Project Summary This project includes the continuation of studies currently conducted by NIDDK Gastroparesis Clinical Research Consortium (GpCRC) and one new protocol proposed by this site that is to be carried out by the Consortium. The mission of the GpCRC is to improve understanding of the pathogenesis, etiology, and treatment of symptoms associated with GP. Improved precision in diagnostic and therapeutic approaches are needed for patients with GP and for patients with GP- like symptoms with normal gastric emptying, a disorder termed functional dyspepsia or FD in this project. Thus, our aims are: 1) to continue the important studies that were begun in the third funding period (Gastroparesis Registry 3 or GpR3); 2) to further define major subtypes of GP by measuring gastric myoelectrical activity (GMA), gastric accommodation and sensitivity, antral – pyloro contractility, and pyloric distensibility; and 3) to explore the efficacy of balloon dilation of the pylorus in reducing symptoms in patients with GP and FD in a new protocol to be carried out by the Consortium. Studies from GpR3 to be continued and completed in GpR4 include: The GP Registry, Buspirone for Early Satiety and Symptoms of Gastroparesis: A Multicenter, Randomized, Placebo- Controlled, Double-Masked Trial (BESST), Understanding the Pathological Basis of Gastroparesis and Identification of the Molecular Factors Involved in its Pathogenesis (PBG) Study, and Pyloric Sphincter Abnormalities in Patients with Gastroparesis Symptoms (PSAGS). Two subtypes of GP and FD based on GMA in response to the water load satiety test have been identified: one with normal 3 cpm (GMA) and the other with gastric dysrhythmias. Normal 3 cpm GMA controls normal gastric peristaltic contractions and requires normal numbers of interstitial cells of Cajal (ICCs). ICCs are severely depleted in GP and modestly depleted in FD. Loss of ICCs results in loss of 3 cpm GMA and increased gastric dysrhythmias which are associated with delays in gastric emptying and symptoms like nausea. Endoscopic pyloric therapies reduce symptoms in patients with GP and 3 cpm GMA, indicating antro-pyloro outflow dysfunction has a role in the genesis of symptoms. Our hypothesis is that patients with GP and FD who have normal 3 cpm and poor pyloric distensibility will have greater reduction in symptoms after balloon dilation of the pylorus compared with patients with gastric dysrhythmias. Patients with GP (or FD) with 3 cpm GMA or gastric dysrhythmias and poor pyloric distensibility will undergo balloon dilation of the pylorus in a single blind study. Identifying subtypes of GP and FD based on GMA will help to provide a more rational approach for selecting patients for pyloric therapy and improving treatment outcomes.