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

EndoStim Inc.161 enrolled

Overview

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.

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

Allocation

RANDOMIZED

Purpose

TREATMENT

Masking

QUADRUPLE

Enrollment

161

Conditions

Interventions

Laparoscopic implantation surgery with or without crural repairPROCEDURE

Laparoscopic surgery with or without crural repair to implant the pulse generator and bipolar lead.

EndoStim stimulation for first six months of studyDEVICE

Lower esophageal stimulation

EndoStim stimulation from Month 6 thru end of studyDEVICE

Lower esophageal stimulation

Sham EndoStim stimulation for first six months of studyDEVICE

EndoStim device remains "off" (no stimulation delivered)

Eligibility

Sex: ALLMin age: 22 YearsMax age: 75 Years

Medical Language ↔ Plain English

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

Locations (21)

St. Joseph's Hospital and Medical Center

Phoenix, Arizona, United States

HonorHealth Research Institute

Scottsdale, Arizona, United States

University of Southern California (USC)

Los Angeles, California, United States

Stanford Center for Clinical Research

Stanford, California, United States

Institute of Esophageal and Reflux Surgery

Englewood, Colorado, United States

University of South Florida

Tampa, Florida, United States

Cornell University Weill Medical College

New York, New York, United States

Columbia University Medical Center

New York, New York, United States

University of North Carolina

Chapel Hill, North Carolina, United States

Carolinas HealthCare System

Charlotte, North Carolina, United States

...and 11 more locations

Outcomes

Primary Outcomes

Primary Safety Endpoint: Rate of Device and/or Procedure-related Serious Adverse Events After 12 Months Post-implant

Rate of occurrence of device and/or procedure-related serious adverse events after 12 months of implant

Time frame: 12 months after implant

Primary Efficacy Endpoint: Percentage of Subjects Achieving pH Success (pH<4 for 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 more than 5.3% of time or at least 50% improvement in pH compared to baseline)

Time frame: Comparison of 6 months to baseline data

Secondary Outcomes

Secondary Endpoint (Open-label, 12 Months on Stimulation): GERD-HRQL Score (Off-PPI/H2 Blocker)

The secondary efficacy endpoint was the number of subjects achieving GERD symptom success defined as an improvement in the composite GERD Health-related Quality of Life (GERD-HRQL) patient reported outcome questionnaire score of 50% or more after 12 months on stimulation compared to the baseline off-PPI or H2 blocker composite GERD-HRQL score. Questions regarding heartburn severity and difficulty swallowing are asked on scale of 0 to 5: 0 = No symptoms; 1 = Symptoms noticeable but not bothersome; 2 = Symptoms noticeable and bothersome but not every day; 3 = Symptoms bothersome every day; 4 = Symptoms affect daily activities; and 5 = Symptoms are incapacitating - unable to do activities. The composite score is calculated by adding the responses to the individual questions. The minimum score possible is 0 and the maximum score is 45.