Development of a closed-loop, implantable, electroceutical device for gastric disorders

Gastroparesis and functional dyspepsia are debilitating stomach disorders that together affect 10% of the world population. Modulating gastric function is an important target function for alternative therapies like gastric electrical stimulation (GES). The Enterra device is the only FDA approved implantable device currently available that can administer GES to entrain gastric slow wave activity. However, recent evidence has called into question the clinical utility of this system. In this work, I present the development and in vivo application of a new, closed loop, chronically implantable electroceutical device capable of continuously recording gastric motility and administering synchronous GES, that will form the needed foundation for neuromodulation protocols that can correct shortcomings in past, first-generation bioelectronic attempts to ameliorate and monitor gastric disorders. This system captures gastric serosal myoelectric activity using electrogastrography, as well as gastric contraction activity using strain gauge force transducers. I present data captured from anesthetized and freely behaving rats, demonstrating the ability of the device to capture physiologically relevant gastric motility patterns and changes, safely and effectively. I present a framework built on continuous wavelet transforms to analyze frequency and amplitude changes in captured data to inform potential therapies. I present data demonstrating the ability of the device to selectively stimulate enteric neurons in sync with gastric slow waves, resulting in a relaxation of the pyloric sphincter muscle, in a closed loop fashion. I present the development of a large animal preclinical proof-of-principle version of this system, and data captured from its implantation in freely behaving pigs, as a translational step to future human trials. In the future, this system will enable further studies into future closed loop therapies aimed at increasing gastric accommodation, stimulating physiological gastric emptying and/or pyloric opening with physiologically appropriate timing and extent.