Electrical Stimulation Therapy (EST) of the Lower Esophageal Sphincter (GERD)

GERD Clinical Trial

— EST-SHAM-EUR  

Official title:

Electrical Stimulation Therapy (EST) of the Lower Esophageal Sphincter: a Multicenter, Randomized, Double-blind, Sham-controlled Parallel-group Trial Evaluating Short Term Efficacy of EndoStim Device on GERD

Clinical Trial Details — Status: Terminated

Administrative data

• NCT number: NCT02514616
• Other study ID #: ESE-001
• Status: Terminated
• Phase: N/A
• First received: July 24, 2015
• Last updated: November 19, 2015
• Start date: January 2015
• Est. completion date: November 2015

Study information

• Verified date: November 2015
• Source: Erasme University Hospital
• Contact: n/a
• Is FDA regulated: No
• Health authority: Belgium: Federal Agency for Medicines and Health Products, FAMHP
• Study type: Interventional

Clinical Trial Summary

The investigational device that will be used in this trial is the EndoStim® Lower Esophageal Sphincter (LES) Stimulation System.

The purpose of this trial is to evaluate the safety and the effectiveness of electrical stimulation therapy (EST) on the lower esophageal sphincter (LES) in the treatment of subjects with gastroesophageal reflux disease (GERD).

The study population will consist of subjects diagnosed with pathological GERD as defined by abnormal pH and who complain of heartburn, regurgitation or both for > 6 months, on a daily PPI use.

Description:

Study Design:

Multicenter, randomized, double-blind, sham-controlled study. All subjects undergo screening and baseline visits, followed by system implantation, and randomization after 2 weeks to either a treatment Group (stimulation) or Control Group (delayed stimulation).

Randomized subjects complete a 10-week, double-blind phase. At the 14-week visit, subjects are unblinded, control group subjects begin receiving stimulation, and all subjects are followed for an additional 9-month open-label treatment phase.

Subjects continue receiving stimulation for an extended follow-up phase involving annual visits through 5 years.

Study Visits:

Screening and baseline visits. Laparoscopic implantable pulse generator (IPG) and lead implant procedure. Post-implant follow-up office visits at 2 weeks/randomization, 6, 10, 14, 24 and 48 weeks, followed by annual visits through 5 years.

Sample Size and Scope:

Forty-six subjects will be implanted and followed to 12 months after stimulation treatment at 3 investigational sites.

Recruitment information / eligibility

• Status: Terminated
• Enrollment: 1
• Est. completion date: November 2015
• Est. primary completion date: November 2015
• Accepts healthy volunteers: No
• Gender: Both
• Age group: 18 Years to 70 Years

Eligibility

Inclusion Criteria:

• Subject able and willing to provide written informed consent

• Subject able and willing to comply with required study procedures and follow-up schedule

• Typical symptoms of GERD (regurgitation and/or heartburn) for longer than 6 months, heartburn responding to PPI therapy. Subject may also complain of atypical symptoms of GERD that may persist on PPI

• Daily dose of PPI or other acid neutralization drugs because of PPI intolerance

• Baseline visit GERD-HRQL score = 20 following 14 days off-PPI and at least 10 points higher than their on-PPI (or other acid-neutralization drugs) GERD-HRQL score recorded during the Screening Visit

• Excessive lower esophageal acid exposure during pH monitoring (defined as distal esophageal pH < 4 for > 5.0% of the monitoring time) performed after 14 days off PPIs

• Subject is a suitable surgical candidate able to undergo general anesthesia and laparoscopic surgery.

Exclusion Criteria:

• Previous EndoStim LES System implant and/or implant attempt

• Previous esophageal surgery, including Nissen fundoplication

• Previous endoscopic intervention for the treatment of GERD and/or Barrett's esophagus

• Hiatal hernia larger than 2 cm as determined by any diagnostic investigation (i.e., endoscopy, manometry or laparoscopic visualization)

• Gastroparesis

• Any non-GERD esophageal motility disorders

• Esophageal stricture or significant esophageal anatomic abnormalities

• Barrett's epithelium or any grade of dysplasia

• Documented history of esophagitis Grade C or D (LA Classification)

• History of suspected or confirmed esophageal or gastric cancer

• Esophageal or gastric varices

• Symptoms of dysphagia more than once per week within the last 3 months

• Suspected or known allergies to titanium, platinum, iridium, stainless steel, silicone, epoxy, or nylon

• Body mass index (BMI) > 35 kg/m2

• Any significant multisystem diseases

• 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

• 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, or has T2DM for > 10 years

• Significant cardiac arrhythmia or ectopy or significant cardiovascular disease (i.e. unstable angina pectoris, hemodynamically significant valvular disease, severe congestive heart failure), or cardiac therapeutic intervention within the last 6 months.

• Significant cerebrovascular event within the last 6 months

• Existing implanted electrical stimulator (pacemaker, implantable cardioverter defibrillator, deep brain stimulator (DBS), bone growth or pelvic floor stimulators, drug pumps, etc.)

• Chronic anticoagulant therapy

• 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

• Subject is currently enrolled in other potentially confounding research

• Active infection as determined by the investigator

• History of any malignancy in the last 2 years

• Life expectancy less than 3 years

• Diagnosed major psychiatric disorder (bipolar, schizophrenia, etc.)

Study Design

Allocation: Randomized, Endpoint Classification: Safety/Efficacy Study, Intervention Model: Parallel Assignment, Masking: Double Blind (Subject, Caregiver, Investigator), Primary Purpose: Treatment

Related Conditions & MeSH terms

• GERD

Intervention

Procedure:
• Laparoscopic IPG and lead implant procedure
EST placement

Device:
• Active Electric Stimulation Therapy
Device programming by the technician to deliver the EST system active (Treatment group) or no stimulation (Control group) for the following 12 weeks, at the 2 weeks visit.
• Delayed Electric Stimulation Therapy
Device programming by the technician to deliver the EST system no stimulation for the following 12 weeks at the 2 weeks visit. Active Electric Stimulation Therapy will be programmed at the 14 weeks visit.

Locations

Country	Name	City	State
Belgium	Gastroenterology Department, Erasme University Hospital	Brussels
France	Hôpital Edouard Herriot, Service d'Explorations Fonctionnelles Digestives, Pavillons H et L, 5 Place d'Arsonval	Lyon	Lyon Cedex 3

Sponsors (2)

Lead Sponsor	Collaborator
Erasme University Hospital	EndoStim Inc.

Countries where clinical trial is conducted

Belgium,  France, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Efficacy of EST on GERD symptoms (mean improvement in the GERD- health-related quality of life (HRQL) scores from baseline in control and treatment groups)	Comparison between Treatment and Control Groups of the mean improvement in the composite GERD-HRQL scores from baseline measured after at least 14 days off proton pump inhibitors (PPIs)	14 weeks	No
Secondary	Safety (Rate of occurrence of device- and procedure-related adverse events)		12 months	Yes
Secondary	Number of subjects achieving GERD symptom success	Improvement in the total GERD-HRQL score of 50% or more compared to pre-implantation score off PPI	12 months	No
Secondary	Reflux symptoms measured by GERD-HRQL score	Mean improvement in the composite GERD-HRQL scores from baseline measured after at least 14 days off proton pump inhibitors (PPIs)	6 months	No
Secondary	Reflux symptoms measured by GERD-HRQL score	Mean improvement in the composite GERD-HRQL scores from baseline measured after at least 14 days off proton pump inhibitors (PPIs)	12 months	No
Secondary	Number of subjects able to stop regular use of acid-suppression	Defined as 50% or more days without PPI use	12 months	No
Secondary	Number of subjects able to stop all use of acid-suppression medication		12 months	No
Secondary	Percentage of asymptomatic patients	Defined as an improvement in their total GERD-HRQL score of 50% or more compared to pre-implantation score off PPI) in treatment and control groups, off-PPI for the last 2 weeks.	14 weeks	No
Secondary	Incidence of reflux esophagitis		12 months	No
Secondary	Quality of life measured by EQ-5D EuroQol score	Difference in patient's EQ-5D score, compared to pre-implantation score on and off PPI.	14 weeks	No
Secondary	Quality of life measured by EQ-5D score	Difference in patient's EQ-5D score, compared to pre-implantation score on and off PPI.	6 months	No
Secondary	Quality of life measured by EQ-5D score	Difference in patient's EQ-5D score, compared to pre-implantation score on and off PPI.	12 months	No
Secondary	Efficacy of EST on acid reflux measured by esophageal pH	Difference in % 24 hour esophageal pH<4 in Treatment and Control groups (total, upright, supine, postprandial (2h)).	14 weeks	No
Secondary	Efficacy of EST on acid reflux measured by DeMeester score	Difference in DeMeester score in Treatment and Control groups.	14 weeks	No
Secondary	Percentage of subjects achieving pH success	Defined as normalization (pH < 4 for no more than 4.1% of monitoring time) or > 50% improvement in their distal esophageal acid exposure compared to their baseline off-PPI distal esophageal pH.	14 weeks	No
Secondary	Efficacy of EST on reflux episodes measured by esophageal impedance	Difference in the number of reflux episodes (total, upright, supine, postprandial (2h), acidic, weakly acidic, weakly alkaline, and proximal extent (15 cm) in Treatment and Control groups.	14 weeks	No
Secondary	Difference in lower esophageal sphincter (LOS) pressure and integrated relaxation pressure at 4 seconds (IRP4s) in Treatment and Control groups		14 weeks	No
Secondary	Comparison of GERD-HRQL scores in Treatment and Control groups		14 weeks	No
Secondary	Comparison of quality of life measured by EQ-5D in Treatment and Control groups		14 weeks	No