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

项目摘要 该项目包括NIDDK胃轻瘫目前正在进行的研究的继续 临床研究联盟(GpCRC)和该网站提出的一个新方案，将是 由财团进行。GpCRC的使命是增进对 GP相关症状的发病机制、病因和治疗。提高了 对于GP患者和GP患者，需要诊断和治疗方法 类似于胃排空正常的症状，在此称为功能性消化不良或FD 项目。因此，我们的目标是：1)继续在第三次资助中开始的重要研究 阶段(胃轻瘫登记表3或GpR3)；2)通过测量进一步确定GP的主要亚型 胃肌电活动(GMA)、胃调节和敏感性、胃窦-幽门 3)探讨幽门球囊扩张术的疗效 在减轻GP和FD患者症状方面，将由 财团。GpR3中有待继续并在GPR4中完成的研究包括：全科医生登记处， 丁螺环酮治疗早饱和胃瘫症状：一种多中心、随机、安慰剂 对照双掩蔽试验(BESST)，了解胃瘫的病理基础 和参与其发病机制(PBG)研究的分子因素的鉴定以及幽门螺杆菌 胃瘫症状(PSAGS)患者的括约肌异常。GP的两个亚型 和基于GMA的FD对水负荷饱和测试的响应已经被识别：一种 正常3cpm(GMA)1例，胃电节律紊乱1例。正常3 CPM GMA控制正常 胃蠕动收缩，需要正常数量的Cajal间质细胞(ICCs)。ICCS 在GP中严重消耗，在FD中适度消耗。ICC损失导致3CPM损失 GMA和增加的胃电节律紊乱与胃排空延迟和 恶心等症状。胃镜下幽门螺杆菌治疗可减轻GP和3 CPM GMA，提示幽门流出功能障碍在症状的发生中起一定作用。我们的 假设GP和FD患者的3cpm正常，幽门扩张性差 与患者相比，气囊扩张幽门后症状的减轻程度更大。 伴有胃电节律紊乱。GP(或FD)合并3CPM GMA或胃电节律紊乱的患者 幽门扩张性差的患者将在一项单盲研究中接受幽门气囊扩张。 基于GMA的GP和FD亚型识别将有助于提供更合理的方法 选择患者进行幽门治疗，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.