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

Primary Purpose

GERD

Status
Terminated
Phase
Not Applicable
Locations
International
Study Type
Interventional
Intervention
Laparoscopic IPG and lead implant procedure
Active Electric Stimulation Therapy
Delayed Electric Stimulation Therapy
Sponsored by
Erasme University Hospital
About
Eligibility
Locations
Arms
Outcomes
Full info

About this trial

This is an interventional treatment trial for GERD focused on measuring Reflux, Reflux disease, Gastroesophageal reflux disease, Lower esophageal sphincter stimulation

Eligibility Criteria

18 Years - 70 Years (Adult, Older Adult)All SexesDoes not accept healthy volunteers

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.)

Sites / Locations

  • Gastroenterology Department, Erasme University Hospital
  • Hôpital Edouard Herriot, Service d'Explorations Fonctionnelles Digestives, Pavillons H et L, 5 Place d'Arsonval

Arms of the Study

Arm 1

Arm 2

Arm Type

Active Comparator

Sham Comparator

Arm Label

Active Electric Stimulation Therapy

Delayed Electric Stimulation Therapy

Arm Description

The subject receives Active Electric Stimulation Therapy for 12 weeks, 2 weeks after laparoscopic IPG and lead implant procedure. The subject and physician will be blinded to the randomization group assignment. The subject continues on stimulation treatment after 14 weeks and an extended open-label follow-up phase includes annual visits through 5 years.

The subject receives no active Electric Stimulation Therapy for 12 weeks, 2 weeks after laparoscopic IPG and lead implant procedure. The subject and physician will be blinded to the randomization group assignment. The subject will receive Active Electric Stimulation Therapy at week 14 visit, and an extended open-label follow-up phase includes annual visits through 5 years.

Outcomes

Primary Outcome Measures

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)

Secondary Outcome Measures

Safety (Rate of occurrence of device- and procedure-related adverse events)
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
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)
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)
Number of subjects able to stop regular use of acid-suppression
Defined as 50% or more days without PPI use
Number of subjects able to stop all use of acid-suppression medication
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.
Incidence of reflux esophagitis
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.
Quality of life measured by EQ-5D score
Difference in patient's EQ-5D score, compared to pre-implantation score on and off PPI.
Quality of life measured by EQ-5D score
Difference in patient's EQ-5D score, compared to pre-implantation score on and off PPI.
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)).
Efficacy of EST on acid reflux measured by DeMeester score
Difference in DeMeester score in Treatment and Control groups.
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.
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.
Difference in lower esophageal sphincter (LOS) pressure and integrated relaxation pressure at 4 seconds (IRP4s) in Treatment and Control groups
Comparison of GERD-HRQL scores in Treatment and Control groups
Comparison of quality of life measured by EQ-5D in Treatment and Control groups

Full Information

First Posted
July 24, 2015
Last Updated
November 19, 2015
Sponsor
Erasme University Hospital
Collaborators
EndoStim Inc.
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1. Study Identification

Unique Protocol Identification Number
NCT02514616
Brief Title
Electrical Stimulation Therapy (EST) of the Lower Esophageal Sphincter (GERD)
Acronym
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
Study Type
Interventional

2. Study Status

Record Verification Date
November 2015
Overall Recruitment Status
Terminated
Why Stopped
Early termination due to a suspension of financial support
Study Start Date
January 2015 (undefined)
Primary Completion Date
November 2015 (Actual)
Study Completion Date
November 2015 (Actual)

3. Sponsor/Collaborators

Responsible Party, by Official Title
Principal Investigator
Name of the Sponsor
Erasme University Hospital
Collaborators
EndoStim Inc.

4. Oversight

Data Monitoring Committee
No

5. Study Description

Brief 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.
Detailed 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.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
GERD
Keywords
Reflux, Reflux disease, Gastroesophageal reflux disease, Lower esophageal sphincter stimulation

7. Study Design

Primary Purpose
Treatment
Study Phase
Not Applicable
Interventional Study Model
Parallel Assignment
Masking
ParticipantCare ProviderInvestigator
Allocation
Randomized
Enrollment
1 (Actual)

8. Arms, Groups, and Interventions

Arm Title
Active Electric Stimulation Therapy
Arm Type
Active Comparator
Arm Description
The subject receives Active Electric Stimulation Therapy for 12 weeks, 2 weeks after laparoscopic IPG and lead implant procedure. The subject and physician will be blinded to the randomization group assignment. The subject continues on stimulation treatment after 14 weeks and an extended open-label follow-up phase includes annual visits through 5 years.
Arm Title
Delayed Electric Stimulation Therapy
Arm Type
Sham Comparator
Arm Description
The subject receives no active Electric Stimulation Therapy for 12 weeks, 2 weeks after laparoscopic IPG and lead implant procedure. The subject and physician will be blinded to the randomization group assignment. The subject will receive Active Electric Stimulation Therapy at week 14 visit, and an extended open-label follow-up phase includes annual visits through 5 years.
Intervention Type
Procedure
Intervention Name(s)
Laparoscopic IPG and lead implant procedure
Other Intervention Name(s)
EndoStim
Intervention Description
EST placement
Intervention Type
Device
Intervention Name(s)
Active Electric Stimulation Therapy
Other Intervention Name(s)
EndoStim
Intervention Description
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.
Intervention Type
Device
Intervention Name(s)
Delayed Electric Stimulation Therapy
Other Intervention Name(s)
EndoStim
Intervention Description
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.
Primary Outcome Measure Information:
Title
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)
Description
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)
Time Frame
14 weeks
Secondary Outcome Measure Information:
Title
Safety (Rate of occurrence of device- and procedure-related adverse events)
Time Frame
12 months
Title
Number of subjects achieving GERD symptom success
Description
Improvement in the total GERD-HRQL score of 50% or more compared to pre-implantation score off PPI
Time Frame
12 months
Title
Reflux symptoms measured by GERD-HRQL score
Description
Mean improvement in the composite GERD-HRQL scores from baseline measured after at least 14 days off proton pump inhibitors (PPIs)
Time Frame
6 months
Title
Reflux symptoms measured by GERD-HRQL score
Description
Mean improvement in the composite GERD-HRQL scores from baseline measured after at least 14 days off proton pump inhibitors (PPIs)
Time Frame
12 months
Title
Number of subjects able to stop regular use of acid-suppression
Description
Defined as 50% or more days without PPI use
Time Frame
12 months
Title
Number of subjects able to stop all use of acid-suppression medication
Time Frame
12 months
Title
Percentage of asymptomatic patients
Description
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.
Time Frame
14 weeks
Title
Incidence of reflux esophagitis
Time Frame
12 months
Title
Quality of life measured by EQ-5D EuroQol score
Description
Difference in patient's EQ-5D score, compared to pre-implantation score on and off PPI.
Time Frame
14 weeks
Title
Quality of life measured by EQ-5D score
Description
Difference in patient's EQ-5D score, compared to pre-implantation score on and off PPI.
Time Frame
6 months
Title
Quality of life measured by EQ-5D score
Description
Difference in patient's EQ-5D score, compared to pre-implantation score on and off PPI.
Time Frame
12 months
Title
Efficacy of EST on acid reflux measured by esophageal pH
Description
Difference in % 24 hour esophageal pH<4 in Treatment and Control groups (total, upright, supine, postprandial (2h)).
Time Frame
14 weeks
Title
Efficacy of EST on acid reflux measured by DeMeester score
Description
Difference in DeMeester score in Treatment and Control groups.
Time Frame
14 weeks
Title
Percentage of subjects achieving pH success
Description
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.
Time Frame
14 weeks
Title
Efficacy of EST on reflux episodes measured by esophageal impedance
Description
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.
Time Frame
14 weeks
Title
Difference in lower esophageal sphincter (LOS) pressure and integrated relaxation pressure at 4 seconds (IRP4s) in Treatment and Control groups
Time Frame
14 weeks
Title
Comparison of GERD-HRQL scores in Treatment and Control groups
Time Frame
14 weeks
Title
Comparison of quality of life measured by EQ-5D in Treatment and Control groups
Time Frame
14 weeks

10. Eligibility

Sex
All
Minimum Age & Unit of Time
18 Years
Maximum Age & Unit of Time
70 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
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.)
Facility Information:
Facility Name
Gastroenterology Department, Erasme University Hospital
City
Brussels
ZIP/Postal Code
1070
Country
Belgium
Facility Name
Hôpital Edouard Herriot, Service d'Explorations Fonctionnelles Digestives, Pavillons H et L, 5 Place d'Arsonval
City
Lyon
State/Province
Lyon Cedex 3
ZIP/Postal Code
69437
Country
France

12. IPD Sharing Statement

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

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