Research Project
9031146
? DESCRIPTION (provided by applicant): The purpose of the proposed work is the development of a nearly painless implantable cardioverter defibrillator (ICD). Sudden cardiac arrest (SCA) remains the number one killer in western civilization. The underlying mechanism of SCA is usually ventricular fibrillation (VF), and survival depends on prompt defibrillation. Existig defibrillators rely on the delivery of a brief high voltage shock to the heart. While this is life-saving, the shock is extremely painful when delivered to a conscious patient, as typically happens when the therapy is provided by an ICD. The pain caused by standard ICD shocks is due to the abrupt contraction of skeletal muscles of the chest and abdomen when the shock is applied to the heart. Our team has developed a novel means to accomplish painless defibrillation using a burst of ramped high frequency alternating current (rHFAC) to tetanize skeletal muscle so it does not further contract when a defibrillatory shock is then applied. We have already proven substantial reduction in skeletal muscle activation in animals defibrillated using this technology, and therefore believe that delivery of this novel therapy by an ICD will be a far less painful alternative to standard defibrillation shocks. The goals of the current Direct-o-Phase II proposal are focused on development of human grade hardware, optimization of the therapy, proof of efficacy and safety in GLP animal studies, and submission of an IDE application to the FDA to enable first-in-man studies planned for Phase IIb. We will design, build, and test a new system to deliver the novel therapy, making sure it meets all electrical and mechanical standards for human use. While this system will be an external apparatus, it will allow us to prove the value of the novel therapy in animals and humans, and therefore pave the way for subsequent development of the technology in a fully implantable device. Animal studies will be performed both to determine optimal waveform parameters to reduce skeletal muscle activation and to demonstrate absence of untoward electrical and biological effects using the human grade system. Data collected during device testing and animal studies will be submitted in the IDE application. Once approved for human use by the FDA, we will pursue IRB approval to initiate human investigation in the next phase of the work.
