A Pilot Study to Evaluate the Feasibility and the Safety of an Endoluminal-suturing Device (Endoimna) as a Treatment of GERD.
Trial Snapshot
- Phase
- Not Applicable
- Sponsor
- Enrollment
- 15
- Locations
- 2
- Primary Endpoint
- Incidence of all Adverse Device Effects
Study Overview
Brief Summary
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
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.
Study Design
- Study Type
- Interventional
- Allocation
- Na
- Intervention Model
- Single Group
- Primary Purpose
- Treatment
- Masking
- None
Eligibility Criteria
- Ages
- 21 Years to 70 Years (Adult, Older Adult)
- Sex
- All
- Accepts Healthy Volunteers
- No
Inclusion Criteria
- •1. Subject is 21 - 70 years of age at the time of informed consent
- •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)
- •Subject is under continuous PPI therapy for at least 6 months
- •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
Outcomes
Primary Outcomes
Incidence of all Adverse Device Effects
Time Frame: 12 months follow-up
Safety will be characterized by the incidence of all Adverse Device Effects
number of sutures at endoscopy (feasibility)
Time Frame: 12 months follow-up
persistence of sutures at endoscopy
Secondary Outcomes
- Assessment of Reflux (1)(6 month follow-up)
- Assessment of Reflux (2)(6 month follow-up)
- Evaluation of Esogastric junction(6 month follow-up)
- Gastro-esophageal reflux disease health-related quality of life score (GERD-HRQL score)(Baseline 3, 6 and 12 month follow-up)
- Reflux Symptom Index Score(Baseline 3, 6 and 12 month follow-up)
- Mean acid-suppression medication use(Baseline 3, 6 and 12 month follow-up)
- Mean quality of life change(Baseline, 6 and 12 month follow-up)