Endomina Suturing Device as a Treatment of GERD.

Study Overview
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Brief Summary
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Gastroesophageal Reflux Disease (GERD) is a common problem affecting 10-20% of the population in the Western World. Surgical therapy is able to restore the EGJ barrier function against reflux of the gastric content, decreases symptoms and improves the quality of life in GERD patients. However, there remain concerns regarding postoperative adverse events and the durability of the surgical procedure. The ability to perform endoscopic full-thickness plications with Endomina-v2 will be used to assess safety and feasibility of the procedure in reducing GERD in patients suffering with chronic GERD, unsatisfied with PPIs, and/or complaining of persistent GERD symptoms despite PPI use.

Detailed Description
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Gastroesophageal Reflux Disease (GERD) is a common problem affecting 10-20% of the population in the Western World. Approximately 250 million subjects worldwide and 30 million subjects in the US suffer from GERD. Among the 12 million Americans who suffer from daily heart-burn (the main symptom of GERD) almost 5 million do not respond completely to medications and many more do not want or cannot take medications due to side-effects (1). The goals of treatment in GERD are to relieve symptoms, heal esophagitis if present, prevent recurrence of symptoms and esophagitis, and prevent complications. Medical acid-suppressive therapy with proton pump inhibitors (PPIs) heals esophagitis, relieves symptoms and improves quality of life. However, acid suppressive therapy does not correct the underlying pathophysiology of dysfunction of the lower esophageal sphincter and hence symptoms of reflux due to weakly acidic or non-acid reflux persist in the majority of subjects who present with symptoms persisting on PPIs (regurgitations) (2). Abnormalities in the structure and function of the esophago-gastric junction (EGJ) such as a permanently open EGJ, a hiatal hernia, a hypotensive lower esophageal sphincter (LES), and transient LES relaxations (t-LESR) are the main pathophysiologic mechanisms leading to GERD (3). Surgical therapy is able to restore the EGJ barrier function against reflux of the gastric content, decreases symptoms and improves the quality of life in GERD patients (4,5). However, there remain concerns regarding postoperative adverse events and the durability of the surgical procedure (6,7). The results reported from operations performed in community hospital lower volume centers have been different than those achieved in centers of excellence. It has been reported that between 23% and 62% of patients who have undergone laparoscopic Nissen fundoplication use acid suppression medications at long-term follow-up. Due to these issues patient and physician acceptance of surgical procedures remains low and is mainly limited to patients with severe GERD or those non-responsive to medications. For these reasons, less invasive endoscopic techniques to treat GERD have been developed during the last 2 decades, which may be categorized into 3 groups: (1) sewing/plication at the cardia and EGJ, (2) radiofrequency (RF) thermal therapy to the LES, and (3) injection/implantation of biopolymers at the EGJ. Minimally invasive endoluminal procedures for GERD are designed to provide long-lasting symptom relief and abolish or lessen medication dependency. Most endoluminal modalities that were introduced into clinical practice have failed due to lack of long-term efficacy, complications, or interruption of commercialization due to financial difficulties of the companies that developed the techniques (8,9). Endoscopic sewing/plication techniques comprised mucosal plications (Endocinch) that were not clinically useful because the plications were not durable, and full-thickness (serosa-to-serosa) plications allowing prolonged durability (NDO Plicator device and Esophyx device). The data from the RCTs with Plicator device were encouraging and the finding of better results with multiple plications without an increase in adverse events supported that this device could have clinical utility. However, the company ceased operations in 2008 and the device is no longer clinically available (10). Transoral incisionless fundoplication (TIF) using Esophyx showed promising results in open studies (11). However, long-term follow-up revealed that a majority of patients required either ongoing PPI use or were referred for LNF owing to persistent symptoms (12). Endomina-v2 (Endo Tools Therapeutics SA, Rue Auguste Piccard 48, 6041 GOSSELIES, Belgium) is a CE marked device that can be attached to an endoscope inside the body and allows manipulation of angulated tools during a peroral intervention. It offers the possibility to perform transoral surgical full thickness sutures and transoral endoscopic gastroplasty has shown to be safe and effective at mid-term follow-up in obese patients (13). The ability to perform endoscopic full-thickness plications with Endomina-v2 will be used to assess safety and feasibility of the procedure in reducing GERD in patients suffering with chronic GERD, unsatisfied with PPIs, and/or complaining of persistent GERD symptoms despite PPI use.

Official Title
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A Pilot Study to Evaluate the Feasibility and the Safety of an Endoluminal-suturing Device (Endoimna) as a Treatment of GERD.

Conditions
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GERD

Intervention / Treatment
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* Device: Endomina


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: 1. Subject is 21 - 70 years of age at the time of informed consent 2. Subject has documented symptoms of GERD (heartburn and/or regurgitation) for longer than 12 months, which respond at least partially to proton pump inhibitors (PPIs) 3. Subject is under continuous PPI therapy for at least 6 months 4. Subject has a diagnosis of GERD based on at least 2 of the following criteria: Past demonstration of reflux esophagitis grade A, B or C (LA classification) Abnormal esophageal acid exposure during esophageal pH-impedance monitoring (defined as distal esophageal pH < 4 for > 4 % of the monitoring time) performed after at least 7 days off of PPIs Positive symptom association between GERD symptoms and reflux episodes (symptom association probability ≥ 95%) demonstrated at pH-impedance monitoring) Exclusion Criteria: Subjects who meet any of the following exclusion criteria cannot be enrolled in the study: Subject underwent previous surgery involving the gastroesophageal junction, such as a Nissen fundoplication Subject underwent previous endoscopic intervention for the treatment of GERD and/or Barrett's esophagus Subject has a hiatal hernia larger than 3 cm as determined by endoscopy Subject has history of gastroparesis Subject has any non-GERD esophageal motility disorders that in the opinion of investigator precludes an anti-reflux procedure Subject has history of or known esophageal stricture or significant esophageal anatomic abnormalities (obstructive lesions, etc.) Subject has Barrett's epithelium or any grade of dysplasia Subject has documented history of esophagitis Grade D (LA Classification) Subject has a history of suspected or confirmed esophageal or gastric cancer Subject has esophageal or gastric varices Subject has symptoms of dysphagia more than once per week every week within the last 3 months Subject is unable to tolerate withdrawal from PPI medications Subject has a body mass index (BMI) > 35 kg/m2 Subject has any significant multisystem diseases Subject has an autoimmune or a connective tissue disorder (scleroderma, dematomyositis, Calcinosis-Raynaud's-Esophagus Sclerodactyly Syndrome (CREST), Sjogren's Syndrome, Sharp's Syndrome, etc.) requiring therapy in the preceding 2 years Subject has 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 Subject has had a significant cerebrovascular event within the last 6 months 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 Subject has an active infection as determined by the investigator Subject has a history of any malignancy in the last 2 years Subject has a life expectancy less than 3 years Subject has a diagnosed major psychiatric disorder (bipolar, schizophrenia, etc.) Subject has any condition that, at the discretion of the investigator or sponsor, would interfere with accurate interpretation of the study endpoints or preclude participation in the trial Subject has a diagnosis of eosinophilic esophagitis

Ages Eligible for Study
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Minimum Age: 21 Years
Maximum Age: 70 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
Intervention Model: Single Group Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Intervention<br>The procedure will be performed under general anesthesia with tracheal intubation. Endomina will be introduced into the stomach over a guidewire and then fixed to the endoscope. The procedure will include at least one suture of the gastric cardia to tighten it. Patients will be kept overnight after the procedure. | Device: Endomina<br>* The procedure will be performed under general anesthesia with tracheal intubation. Endomina will be introduced into the stomach over a guidewire and then fixed to the endoscope. The procedure will include at least one suture of the gastric cardia to tighten it. Patients will be kept overnight after the procedure.<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| number of sutures at endoscopy (feasibility) | persistence of sutures at endoscopy | 12 months follow-up | 
| Incidence of all Adverse Device Effects | Safety will be characterized by the incidence of all Adverse Device Effects | 12 months follow-up | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Assessment of Reflux (1) | Change from baseline to the 6-month follow-up visit of the mean percentage (%) of time distal esophageal pH is <4.0 using Esophageal Impedance-pH Monitoring performed of at least 7 days off PPIs and at least 2 days off H2 blocker | 6 month follow-up | 
| Assessment of Reflux (2) | Change from baseline to the 6-month follow-up visit of the total number of reflux episodes, proximal reflux episodes and DeMeester score using Esophageal Impedance-pH Monitoring | 6 month follow-up | 
| Evaluation of Esogastric junction | Change from baseline to the 6-month follow-up visit of the basal LES pressure and IRP4s using High resolution esophageal manometry | 6 month follow-up | 
| Gastro-esophageal reflux disease health-related quality of life score (GERD-HRQL score) | Change from baseline to the 3, 6 and 12 months follow-up visit of the mean GERD-HRQL score. GERD-HRQL score has 13 items, which focus on heartburn symptoms, dysphagia, regurgitations, medication effects and the patient's present health condition. Each item is scored from 0 to 5, with a lower score indicating a better quality of life. | Baseline 3, 6 and 12 month follow-up | 
| Reflux Symptom Index Score | Change from baseline to the 3, 6 and 12 months follow-up visit of the mean Reflux Symptom Index (RSI) score. Reflux Symptom Index Score is an 9-item index designed to assess laryngo-pharyngeal symptoms related to gastro-esophageal reflux. Scores range from 0 to 5, with a higher score indicating more severe symptoms. | Baseline 3, 6 and 12 month follow-up | 
| Mean acid-suppression medication use | Mean acid-suppression (PPI and H2 blocker) medication use at 3, 6 and 12 months follow up. | Baseline 3, 6 and 12 month follow-up | 
| Mean quality of life change | Change from baseline to the 6 and 12 months follow-up visit of the Mean Quality of life scores as measured by SF-12. Twelve-Item Short-Form Health Survey (SF-12) is a multipurpose short form survey with 12 questions measuring physical functioning, role limitations due to physical health problems, bodily pain, general health, vitality (energy/fatigue), social functioning, role limitations due to emotional problems, and mental health (psychological distress and well being). Norm-based scoring (NBS) linearly transforms the scales and summary measures to have a mean of 50 and standard deviation of 10 based on US general population data, so that a higher score indicates a better health state. | Baseline, 6 and 12 month follow-up | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Endoscopy, Mini invasive