An Investigation of Electrical Stimulation on Gastroesophageal Reflux Disease (GERD) in Patients After Sleeve Gastrectomy

Study Overview
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Brief Summary
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Sleeve gastrectomy (SG) has gained popularity as both a staged and a definitive procedure for morbid obesity due to its technical simplicity, low-morbidity and excellent results both for weight loss and control of metabolic syndrome. There are however reports of SG worsening pre-existing GERD or causing new-onset GERD. Because of this, patients with pre-existing GERD have been denied the benefits of SG. In addition, patients that develop post-op GERD cannot undergo traditional anti-reflux surgery since the gastric fundus that is required for fundoplication is removed during the SG. Hence, patients with post-SG GERD not adequately controlled with medication can only opt for the more invasive gastric bypass procedure as their only surgical treatment option. In a recently reported case study, an obese patient with severe GERD successfully treated with EndoStim underwent SG and maintained adequate GERD control with continued use of LES stimulation therapy. However electrical stimulation was not yet tested systematically in patients with prior gastric operation such as sleeve gastrectomy. This study will test the hypothesis that electrical stimulation is effective in control of GERD associated with SG.

Official Title
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An Investigation of Electrical Stimulation on Gastroesophageal Reflux Disease (GERD) in Patients After Sleeve Gastrectomy

Conditions
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GERD, Sleeve Gastrectomy

Intervention / Treatment
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* Device: LES-Stimulation Device


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Subject is between 18 - 80 years of age. Subject underwent a sleeve gastrectomy minimum one year prior to enrollment (in order to have reached a stable weight loss plateau). Subject has a history of heartburn, regurgitation or both for >6 month prompting physician recommendation of continual daily use of PPI after sleeve gastrectomy. Baseline off-PPI GERD-HRQL score ≥ 20 following 10-14 days off PPI Baseline off-PPI GERD-HRQLscore is at least 5 points higher than the on-PPI score or a positive relationship between the occurrence of their primary symptom during the pH impedance monitoring (symptom association probability ≥ 95% or a SI score ≥ 50%) is present. Subject who are on standard medical therapy for 6 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 a more drastic procedure such as a gastric bypass. Subject has exhibited excessive lower esophageal acid exposure during 24-hour pH-metry of antisecretory therapy performed within 6 months of screening visit; pH < 4 for > 6% of total time. Subject has a resting LES end expiratory pressure ≥ 5mmHg on manometry performed within 6 months of enrollment. Subject has no esophagitis or esophagitis ≤ Grade C (LA classification) on upper endoscopy within 6 months of enrollment. Subject has esophageal body contraction amplitude > 30 mmHg for >30% of swallows and > 30% peristaltic contractions on 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 evidence of obstruction or stricture in the gastric sleeve by a barium swallow and endoscopy. Subject has any significant multisystem diseases. Subject has an autoimmune or a connective tissue disorder (e.g. scleroderma, dematomyositis, 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. Subject has any condition that, at the discretion of the investigator, would preclude participation in the trial. Weight change of +/- 10% of the EWL (Excess Weight Loss) in the 3 months prior to enrollment.

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 80 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
Allocation: Non-Randomized
Intervention Model: Single Group Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Electrical Stimulation Therapy<br> | Device: LES-Stimulation Device<br> <br> * Other names: EndoStim b.v.;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| The incidence and severity of any complications that are associated with the investigational stimulation device throughout the follow-up period. |  | up to 12 month follow-up | 
| Efficacy - Disease specific quality of life | The change in patient's GERD-HRQL, where applicable, from baseline (as measured while off PPI) . | Baseline, 6 and 12 month follow up | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| pH-monitoring | The change in 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 and at 12 months. | Baseline, 6 and 12 month FU | 
| Questionnairres, symptom diary | Change in symptoms frequency and severity at 6 months vs. baseline and at 12 months vs. baseline as measured by patient symptom diary, structured GI questionnaire, and patients quality of life measured by SF-12. | baseline, 6 and 12 month FU | 
| Anti-secretory medication use | Change in anti-secretory medication use as evaluated during the two weeks prior to the 6 mo and 12 mo follow up compared to baseline. | Baseline, 6 and 12 month FU | 
| HR-manometry | Change in LES end expiratory pressure (LESPpre) and the on-stimulation LES end expiratory pressure (LESPpost) at 6 months and 12 months in mmHg. | Baseline, 6 and 12 month FU | 

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