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

Gastroesophageal Reflux Clinical Trial

Official title:

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)

Clinical Trial Details — Status: Terminated

Administrative data

• NCT number: NCT02749071
• Other study ID #: CS-100
• Status: Terminated
• Phase: N/A
• Start date: May 2016
• Est. completion date: October 2019

Study information

• Verified date: October 2019
• Source: EndoStim Inc.
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

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.

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.

Recruitment information / eligibility

• Status: Terminated
• Enrollment: 161
• Est. completion date: October 2019
• Est. primary completion date: October 2019
• Accepts healthy volunteers: No
• Gender: All
• Age group: 22 Years to 75 Years

Eligibility

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

Related Conditions & MeSH terms

• Acid Reflux
• Esophagitis, Peptic
• Gastroesophageal Reflux
• Gastroesophageal Reflux Disease (GERD)
• Reflux, Gastroesophageal

Intervention

Procedure:
• Laparoscopic implantation surgery
Laparoscopic surgery to implant the pulse generator and bipolar lead.

Device:
• EndoStim stimulation for first six months of study
Lower esophageal stimulation
• EndoStim stimulation from Month 6 thru end of study
Lower esophageal stimulation
• Sham EndoStim stimulation for first six months of study
EndoStim device remains "off" (no stimulation delivered)

Locations

Country	Name	City	State
Belgium	Universitaire Ziekenhuizen Leuven	Leuven
Netherlands	Clinical Trial Center Maastricht	Maastricht
United Kingdom	University College London	London
United States	University of North Carolina	Chapel Hill	North Carolina
United States	Carolinas HealthCare System	Charlotte	North Carolina
United States	The MetroHealth System	Cleveland	Ohio
United States	The Ohio State University Medical Center	Columbus	Ohio
United States	Institute of Esophageal and Reflux Surgery	Englewood	Colorado
United States	University of Southern California (USC)	Los Angeles	California
United States	Vanderbilt University Medical Center	Nashville	Tennessee
United States	Columbia University Medical Center	New York	New York
United States	Cornell University Weill Medical College	New York	New York
United States	St. Joseph's Hospital and Medical Center	Phoenix	Arizona
United States	Allegheny Health Network Research Institute	Pittsburgh	Pennsylvania
United States	Oregon Clinic	Portland	Oregon
United States	Oregon Health Science University	Portland	Oregon
United States	Virginia Commonwealth University	Richmond	Virginia
United States	Baylor Scott & White Research Institute	Round Rock	Texas
United States	HonorHealth Research Institute	Scottsdale	Arizona
United States	Stanford Center for Clinical Research	Stanford	California
United States	University of South Florida	Tampa	Florida

Sponsors (1)

Lead Sponsor	Collaborator
EndoStim Inc.

Countries where clinical trial is conducted

United States,  Belgium,  Netherlands,  United Kingdom, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	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
Primary	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