Novel Evaluation & Treatment of Gastric Dysmotility

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Gastric dysmotility is relevant in several clinical disorders including gastroparesis and functional dyspepsia. This grant reflects the Pi's long-term research objectives to advance the evaluation and treatment of gastric motility disorders through a better understanding of the regulatory factors involved in gastric motility. The first overall aim is to further develop and validate noninvasive, quantitative tests for clinical evaluation of gastric motility. These include electrogastrography, a scintigraphic test to simultaneously assess gastric emptying and volume, and a capsule that records both pH and pressure to provide an assessment of gastric residence time and contractility. The second overall aim is to investigate novel treatments for improving patients' symptoms and gastric motility. Importantly, each of these patient- oriented research projects will entail close interaction between the PI and beginning clinical investigators to mentor them through instruction, guidance, and encouragement to develop their clinical research skills. The specific aims for this renewal of the Pi's NIH K24 Patient-Oriented Research Award are: 1. To develop several novel techniques for assessing gastric motility in evaluating patients with suspected abnormalities and/or symptoms of gastric motor function: a) a capsule to record simultaneous pH and contractility throughout the gastrointestinal tract; b) electrogastrography (EGG) and water load testing; c) combined gastric emptying and gastric volume measurement in a single scintigraphic-SPECT test. 2. To test novel treatments for symptomatic gastric motility disorders: a) the phosphodiesterase type 5 inhibitor, sildenafil; b) the tricyclic antidepressants, amitriptyline and desipramine. 3. To explore the temporal relationship between fasting (phase I, II, III)and postprandial motility patterns and the plasma concentration of several putative regulatory hormones of Gl motility (motilin and pancreatic polypeptide) and appetite (ghrelin, leptin) in normal subjects and patients with gastroparesis. 4. To enable the principal investigator to expand his mentoring activities for beginning clinical investigators in patient-oriented, Gl motility research. An organized approach to teach clinical research will include didactic sessions, organized Gl motility research conferences, weekly research working meetings, and hands on supervision of individual research projects.