Definitive Evaluation of Gastric Dysrhythmia as a Disease Mechanism by a Novel Body Surface Gastric Mapping Technique

Functional dyspepsia and chronic nausea and vomiting syndromes affect >10% of the population, inducing a vast burden of ill-health and economic harm. Yet despite their enormous impact, these diseases remain poorly understood, with few objective diagnostic tests available to subtype patients and direct therapies. There is a pressing need for new mechanistic insights and diagnostic solutions that can better characterize these common and burdensome disorders. In this proposal, we translate and apply a new diagnostic approach with outstanding potential to define mechanims of gastric dysfunction - ‘Body Surface Gastric Mapping (BSGM)’. BSGM has been pioneered by our team, and represents the first accurate non-invasive tool for detecting and mapping spatial patterns of gastric electrical activity. In this project, we will apply BSGM to definitively resolve whether gastric dysrhythmias are an important mechanism of gastric dysfunction. Although this hypothesis is longstanding, it has never been adequately investigated because past clinical methods (electrogastrography; EGG) were inaccurate due to their technical limitations and their focus on frequency. Our preliminary BSGM data is revealing new sensitive and specific spatial biomarkers of gastric dysfunction, which correlate well with symptoms, and which were not addressable using previous EGG metrics such as frequency. Several innovations have converged to now enable the translation of BSGM in large clinical studies: flexible arrays of 8x8 cutaneous electrodes, a custom-built multichannel data-logger, a symptom-tracking App coupled to the data-logger by Bluetooth, and a sophisticated analysis pipeline to accurately map the retrieved signals. These BSGM innovations will be applied to definitively evaluate the clinical significance of gastric dysrhythmias with reference to an expert consensus guideline: ‘Plausibility Criteria for Putative Mechanisms of GI Functional Disorders’. This guideline identifies 5 specific criteria that must be met to validate new functional disorder mechanisms, and these criteria therefore also define our 5 Specific Aims: 1. Defining the presence of gastric dysrhythmia in a subset of patients with symptoms of gastric dysfunction; ii) Defining a temporal association between gastric dysrhythmia and symptoms; iii) Correlation with symptom severity; iv) Induction of gastric dysrhythmia with symptom onset in healthy controls; and v) A congruent natural history. These aims will be addressed by building and applying BSGM devices in non-invasive studies of 400 patients and 200 controls. The studies will be performed at two leading US motility centers of excellence, backed by an interdisciplinary team of clinicians and bioengineers who share an outstanding track record for innovation and translation. This project is anticipated to yield 3 high-impact outcomes, each of which would be a breakthrough advance in the GI motility field: i) A definitive answer to the longstanding question of whether gastric dysrhythmias are clinically important; ii) Presenting BSGM as a new clinical diagnostic tool for gastric dysfunction; and iii) Validation of novel biomarkers and therapeutic targets through BSGM to guide future interventions.