weeks
Difference in lower esophageal sphincter (LOS) pressure and integrated relaxation pressure at 4 seconds (IRP4s) in Treatment and Control groups		14 weeks
Comparison of GERD-HRQL scores in Treatment and Control groups		14 weeks
Comparison of quality of life measured by EQ-5D in Treatment and Control groups		14 weeks

Collaborators and Investigators

• Sponsor: Erasme University Hospital
• Collaborators: EndoStim Inc.

Study record dates

Study Major Dates

• Study Start: January 1, 2015
• Primary Completion (Actual): November 1, 2015
• Study Completion (Actual): November 1, 2015

Study Registration Dates

• First Submitted: July 24, 2015
• First Submitted That Met QC Criteria: July 30, 2015
• First Posted (Estimate): August 4, 2015

Study Record Updates

• Last Update Posted (Estimate): November 20, 2015
• Last Update Submitted That Met QC Criteria: November 19, 2015
• Last Verified: November 1, 2015

More Information

Terms related to this study

• Keywords: Reflux; Reflux disease; Gastroesophageal reflux disease; Lower esophageal sphincter stimulation
• Additional Relevant MeSH Terms: Digestive System Diseases; Gastrointestinal Diseases; Esophageal Motility Disorders; Deglutition Disorders; Esophageal Diseases; Gastroesophageal Reflux
• Other Study ID Numbers: ESE-001