High resolution, noninvasive measurement and functional classification of vagal nerve response patterns in relation to gastroparesis symptom management using gastric electrical stimulation therapy

Gastroparesis (GP) is a common chronic disorder in which gastric emptying is delayed in the absence of an anatomical obstruction, leading to frequent postprandial distress, nausea and vomiting. Almost all patients with GP (>90%) experience nausea after a meal. Pharmaceutical treatments are ineffective or dangerous and simple dietary modification has minimal benefit. Because of the lack of effective drug treatment, many patients are implanted with a gastric electrical stimulation (GES) system as a last-resort effort to help manage their symptoms. Gastric electrical stimulation has been shown to be a moderately effective treatment of nausea and vomiting in patients with GP. However, how GES works is unclear, as patients who undergo GES show resolution of nausea and vomiting before any improvement in gastric emptying is recognized. Since GES does not modify gastric emptying but does improve symptoms, the mechanism-of-action for symptom relief is likely vagal. Our preliminary work strongly supported this hypothesis, which formed the foundation for our SPARC3 project. In this unique, multidisciplinary academic-clinical-industry collaboration, whose members include two of the world’s most respected authorities on the vagal-gut connectome, Dr. Terry Powley and Dr. John Furness, we (project Leads Ward, Nowak, Everett and Clements) will perform a series of noninvasive clinical studies with GP patients receiving GES therapy to further characterize the role of the vagus in GP symptom management and to determine whether vagal response feedback-mediated optimization of stimulus delivery leads to predictable improvements in vomiting, nausea and other troubling symptoms of GP. We will use state-of-the-art, multichannel cutaneous electrode arrays from BioCircuit Technologies, signal processing strategies from Purdue and IUSM, and experience from studies performed with Dr. Powley’s group to 1) fill a critical knowledge gap in GES literature by describing the role of the vagal nerves in mediating the anti-emetic effects of GES, 2) further define the variable anatomical course of the cervical vagus between patients through the use of BioCircuit’s noninvasive, functional nerve response imaging technology, 3) identify the direction(s) of GES-evoked CNAP conduction (e.g., to identify if GES evokes a vago-vagal reflex, which would have an efferent component, or whether the measured response is purely afferent/sensory), 4) describe the nature of vagal nerve conduction changes secondary to diabetic neuropathy, and 5) define a set of exemplar vagal nerve response signature(s) of effective and ineffective GES.