An Investigation of the EndoStim® Lower Esophageal Sphincter (LES) Stimulation System for the Treatment of Reflux

A Multicenter, Randomized, Double-Blind, Sham-Controlled Clinical Investigation of the EndoStim® Lower Esophageal Sphincter (LES) Stimulation System for the Treatment of Gastroesophageal Reflux Disease (GERD)

The purpose of this investigation is to demonstrate the safety and effectiveness of Lower Esophageal Sphincter (LES) Stimulation System in treating gastroesophageal reflux disease (GERD). This investigation is a multicenter, randomized, double-blind, sham-controlled study. After the implant procedure, subjects will be randomized to either the Treatment Group (immediate stimulation) or Control Group (delayed stimulation) for six months followed by an additional open-label phase in which all subjects will receive electrical stimulation. Subjects continue on stimulation treatment in an extended open-label follow-up phase through 5 years post-stimulation.

Study Overview

• Status: Terminated
• Conditions: Gastroesophageal Reflux; Reflux, Gastroesophageal; Gastroesophageal Reflux Disease (GERD); Acid Reflux
• Intervention / Treatment: Procedure: Laparoscopic implantation surgery; Device: EndoStim stimulation from Month 6 thru end of study; Device: Sham EndoStim stimulation for first six months of study; Device: EndoStim stimulation for first six months of study

Detailed Description

The purpose of this investigation is to demonstrate the safety and effectiveness of the EndoStim® Lower Esophageal Sphincter (LES) Stimulation System in the treatment of subjects with gastroesophageal reflux disease (GERD). This investigation is a multicenter, randomized, double-blind, sham-controlled clinical investigation. After the implant procedure, subjects will be randomized to either the Treatment Group (immediate stimulation) or Control Group (delayed stimulation) for a 6-month, double-blind phase followed by an additional open-label treatment phase in which all subjects will receive electrical stimulation therapy for a total of 12 months. Subjects continue on stimulation treatment and an extended open-label follow-up phase includes an 18 month post-stimulation phone interview followed by annual visits through 5 years post-stimulation.

• Study Type: Interventional
• Enrollment (Actual): 161
• Phase: Not Applicable

Contacts and Locations

Study Locations

• Belgium
  • Leuven, Belgium
    • Universitaire Ziekenhuizen Leuven
• Netherlands
  • Maastricht, Netherlands
    • Clinical Trial Center Maastricht
• United Kingdom
  • London, United Kingdom
    • University College London
• United States
  • Arizona
    • Phoenix, Arizona, United States, 85013
      • St. Joseph's Hospital and Medical Center
    • Scottsdale, Arizona, United States, 85258
      • HonorHealth Research Institute
  • California
    • Los Angeles, California, United States, 90033
      • University of Southern California (USC)
    • Stanford, California, United States, 94305
      • Stanford Center for Clinical Research
  • Colorado
    • Englewood, Colorado, United States, 80113
      • Institute of Esophageal and Reflux Surgery
  • Florida
    • Tampa, Florida, United States, 33606
      • University of South Florida
  • New York
    • New York, New York, United States, 10032
      • Columbia University Medical Center
    • New York, New York, United States, 10021
      • Cornell University Weill Medical College
  • North Carolina
    • Chapel Hill, North Carolina, United States, 27599
      • University of North Carolina
    • Charlotte, North Carolina, United States, 28260
      • Carolinas Healthcare System
  • Ohio
    • Cleveland, Ohio, United States, 44109
      • The MetroHealth System
    • Columbus, Ohio, United States, 43210
      • The Ohio State University Medical Center
  • Oregon
    • Portland, Oregon, United States, 97213
      • Oregon Clinic
    • Portland, Oregon, United States, 97239
      • Oregon Health Science University
  • Pennsylvania
    • Pittsburgh, Pennsylvania, United States, 15224
      • Allegheny Health Network Research Institute
  • Tennessee
    • Nashville, Tennessee, United States, 37212
      • Vanderbilt University Medical Center
  • Texas
    • Round Rock, Texas, United States, 78665
      • Baylor Scott & White Research Institute
  • Virginia
    • Richmond, Virginia, United States, 23298
      • Virginia Commonwealth University

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 22 years to 75 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

1. Able and willing to provide written informed consent
2. Able and willing to comply with required study procedures and follow-up schedule
3. 22 - 75 years of age at the time of informed consent
4. Documented symptoms of gastroesophageal reflux disease (GERD) for longer than 6 months (regurgitation and/or heartburn which is defined as burning epigastric or substernal pain which responds to acid neutralization or suppression) which requires daily use of proton pump inhibitors (PPIs) or other anti-reflux drug therapy, who continue to have symptoms despite maximum medical therapy or are "intolerant" -severe side-effects (e.g. anaphylaxis or severe allergic reaction, recurrent C. difficile, severe hypomagnesaemia) to one PPI or mild/moderate side effect (e.g. nausea, vomiting, diarrhea or abdominal pain) to at least 2 PPIs of different chemical classes.
5. Symptomatic improvement on PPI therapy demonstrated by a composite GERD-health-related quality of life (HRQL) score of ≥20 off PPI, and a ≥10 point improvement on PPI compared to the off PPI composite GERD-HRQL score. Patients who meet the definition above of PPI intolerant are not required to have ≥10 point improvement. The on-PPI score to satisfy this criterion will be the score from the GERD-HRQL assessment completed after resuming PPIs following the Baseline visit.
6. Excessive lower esophageal acid exposure during pH monitoring (defined as distal esophageal pH < 4 for > 6.0% of the monitoring time) performed after at least 5 days off of PPIs and at least 2 days off of H2 blockers. At least 18 hour of esophageal pH recording will be considered adequate and inclusion will be based on the day (at least 18 hours of valid data) with the highest acid exposure percentage time.
7. Esophagitis ≤ Grade B (Los Angeles (LA) classification) as measured by upper endoscopy off PPI and H2 blockers for 10-14 days
8. Esophageal body contraction amplitude > 30 mmHg for > 30% of swallows and > 30% peristaltic contractions on HRM or ≥ 30% peristaltic contractions with DCI >450.
9. Suitable surgical candidate able to undergo general anesthesia and laparoscopic surgery

Exclusion Criteria:

1. Previous EndoStim LES System implant and/or implant attempt
2. Previous surgery involving the gastroesophageal junction or the lead implant site, such as a Nissen fundoplication
3. Previous endoscopic intervention for the treatment of GERD and/or Barrett's esophagus
4. Hiatal hernia larger than 3 cm as determined by endoscopy
5. History of gastroparesis
6. Any non-GERD esophageal motility disorders that in the opinion of investigator precludes an anti-reflux procedure
7. History of or known esophageal stricture or significant esophageal anatomic abnormalities (obstructive lesions, etc.)
8. Barrett's esophagus or any grade of dysplasia
9. Documented history of esophagitis Grade C or D (LA Classification)
10. History of suspected or confirmed esophageal or gastric cancer
11. Esophageal or gastric varices
12. Symptoms of dysphagia more than once per week every week within the last 3 months
13. Unable to tolerate withdrawal from H2 Blockers or PPI medications
14. Suspected or known allergies to titanium, platinum, iridium, stainless steel, silicone, epoxy, or nylon
15. Body mass index (BMI) > 35 kg/m2
16. Any significant multisystem diseases
17. 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
18. 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
19. Significant cardiac arrhythmia or ectopy or significant cardiovascular disease (i.e. unstable angina pectoris, hemodynamically significant valvular disease, severe congestive heart failure), or any cardiac therapeutic intervention within the last 6 months.
20. Significant cerebrovascular event within the last 6 months
21. Existing implanted electrical stimulator (pacemaker, implantable cardioverter defibrillator, deep brain stimulator (DBS), bone growth or pelvic floor stimulators, drug pumps, etc.)
22. 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
23. Currently enrolled in other potentially confounding research
24. Active infection as determined by the investigator
25. History of any malignancy, other than basal cell carcinoma, in the last 2 years
26. Life expectancy less than 3 years aa. Diagnosed major psychiatric disorder (bipolar, schizophrenia, etc.) bb. Any condition that, at the discretion of the investigator or sponsor, would interfere with accurate interpretation of the study endpoints or preclude participation in the trial

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Crossover Assignment
• Masking: Quadruple

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Sham Comparator: Control Group; This group will undergo laparoscopic implantation surgery. The device will not be activated: Sham EndoStim stimulation for first six months of study. It will be activated at the Month 6 visit and provide lower esophageal stimulation from Month 6 thru end of study.	Procedure: Laparoscopic implantation surgery; Laparoscopic surgery to implant the pulse generator and bipolar lead.; Device: EndoStim stimulation from Month 6 thru end of study; Lower esophageal stimulation; Other Names: EndoStim Implantable Pulse Generator (IPG); lower esophageal stimulation; Device: Sham EndoStim stimulation for first six months of study; EndoStim device remains "off" (no stimulation delivered)
Experimental: Treatment Group; The group will undergo laparoscopic implantation surgery. The device will be activated two weeks post-implantation and the subject will receive EndoStim stimulation for first six months of study and continue with EndoStim stimulation from Month 6 thru end of study.	Procedure: Laparoscopic implantation surgery; Laparoscopic surgery to implant the pulse generator and bipolar lead.; Device: EndoStim stimulation from Month 6 thru end of study; Lower esophageal stimulation; Other Names: EndoStim Implantable Pulse Generator (IPG); lower esophageal stimulation; Device: EndoStim stimulation for first six months of study; Lower esophageal stimulation; Other Names: EndoStim Implantable Pulse Generator (IPG); lower esophageal stimulation

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Rate of device and/or procedure-related serious adverse events	Rate of occurrence of device and/or procedure-related serious adverse events after 12 months	12 months
Percentage of subjects achieving pH success (pH<4 for mo more than 5.3% of time or at least 50% improvement in pH compared to baseline)	Comparison between treatment and control group: percentage of subjects achieving pH success ((pH<4 for mo more than 5.3% of time or at least 50% improvement in pH compared to baseline)	Comparison of 6 months to baseline data

Collaborators and Investigators

• Sponsor: EndoStim Inc.
• Investigators: Principal Investigator: Nicholas J Shaheen, MD, MPH, University of North Carolina

Publications and helpful links

Helpful Links

• Study website

Study record dates

Study Major Dates

• Study Start: May 1, 2016
• Primary Completion (Actual): October 1, 2019
• Study Completion (Actual): October 1, 2019

Study Registration Dates

• First Submitted: April 15, 2016
• First Submitted That Met QC Criteria: April 20, 2016
• First Posted (Estimate): April 22, 2016

Study Record Updates

• Last Update Posted (Actual): October 18, 2019
• Last Update Submitted That Met QC Criteria: October 16, 2019
• Last Verified: October 1, 2019

More Information

Terms related to this study

• 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: CS-100

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