Clinical trial NCT02514616: Electrical Stimulation Therapy (EST) of the Lower Esophageal Sphincter (GERD)
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
Overall status: TERMINATED
Phase: NA
Conditions: GERD
Keywords: Reflux
Reflux disease
Gastroesophageal reflux disease
Lower esophageal sphincter stimulation
Lead sponsor: Erasme University Hospital
Sponsor class: OTHER
Collaborators: name: EndoStim Inc.
First posted: 2015-08-04
Enrollment: 1
Sex: ALL
Minimum age (years): 18
Maximum age (years): 70
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

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.

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.)

Primary outcomes:
measure: 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)
timeFrame: 14 weeks
Secondary outcomes:
measure: Safety (Rate of occurrence of device- and procedure-related adverse events)
timeFrame: 12 months
measure: Number of subjects achieving GERD symptom success
timeFrame: 12 months
measure: Reflux symptoms measured by GERD-HRQL score
timeFrame: 6 months
measure: Reflux symptoms measured by GERD-HRQL score
timeFrame: 12 months
measure: Number of subjects able to stop regular use of acid-suppression
timeFrame: 12 months
measure: Number of subjects able to stop all use of acid-suppression medication
timeFrame: 12 months
measure: Percentage of asymptomatic patients
timeFrame: 14 weeks
measure: Incidence of reflux esophagitis
timeFrame: 12 months
measure: Quality of life measured by EQ-5D EuroQol score
timeFrame: 14 weeks
measure: Quality of life measured by EQ-5D score
timeFrame: 6 months
measure: Quality of life measured by EQ-5D score
timeFrame: 12 months
measure: Efficacy of EST on acid reflux measured by esophageal pH
timeFrame: 14 weeks
measure: Efficacy of EST on acid reflux measured by DeMeester score
timeFrame: 14 weeks
measure: Percentage of subjects achieving pH success
timeFrame: 14 weeks
measure: Efficacy of EST on reflux episodes measured by esophageal impedance
timeFrame: 14 weeks
measure: Difference in lower esophageal sphincter (LOS) pressure and integrated relaxation pressure at 4 seconds (IRP4s) in Treatment and Control groups
timeFrame: 14 weeks
measure: Comparison of GERD-HRQL scores in Treatment and Control groups
timeFrame: 14 weeks
measure: Comparison of quality of life measured by EQ-5D in Treatment and Control groups
timeFrame: 14 weeks
Other outcomes:
Locations:
city: Brussels
country: Belgium
facility: Gastroenterology Department, Erasme University Hospital
city: Lyon
country: France
facility: Hôpital Edouard Herriot, Service d'Explorations Fonctionnelles Digestives, Pavillons H et L, 5 Place d'Arsonval
state: Lyon Cedex 3
Study officials:
References: