SBIR-STTR Award

The ultimate goal of this project is to develop a simple laparoscopic product (Partial Cuff) to treat gastroesophageal reflux disease (GERD) or acid reflux. Of the 40 million U.S. GERD sufferers currently manage their symptoms by life-time medications, at least 4.5 million will require additional or alternative remedies, while another 4 million are not satisfied with their medication regimen. Though fundoplication surgery is the only cure, its severity, risks and physiological perturbations are barriers to adoption by over 99% of patients. GERD represents the most expensive of all of the GI diseases, with over $6 billion spent annually just in prescription medications alone, and this number is growing. Because of the size of this market, many less invasive and mostly trans-oral endoscopic procedures have been developed by large and small companies. They aim to achieve the same objective as surgery in increasing the constraints of the lower esophageal sphincter (LES). Most of these procedures represent significant technical challenges with less than satisfactory clinical outcomes and none of them have been widely adopted. Partial Cuff is designed to be placed laparoscopically, simply and directly onto the esophagus with a click of its special placement handle, thereby circumventing the cumbersome surgery of wrapping a segment of the stomach over the esophagus. Once applied, the shaped and flexible Partial Cuff hugs the esophagus and imparts an immediate constraint over a portion of the LES similar to the Toupet partial fundoplication procedure. This allows the unconstrained portion of the LES still be able to open naturally, such as during swallowing or burping. When tissue ingrowth completes in about 8 weeks, the Partial Cuff becomes integral in the LES wall, further imparting its constraining utilit. This simple and direct treatment procedure minimizes challenges plaguing current surgeries and trans- oral procedures. The proposed Partial Cuff is to improve the quality of life and mitigate life-long dependence on medications for millions of GERD sufferers. This in turn will result in a substantial reduction in national healthcare costs. For Phase I, we propose to advance our concept to working devices. They will be tested on a bench top model and in an in vivo pigs study to verify the working hypothesis, assess biocompatibility and whether the device stays in place. Preliminary work has been completed on the anatomy and pathophysiology of the LES including a finite element analysis on an analogous model of urethral incontinence. The three parts of the device system will be engineered, made, assembled and tested as stated above. Completing this Phase I will allow us to further validate this in a clinical feasibility stuy and to fulfill requirements towards FDA allowance in Phase II.

Public Health Relevance Statement:


Public Health Relevance:
Of the 19 million U.S. acid reflux sufferers relying on medication management, over 4.5 million will require additional or alternative remedies. This application describes a simple laparoscopic surgical device that avoids issues associated with other surgeries and trans-oral treatment procedures. Based on the same principle as the successful but complicated fundoplication surgery, this substantially easier and simpler device will benefit patients, surgeons and payers as well as reduce lifetime prescription medication costs for the increasing number of acid reflux sufferers.

Project Terms:
Acids; Adopted; Adoption; Adverse effects; Adverse event; Affect; Anatomy; Animals; Autopsy; base; biomaterial compatibility; Caliber; Clinical; Contracts; cost; Country; Deglutition; Dependence; design; Development; Devices; Disease; Engineering; ergonomics; Esophagus; Evaluation; Family suidae; Finite Element Analysis; flexibility; Functional disorder; Fundoplication; Gastroesophageal reflux disease; Gastrointestinal Diseases; Glues; Goals; Government; Health Care Costs; Histocompatibility; Human; Implant; implantable device; improved; in vivo; Incontinence; Inferior esophageal sphincter structure; Life; Marketing; Measurement; Measures; Medication Management; meetings; Modeling; nitinol; Operative Surgical Procedures; Oral; Organ; Outcome; Patients; Persons; Pharmaceutical Preparations; Phase; Physiological; Plague; Polypropylenes; pressure; Procedures; prototype; public health relevance; Quality of life; Reflux; Regimen; repaired; Resources; Risk; Sampling; Severities; Shapes; Silicones; Simulate; Small Business Innovation Research Grant; Sphincter; Sterility; Stomach; success; Surgeon; Symptoms; System; Testing; Time; Tissues; Urethra; Vendor; Vision; Work

The ultimate goal of this project is to develop a simple product, Partial Cuff (PC), to treat gastroesophageal reflux disease (GERD or acid reflux). Of the 40 million U.S. GERD sufferers managing their symptoms by life- time medications, 5 million will require treatments due to failure of their prescriptive medications. The revelation of significant side effects from long term Proton Pump Inhibitors (PPIs) usage will drive the remaining 35 million on prescription or over the counter PPIs to receive treatment. GERD is the most expensive of all of the GI diseases, with an annual healthcare cost >$10 billion. Due to its severity, risks and physiological perturbations, fundoplication surgery treats <1% of patients. The large and growing number of GERD patients drove the development of many alternative procedures. However, with significant technical challenges and less than satisfactory clinical outcomes, none of them has been widely adopted. PC emulates the proven partial fundoplication but is significantly simpler, easier and safer. It is to be placed laparoscopically, simply and directly onto the esophagus avoiding the cumbersome lifting and wrapping of a segment of the stomach over the esophagus. PC works with body's natural physiology to minimize adverse events common to all other surgical treatments for GERD. PC is designed to improve the quality of life and to mitigate life-long dependence on medications for millions of GERD sufferers. This in turn will result in a substantial reduction in national healthcare costs. Phase I device feasibility goals were successfully met: functional devices were made and implanted over the LES in pigs. Its flexibility and widening with food passage were visualized in vivo through fluoroscopy. Pigs continued to behave and gained weight normally. A special device design feature was developed that allows material to pass easier toward the stomach and not in reverse, and it also eliminates the need for a special device deployment tool. For Phase II, we propose to first refine and finalize the device design and surgical implantation procedure before carrying out a one-year GLP animal study with 24 pigs. Once the device design is finalized and devices made, we will also perform other preclinical tests required by the FDA for an implant device. These tests include the ISO 10993 panel of biocompatibility tests for sterilized devices, fatigue cycling tests to simulate life-time function in patients, an ASTM F2129 metal corrosion test as well a nickel leaching test, all for characterizing the nitinol frame properties. We also propose to build the clinical research study protocol for PC and carry out discussions with the FDA. All these research data results and the clinical study protocol along with the quality system documentation and GMP processes will be in an information package necessary for FDA to grant an IDE clinical study to be carried out in Phase IIB. Commercialization will commence after completion of the clinical study and approval from the FDA to market PC in Phase III.

Public Health Relevance Statement:


Public Health Relevance:
20 of the 40 million U.S. acid reflux sufferers are on prescription medication management, and 5 million of them will require additional or alternative remedies. In this Phase II SBIR, CT Resources plans to expand the successful research from Phase I of a simple laparoscopic surgical device to treat GERD. Based on the same principle as the proven partial fundoplication surgery, this substantially simpler, easier and safer device will benefit patients, surgeons and payers.

Project Terms:
Acids; Acute; Adopted; Adverse effects; Adverse event; Affect; Animal Model; Animals; arm; Authorization documentation; base; biomaterial compatibility; Clinical; Clinical Protocols; Clinical Research; clinical research site; commercialization; Corrosion; cost; cytotoxicity; Data; Dependence; design; Development; Device Designs; Device Safety; Devices; Disease; Documentation; Eating; Esophagus; Evaluation; Failure (biologic function); Family suidae; Fatigue; flexibility; Fluoroscopy; Food; Fundoplication; Gastroesophageal reflux disease; Gastrointestinal Diseases; genotoxicity; Goals; Grant; Healed; healing; Health Care Costs; Histologic; Histology; Human; Implant; implantable device; implantation; Implantation procedure; improved; in vivo; Inferior esophageal sphincter structure; irritation; Life; Lifting; Marketing; Measures; Medication Management; meetings; Metals; migration; Morbidity - disease rate; Nickel; nitinol; Operative Surgical Procedures; Outcome; Patients; Performance; Pharmaceutical Preparations; Phase; phase 1 study; Physiological; Physiology; pre-clinical; Preclinical Testing; Procedures; Process; programs; Property; Protocols documentation; Proton Pump Inhibitors; public health relevance; Quality of life; Reflux; Research; research clinical testing; research study; Resources; response; Risk; Safety; Scanning; Severities; Shapes; Small Business Innovation Research Grant; Stomach; Surgeon; Symptoms; System; Testing; Time; tissue support frame; Tissues; tool; Toxic effect; Weight Gain; Work