The purpose of this STTR project is to perform three key tasks essential to the ultimate FDA approval and commercialization of a new minimally invasive treatment for epilepsy, Trigeminal Nerve Stimulation. Epilepsy is a chronic condition characterized by recurrent seizures, and affects over three million Americans. One million (30 percent) have poorly controlled epilepsy. Poorly controlled epilepsy is disabling, and leads to unemployment, recurrent injury, and a high risk of death. Interest is growing in neuromodulation for epilepsy, including vagus nerve stimulation, deep brain stimulation, or closed-loop ""responsive"" neurostimulation as alternatives to failed drug therapy. These approaches are expensive, invasive, and have only modest efficacy. Trigeminal Nerve Stimulation (TNS) is an emerging neuromodulation therapy, which has unique advantages. Unlike VNS, TNS can be delivered non-invasively, bilaterally, and at low cost. Its use in drug resistant epilepsy was pioneered at UCLA, where the results of pilot clinical trials show it to have a robust effect. The trigeminal nerve is the largest cranial nerve, with three pairs of afferent cutaneous branches located over the face. These branches have extensive connections with brain structures known to play a role in seizure inhibition and initiation (locus coeruleus, thalamus, and cerebral cortex). The superficial location of these branches makes the trigeminal nerve a unique vehicle to deliver neurostimulation safely and externally. Data from animals and our pilot clinical trials indicate that TNS has a strong anti-epileptic effect, with a responder rate (>50 percent reduction in seizures) of >40 percent at 6 and 12 months. We are developing both external and subcutaneous TNS, and the external device is closest to a pivotal trial. Before the pivotal trial, there is a need to optimize the electrodes used to minimize skin irritation, a common side effect when used for more than 12 hours per day. In addition, we need to design and engineer a new programmable pulse generator to ensure safe stimulation at much lower currents than existing external stimulators. Further we need to test the new pulse generator and electrode design in healthy subjects and people with epilepsy. We propose a two-year, Phase I STTR to perform the following three key tasks. Completing these tasks will be essential in moving TNS toward a large pivotal trial and ultimate FDA approval. 1. Evaluate the effects of a series of stimulation parameters and electrode gels in an ISO compliant skin irritation model in rabbits for optimal tolerability of the system for patients. 2. Design and Engineer a new external pulse generator in preparation for the pivotal study and PMA submission. 3. Human Feasibility Study: Conduct a human feasibility study to test the new pulse generator and optimized electrodes in healthy subjects and people with epilepsy.
Public Health Relevance: Epilepsy affects over three million Americans, of which one million (30 percent) have seizures that are not controllable with medications. There is growing interest in new forms of treatment for epilepsy, such as neurostimulation, as an alternative to failed drug therapy or surgery. Trigeminal Nerve Stimulation (TNS) is an emerging neurostimulation therapy, which has unique advantages over drugs and other brain stimulation therapies. It is low cost, does not require surgery, and has fewer side effects than drugs for epilepsy. We propose three tasks, which are needed to move TNS closer to FDA approval as a new treatment for people with epilepsy. A new non-invasive, low cost treatment for people with epilepsy would be a major advance for the millions with epilepsy worldwide.
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