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
Overview
- Phase
- Not Applicable
- Status
- Terminated
- Sponsor
- Erasme University Hospital
- Enrollment
- 1
- Locations
- 2
- Primary Endpoint
- 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)
Overview
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.
Study Design
- Study Type
- Interventional
- Allocation
- Randomized
- Intervention Model
- Parallel
- Primary Purpose
- Treatment
- Masking
- Triple (Participant, Care Provider, Investigator)
Eligibility Criteria
- Ages
- 18 Years to 70 Years (Adult, Older Adult)
- Sex
- All
- Accepts Healthy Volunteers
- No
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
Outcomes
Primary Outcomes
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)
Time Frame: 14 weeks
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 Outcomes
- Number of subjects able to stop regular use of acid-suppression(12 months)
- Number of subjects achieving GERD symptom success(12 months)
- Reflux symptoms measured by GERD-HRQL score(12 months)
- Efficacy of EST on acid reflux measured by esophageal pH(14 weeks)
- Safety (Rate of occurrence of device- and procedure-related adverse events)(12 months)
- Quality of life measured by EQ-5D EuroQol score(14 weeks)
- Efficacy of EST on acid reflux measured by DeMeester score(14 weeks)
- Percentage of subjects achieving pH success(14 weeks)
- Efficacy of EST on reflux episodes measured by esophageal impedance(14 weeks)
- Comparison of quality of life measured by EQ-5D in Treatment and Control groups(14 weeks)
- Incidence of reflux esophagitis(12 months)
- Quality of life measured by EQ-5D score(12 months)
- Difference in lower esophageal sphincter (LOS) pressure and integrated relaxation pressure at 4 seconds (IRP4s) in Treatment and Control groups(14 weeks)
- Number of subjects able to stop all use of acid-suppression medication(12 months)
- Comparison of GERD-HRQL scores in Treatment and Control groups(14 weeks)
- Percentage of asymptomatic patients(14 weeks)
Investigators
Hubert Louis
Hubert LOUIS, pHD
Erasme University Hospital