The purpose of the proposed work is the development of a human-grade system for the prevention of recurrent syncope through neurostimulation of the thoracic nerves controlling the splanchnic venous reservoir. Recurrent syncope, specifically neurally mediated syncope (NMS), is major public health problem affecting as many as 3 million people in the United States alone. Syncope results in significant morbidity and hospitalization due to falls or accidents that occur as a result of frequent failing. These frequent physical complications result in prolonged inability to work, inability to drive, and recurrent hospitalizations. In the United States an estimated $2 billion is spent annually on patient hospitalized for syncope. There are few treatments that work for patients with NMS. Coridea has developed a novel approach for treating syncope by the mobilization of blood from the splanchnic reservoir to the central circulation by means of stimulation of the greater splanchnic nerve (GSN). We have already developed a prototype cuff and stimulation system and tested them in large animals. This work demonstrated the feasibility and safety of intermittent GSN stimulation as well as the desired changes in physiological measures of improved central flow (increased flow in the inferior vena cava, increased central venous pressure, increased preload, etc.). We therefore believe that stimulation of the GSN in patients with NMS can be carried out safely and will lead to prevention of syncope and ultimately reduced re-hospitalization and improved patient morbidity. The goals of this Direct-to-Phase II proposal are focused on the optimization of device design to allow for minimally invasive placement of the neurostimulation cuff and the parameters for safe and effective neurostimulation, which will be demonstrated in animal studies. The system will be designed to conform to safety regulations. We believe that there will be sufficient evidence at the end of this Phase II SBIR to support an investigational device exemption (IDE) application to the Federal Drug Administration (FDA) for the first-in-human studies planned for Phase IIb. We will engage with established contract manufacturing groups with experience in electrode cuff design and translation of engineering concepts to the clinic. The implantable neurostimulation system will be engineered under the contract manufacturers? design control system, ultimately enabling us to prove the value of the novel therapy in humans. Animal studies will be performed to optimize the treatment parameters, evaluate system usability and demonstrate absence of untoward biological effects using in a safety study conforming to the standards of good laboratory practices (GLP). Data collected during device testing and GLP animal studies will be submitted to the FDA in the next phase of the work.
The goal of the proposed work is the development of a neurostimulation system to induce temporary constriction of the splanchnic venous reservoir in order to maintain blood pressure and mitigate syncope. This novel approach will provide a therapeutic option for patients suffering from recurrent syncope. The work in this Direct-to-Phase II application will support complete safety testing of the human-grade neurostimulation system to enable subsequent first- in-man investigation.
