U of L Clinical Center to Investigate the Pathogenesis, Etiology, and Treatment of Gastroparesis through the NIDDK Gastroparesis Consortium

胃轻瘫是一种胃功能障碍，其特征是胃排空延迟，经常与胃排空障碍相关。 慢性恶心呕吐、早饱、餐后饱胀、腹痛和营养不良， 可能需要营养支持。胃轻瘫对生活质量有毁灭性的影响， 影响年轻女性。在过去的5年里，胃轻瘫临床研究联盟（GpCRC） 为提高我们对这种疾病的理解做出了一系列重要贡献（见下文）， 推进患者、医生和NIH管理胃轻瘫的目标。然而， 了解其病因，自然史，治疗策略和临床过程， 这是我们对胃轻瘫联盟的回应背后的基本原理。的最大障碍 有效的治疗方法，胃轻瘫是我们缺乏知识，无论是其发病机制， 其病理生理学。此外，主要症状，如恶心，呕吐，疼痛， 目前测量胃功能（电、运动活动、进餐排空时间）变化的方法很差 最好的最后，我们不了解这些患者的长期结果以及结果是否不同 根据病因、症状严重程度和排空异常程度。因此，我们的方法 对这些患者的治疗是不稳定的，治疗一直是经验性的，只有部分有效，如果有的话，在缓解 主要症状。该委员会的使命完全符合国家人权委员会的建议。 消化疾病委员会：具体而言，研究目标2.6涉及胃轻瘫，并指出： “了解引起恶心和呕吐的有害内脏信号与胃神经电 和/或运动功能障碍以及双向脑肠相互作用。胃轻瘫是典型的 疾病调查。慢性呕吐，一种使人衰弱和社交孤立的消化症状， 在体液和电解质稳态中产生潜在的危及生命的破坏， status.慢性恶心仍然是一种重要的隐性残疾。恶心和呕吐通常同时发生 并与其他GI症状重叠以及在许多消化系统疾病中出现。更有效 恶心和呕吐的治疗将改善生活质量和身体功能， 疾病。关于恶心呕吐相关的外周伤害性信号的研究很少 原发性胃肠道运动/感觉障碍“这项建议的具体目标是：1.完成当前 GpCRC登记处（登记处三）; 2.扩展GpCRC核心实验室，负责解剖学和相关研究 对具有GP综合征的患者的组织样品; 3.对GP患者进行药理学研究 综合症。4.为Gp综合征患者执行新器械/幽门介入研究方案; 和5.利用几种新方法来满足胃轻瘫症状患者的一些未满足的需求， 这可以纳入联合会的新研究。

Gastroparesis is a disorder of gastric function characterized by delay in gastric emptying, frequently associated with chronic nausea and vomiting, early satiety, postprandial fullness, abdominal pain, and malnutrition that may require nutritional support. Gastroparesis has a devastating impact on quality of life and predominantly affects younger women. In the past 5 years, the Gastroparesis Clinical Research Consortium (GpCRC) has made a series of important contributions (see below) to improve our understanding of this disorder and advancing the goals of patients, physicians and the NIH for management of gastroparesis. Yet, much remains to be learned about its etiology, natural history, treatment strategies, and clinical course, which is the rationale behind our response to the Continuation of the Gastroparesis Consortium. The biggest barrier to effective therapeutic approaches to gastroparesis is our lack of knowledge about either its pathogenesis or its pathophysiology. Further, the correlation between the major symptoms such as nausea, vomiting, pain, and current methods to measure change in gastric function (electrical, motor activity, meal emptying times) is poor at best. Finally, we do not understand the long-term outcomes of these patients and whether outcomes differ on the basis of etiology, symptom severity, and degree of emptying abnormalities. Consequently, our approach to these patients is erratic and treatment has been empirical and only partially effective, if at all, in relieving the major symptoms. The mission of the GpCRC is completely aligned with the recommendations of the National Commission on Digestive Diseases: specifically, Research Goal 2.6 relates to gastroparesis and states: "Understand the noxious visceral signaling causing nausea and vomiting related to gastric neuro-electrical and/or motor dysfunction and the bi-directional brain-gut interactions. Gastroparesis provides an archetypal disease for investigative inquiry. Chronic vomiting, a debilitating and socially isolating digestive symptom, creates potentially life-threatening disruptions in fluid and electrolyte homeostasis and compromises nutritional status. Chronic nausea remains a significant hidden disability. Nausea and vomiting usually occur in tandem and overlay with other Gl symptoms as well as presenting in numerous digestive diseases. More effective treatments for nausea and vomiting would improve quality of life and physical functioning in a vast array of illnesses. A paucity of research exists for defining peripheral noxious signaling of nausea and vomiting related to primary Gl motor/sensory disturbances." The Specific Aims of this proposal are to: 1. Complete the current GpCRC registry (Registry Three); 2. Extend the GpCRC core lab, responsible for anatomic and related studies on tissue samples of patients with Gp syndromes; 3. Perform pharmacologic studies on patients with Gp syndromes.; 4. Perform a new device/pyloric intervention study protocol for patients with the Gp syndromes; and 5. Utilize several novel approaches to some of the unmet needs in patients with gastroparesis symptoms, which could be incorporated in new studies of the Consortium.