Gastroesophageal reflux disease (GERD) affects 8-33% of the global population. GERD can lead to esophagitis, strictures,ulcerations and Barrett's esophagus (BE). Patients with BE have up to an 125-fold increased risk of developing esophagealadenocarcinoma-a devastating outcome which is fatal in roughly 80-90% of cases. Currently, the gold standard treatmentfor GERD remains long-term proton pump inhibitors, i.e. PPI therapy, or laparoscopic Nissen fundoplication (LNF).However, PPI therapy fails to control GERD symptoms in 25%-42% of patients, and the chronic use of PPIs is associatedwith serious adverse effects. Moreover,LNF is technically exacting, and currently fewer than 1% of the eligible GERDpopulation pursue surgery due to concerns of postoperative complications and surgical failure. Thus, an alternative surgicaltreatment is needed to close the "therapy gap". Recently, LINX magnetic sphincter augmentation surgery (MSA) has becomean alternative surgical option to address the therapy gap (FDA-approved, January, 2012; Torax Medical, MN), The LINXdevice is a ring of magnets permanently placed laparoscopically around the gastroesophageal junction (GEJ). Although theside-effect profile of MSA is somewhat superior to LNF, unfortunately,high rates of postoperative dysphagiaare routinelyseen after LINX placement along with low rates of device erosion.To address these issues and improve GERD therapy, we have developed an entirely new class of GERD treatment: a novelbiodegradable device. Our device is called the Eschara suture collar and consists of a dense, tubular matrix of bioabsorbablesuture material that will create a ring of collagen around the lower esophageal sphincter, in the region of the GEJ. As thematerial biodegrades within a matter of days, it loses tensile strength, thus avoiding any dysphagia. Within a matter ofweeks, the suture collar material totally absorbs and, via a foreign body reaction, leaves behind a collar of collagen thatsupplies the appropriate amount of LES augmentation to demonstrably improve LES effacement characteristics, increaseyield pressure, decrease compliance at the GEJ, and increase functional LES length, thereby preventing pathologic acidreflux. We developed the Eschara device in order to provide an ideal GERD solution with the following advantages overLNF and LINX: 1) Correct GERD pathophysiology, 2) preserve natural physiological swallowing, belching, and vomiting,minimize dysphagia, 3) cause minimal risk to the vagus nerve, 4) no risk of erosion, 5) MRI, and all imaging, compatible,6) simple manufacturing, 7) Enable simplified Hiatal Hernia repair, and 8) eliminate the need for continued PPI use.To ensure adequate performance of the Eschara suture collar prototype, we will 1) fabricate and develop the design; then 2)test and validate it in an in vivo swine model. Based on the results of initial experiments, we will: 3) Fabricate and developthe second round of design iteration; 4) perform second swine experiment. This Phase 1 SBIR proposal prepares us for anSBIR Phase II grant aimed at achieving design freeze, regulatory preparation, and commercialization. Also, we will criticallyevaluate our suture model to determine whether the Eschara technology could efficiently meet the needs of the GERDmarket and be a successful alternative to current surgical techniques, leading to improved care for GERD patients.
Public Health Relevance Statement: PROJECT NARRATIVE
There is currently no ideal minimally invasive surgery for patients with gastroesophageal reflux failing medical
management, and current surgical approaches are either physiologically and anatomically disruptive (Nissen
fundoplication) or require a permanent foreign body implant around the gastroesophageal junction (LINX magnetic
augmentation). In this Phase 1 SBIR program, we will develop and validate a novel biodegradable suture collar device
(Eschara Medical) to be positioned around the gastroesophageal junction, ultimately resulting in uniform collagen
deposition that will augment the lower esophageal sphincter, and favorably affect yield pressure and compliance
dynamics at the gastroesophageal junction. This will provide the GERD therapy community a safe and effective tool to
enhance the GERD treatment armamentarium.
Project Terms: Achievement ; Achievement Attainment ; Affect ; Anatomy ; Anatomic ; Anatomic Sites ; Anatomic structures ; Anatomical Sciences ; Animals ; Barrett Esophagus ; Barrett Syndrome ; Barrett Ulcer ; Columnar Epithelial-Lined Lower Esophagus ; Columnar-Lined Esophagus ; esophageal intestinal metaplasia ; Clinical Trials ; Collagen ; Communities ; Deglutition ; Swallowing ; Deglutition Disorders ; Dysphagia ; Swallowing Disorders ; Pharmaceutical Preparations ; Drugs ; Medication ; Pharmaceutic Preparations ; drug/agent ; Engineering ; Eructation ; Belching ; Esophagitis ; Esophagogastric Junction ; Gastroesophageal Junction ; esophagogastric sphincter ; Esophagus ; Feasibility Studies ; Fibrosis ; Flatulence ; Flatus ; Food ; Food or Food Product ; Foreign Bodies ; Foreign-Body Reaction ; Freezing ; Gases ; Gastroenterology ; Gastroesophageal reflux disease ; Acid Reflux ; Esophageal Reflux ; GERD ; Gastro-oesophageal Reflux ; Gastroesophageal Reflux ; Patient Care ; Patient Care Delivery ; Goals ; Gold ; Grant ; Health ; Hernia ; Hiatal Hernia ; Lead ; Pb element ; heavy metal Pb ; heavy metal lead ; Magnetic Resonance Imaging ; MR Imaging ; MR Tomography ; MRI ; Medical Imaging, Magnetic Resonance / Nuclear Magnetic Resonance ; NMR Imaging ; NMR Tomography ; Nuclear Magnetic Resonance Imaging ; Zeugmatography ; Patients ; Postoperative Complications ; post-operative complications ; Postoperative Period ; Post-Operative ; Postoperative ; pressure ; Relaxation ; Repeat Surgery ; Reoperation ; Risk ; Stomach ; gastric ; Surgical sutures ; Sutures ; Family suidae ; Pigs ; Suidae ; Swine ; porcine ; suid ; Technology ; Tensile Strength ; Testing ; Time ; Tissues ; Body Tissues ; Ulcer ; Ulceration ; Vagus nerve structure ; Cranial Nerve X ; Pneumogastric Nerve ; Tenth Cranial Nerve ; Vagus Nerve ; Vomiting ; Emesis ; Measures ; falls ; Device Designs ; Recrudescences ; Caring ; nerve injury ; neural injury ; base ; improved ; Procedures ; Fundoplication ; Nissen Operation ; Chronic ; Clinical ; premature ; prematurity ; repaired ; repair ; Phase ; Histologic ; Histologically ; Physiological ; Physiologic ; Medical ; Ensure ; Inferior esophageal sphincter structure ; Lower Esophageal Sphincter ; cardiac sphincter ; Failure ; Reflux ; Functional disorder ; Dysfunction ; Physiopathology ; pathophysiology ; Esophageal Adenocarcinoma ; Adenocarcinoma of the Esophagus ; Tubular ; Tubular formation ; Deposit ; Deposition ; tool ; Nature ; Proton Pump Inhibitors ; programs ; Scanning ; Techniques ; Location ; Operative Procedures ; Surgical ; Surgical Interventions ; Surgical Procedure ; surgery ; Operative Surgical Procedures ; magnetic ; Magnetism ; experience ; Performance ; success ; novel ; Devices ; Position ; Positioning Attribute ; Device Removal ; Modeling ; response ; Adverse Experience ; Adverse event ; Adverse effects ; preventing ; prevent ; Sphincter ; Address ; Length ; Symptoms ; in vivo ; Small Business Innovation Research Grant ; SBIR ; Small Business Innovation Research ; Validation ; Pathologic ; Preparation ; Characteristics ; Development ; developmental ; Image ; imaging ; community intervention ; design ; designing ; Outcome ; Population ; migration ; innovation ; innovate ; innovative ; Implant ; prototype ; commercialization ; FDA approved ; minimally invasive ; standard care ; standard treatment ; minimal risk ; reduce symptoms ; alleviate symptom ; ameliorating symptom ; decrease symptom ; fewer symptoms ; relieves symptoms ; symptom alleviation ; symptom reduction ; symptom relief ; experimental study ; experiment ; experimental research ; Life Style Modification ; lifestyle modification ; preservation ; in vivo evaluation ; in vivo testing ; side effect ; porcine model ; pig model ; piglet model ; swine model ;
