Effect of Long-Term Electrical Stimulation on LES Pressure and Esophageal Acid Exposure in Patients With GERD

Study Overview
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Brief Summary
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The EndoStim LES Stimulation System is an investigational device intended to improve the LES pressure and restore Lower Esophageal Sphincter (LES) function in individuals suffering from Gastroesophageal Reflux Disease (GERD).

Detailed Description
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EndoStim has developed an investigational medical device specifically designed to deliver electrical stimulation to the LES and has completed two clinical feasibility studies using an external version of the EndoStim stimulation system in fifteen subjects. In these two short-term studies, electrical stimulation resulted in significant increases in LES pressure. This study will further evaluate the safety of the procedure and its feasibility for use in this group of patients.

Official Title
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An Investigation of the Effect of Long-Term Electrical Stimulation on Lower Esophageal Sphincter (LES) Pressure and Esophageal Acid Exposure in Patients With Gastroesophageal Reflux Disease (GERD)

Conditions
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Gastroesophageal Reflux Disease

Intervention / Treatment
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* Device: EndoStim LES Stimulation System


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Subject is between 21 - 70 years of age. Subject has a history of heartburn, regurgitation or both for > 12 month prompting physician recommendation of continual daily use of PPI before study entry. Baseline GERD HRQL heartburn score following 10-14 days off PPI which is ≥ 20 and at least 10 points higher than the on PPI score Subject who are on standard medical therapy for 12 months or longer and experience discomfort or who are otherwise dissatisfied with GERD symptoms Subjects with a GERD condition that in the opinion of the PI justifies a minimally invasive reversible procedure prior to attempting anatomical change such as Nissen fundoplication Subject has an American Society of Anesthesiologists (ASA) Physical Status Classification I or II (or comparable local classification if any). Subject has exhibited excessive lower esophageal acid exposure during 24-hour pHmetry of antisecretory therapy performed within 6 months of screening visit; pH < 4 for > 5% of total time. Subject has a resting LES end expiratory pressure > 5mm Hg and < 15 mm Hg on a high resolution manometry within 6 months of enrollment. Subject has esophagitis ≤ Grade C (LA classification) on upper endoscopy within 6 months of enrollment. Subject has esophageal body contraction amplitude > 30 mmHg for > 50% of swallows and > 50% peristaltic contractions on high resolution manometry. Subject has signed the informed consent form and is able to adhere to study visit schedule. Exclusion Criteria: Subject has any non-GERD esophageal motility disorders. Subject has gastroparesis. Subject has any significant multisystem diseases. Subject has an autoimmune or a connective tissue disorder (e.g. scleroderma, dermatomyositis, Calcinosis-Raynaud's-Esophagus, Sclerodactyly Syndrome (CREST), Sjogren's Syndrome, Sharp's Syndrome), requiring therapy in the preceding 2 years. Subject has Barrett's epithelium (> M2; > C1) or any grade of dysplasia. Subject has a hiatal hernia larger than 3 cm. Subject has a body mass index (BMI) greater than 35 kg/m2. Subject has Type 1 diabetes mellitus Subject has uncontrolled Type 2 diabetes mellitus (T2DM) defined as HbA1c > 9.5 in the previous 6 months, or has T2DM for > 10 years. Subject has a history of suspected or confirmed esophageal or gastric cancer. Subject has esophageal or gastric varices. Subject has significant cardiac arrhythmia or ectopy or significant cardiovascular disease. Subject has an existing implanted electrical stimulator (e.g., pacemaker, AICD). Subject requires chronic anticoagulant therapy. Subject has dysphagia or esophageal peptic stricture, excluding Schatzki's ring. Subject of child-bearing potential who is pregnant or intends to become pregnant during the trial period. Subject is currently enrolled in other potentially confounding research. History of any malignancy in the last 2 years. History of previous esophageal or gastric surgery, including nissen fundoplication. Subject has any condition that, at the discretion of the investigator or sponsor, would preclude participation in the trial.

Ages Eligible for Study
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Minimum Age: 21 Years
Maximum Age: 70 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Intervention Model: Single Group Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Treatment Arm<br> | Device: EndoStim LES Stimulation System<br>* The EndoStim LES Stimulation System comprises three components: an electrical stimulation lead, an implantable pulse generator (IPG) and an external programmer. The IPG and stimulation lead are to be implanted within the subject's body using conventional laparoscopy. The device programmer is to be used by the study investigator and/or a company technical representative.<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Primary Safety Endpoint | Safety will be assessed by incidence and severity of adverse events through 6 months follow-up. Included in this assessment will be the proportion of subjects with any of the following outcomes between device implant and completion of the month 6 evaluation: (1) death, or (2) medical morbidity associated with the device and/or implantation procedure. | 6 months follow-up | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Secondary Efficacy Endpoints | Change in patient's GERD-HRQL from baseline to 6 months. | 6 months follow-up | 
| Secondary Efficacy Endpoints | Baseline pH values of % 24-hour esophageal pH< 4.0, and number of reflux events >1minute and >5 minute duration with the same on-stimulation pH parameters at 6 months. | 6 months follow-up | 
| Secondary Efficacy Endpoints | Change in symptoms frequency and severity at 6 months Vs. baseline as measured by patient symptom diary and patients quality of life measured by SF- 12. | 6 months follow-up | 
| Secondary Efficacy Endpoints | Change in antisecretory medication use as evaluated during the two weeks prior to the month 6 follow up compared to baseline. | 6 months follow-up | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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GERD, LES Pressure, Electrical Stimulation