Exploration of Subtypes of Gastroparesis and Gastroparesis-like Symptoms based on Physiological Testing

项目摘要 该项目包括继续目前由NIDDK胃轻瘫进行的研究 临床研究联盟（GpCRC）和该研究中心提出的一项新方案， 由财团执行。GpCRC的使命是提高对 发病机制、病因学和与GP相关的症状的治疗。提高精度， GP患者和GP患者需要诊断和治疗方法， 类似于正常胃排空的症状，这种疾病称为功能性消化不良或FD， 项目因此，我们的目标是：1）继续第三次资助中开始的重要研究 阶段（胃轻瘫登记3或GpR 3）; 2）通过测量 胃肌电活动（GMA），胃调节和敏感性，胃窦幽门 探讨球囊扩张幽门的疗效 在减少GP和FD患者的症状方面， 财团GpR 3的研究将在GpR 4中继续并完成，包括：GP登记， 丁螺环酮治疗早饱和胃轻瘫症状：多中心、随机、安慰剂- 对照、双盲试验（BEST），了解胃轻瘫的病理基础 和鉴定参与其发病机制的分子因子（PBG）研究，以及幽门螺杆菌 胃轻瘫症状患者的括约肌关闭（PSAGS）。GP的两种亚型 和基于GMA的FD响应于水负荷饱腹感测试已经被确定：一个与 正常3cpm（GMA）和另一个胃节律紊乱。正常3 cpm GMA对照正常 胃蠕动收缩，需要正常数量的Cajal间质细胞（ICC）。ICCS GP严重耗竭，FD中度耗竭。ICC损失导致3 cpm损失 GMA和胃节律紊乱增加，与胃排空延迟相关， 恶心之类的症状内镜幽门治疗可减轻GP患者的症状，3 cpm GMA，表明幽门流出功能障碍在症状的发生中起作用。我们 假设GP和FD患者的3 cpm正常且幽门扩张性差， 与患者相比， 胃节律紊乱GP（或FD）伴3 cpm GMA或胃节律失常的患者， 在单盲研究中，将对幽门扩张性差的患者进行幽门球囊扩张。 基于GMA识别GP和FD的亚型将有助于提供一种更合理的方法， 选择患者进行幽门治疗并改善治疗结果。

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.