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

• Sponsor: EndoStim Inc. (Industry)
• Overall Status: Terminated
• CT.gov ID: NCT02749071
• Collaborator: (none)
• Enrollment: 161
• Locations: 21
• Arms: 2
• Duration (Months): 41
• Patients Per Site: 7.7
• Patients Per Site Per Month: 0.2

Study Details

Study Description

Brief 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.

Condition or Disease	Intervention/Treatment	Phase
Gastroesophageal Reflux Disease (GERD); Reflux, Gastroesophageal; Gastroesophageal Reflux; Acid Reflux	Procedure: Laparoscopic implantation surgery; Device: EndoStim stimulation for first six months of study; Device: EndoStim stimulation from Month 6 thru end of study; Device: Sham EndoStim stimulation for first six months of study	N/A

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 Design

• Study Type: Interventional
• Actual Enrollment: 161 participants
• Allocation: Randomized
• Intervention Model: Crossover Assignment
• Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
• Primary Purpose: Treatment
• 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)
• Study Start Date: May 1, 2016
• Actual Primary Completion Date: Oct 1, 2019
• Actual Study Completion Date: Oct 1, 2019

Arms and Interventions

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 for first six months of study; Lower esophageal stimulation; Other Names: EndoStim Implantable Pulse Generator (IPG) lower esophageal stimulation ; Device: EndoStim stimulation from Month 6 thru end of study; Lower esophageal stimulation; Other Names: EndoStim Implantable Pulse Generator (IPG) lower esophageal stimulation

Outcome Measures

Primary Outcome Measures

1. Rate of device and/or procedure-related serious adverse events [12 months]

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

2. 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]

   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)

Eligibility Criteria

Criteria

• Ages Eligible for Study: 22 Years to 75 Years
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: No

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

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	St. Joseph's Hospital and Medical Center	Phoenix	Arizona	United States	85013
2	HonorHealth Research Institute	Scottsdale	Arizona	United States	85258
3	University of Southern California (USC)	Los Angeles	California	United States	90033
4	Stanford Center for Clinical Research	Stanford	California	United States	94305
5	Institute of Esophageal and Reflux Surgery	Englewood	Colorado	United States	80113
6	University of South Florida	Tampa	Florida	United States	33606
7	Cornell University Weill Medical College	New York	New York	United States	10021
8	Columbia University Medical Center	New York	New York	United States	10032
9	University of North Carolina	Chapel Hill	North Carolina	United States	27599
10	Carolinas HealthCare System	Charlotte	North Carolina	United States	28260
11	The MetroHealth System	Cleveland	Ohio	United States	44109
12	The Ohio State University Medical Center	Columbus	Ohio	United States	43210
13	Oregon Clinic	Portland	Oregon	United States	97213
14	Oregon Health Science University	Portland	Oregon	United States	97239
15	Allegheny Health Network Research Institute	Pittsburgh	Pennsylvania	United States	15224
16	Vanderbilt University Medical Center	Nashville	Tennessee	United States	37212
17	Baylor Scott & White Research Institute	Round Rock	Texas	United States	78665
18	Virginia Commonwealth University	Richmond	Virginia	United States	23298
19	Universitaire Ziekenhuizen Leuven	Leuven		Belgium
20	Clinical Trial Center Maastricht	Maastricht		Netherlands
21	University College London	London		United Kingdom

Sponsors and Collaborators

• EndoStim Inc.

Investigators

• Principal Investigator: Nicholas J Shaheen, MD, MPH, University of North Carolina

Study Documents (Full-Text)

None provided.

More Information

Additional Information:

• Study website

Publications

None provided.

• Responsible Party: EndoStim Inc.
• ClinicalTrials.gov Identifier: NCT02749071
• Other Study ID Numbers: CS-100
• First Posted: Apr 22, 2016
• Last Update Posted: Oct 18, 2019
• Last Verified: Oct 1, 2019

• Individual Participant Data (IPD) Sharing Statement: No
• Plan to Share IPD: No
• Additional relevant MeSH terms: Gastroesophageal Reflux; Esophagitis, Peptic

Study Results

No Results Posted as of Oct 18, 2019