University of Louisville’s Clinical Center in Gastroparesis Clinical Research Consortium

胃轻瘫是一种以胃排空延迟为特征的胃功能紊乱，常与 慢性恶心和呕吐，早饱，餐后饱腹感，腹痛和营养不良 可能需要营养支持。胃瘫对生活质量有毁灭性的影响，主要是 影响年轻女性。在过去的5年里，胃轻瘫临床研究联盟(GpCRC) 做出了一系列重要的贡献(见下文)，以提高我们对这种疾病的理解和 促进患者、医生和美国国立卫生研究院管理胃瘫的目标。然而，仍然有很多东西 了解其病因、自然病史、治疗策略和临床病程。 是我们对胃瘫联盟RFA-DK-10-502继续作出反应的理由。这个 胃瘫有效治疗方法的最大障碍是我们对其缺乏了解 发病机制或其病理生理学。此外，恶心等主要症状之间的相关性， 呕吐、疼痛和目前测量胃功能(电、运动、进食)变化的方法 清空时间)充其量也是糟糕的。最后，我们不了解这些患者的长期结果， 预后是否因病因、症状严重程度和排空异常程度不同而不同。 因此，我们对这些患者的治疗是不稳定的，治疗一直是经验性的，而且只是部分的。 在缓解主要症状方面有效，如果有的话。GpCRC的使命与 国家消化疾病委员会的建议；5具体而言，研究目标2.6涉及 对于胃瘫和状态：了解引起恶心和呕吐的有害内脏信号与 胃神经电和/或运动功能障碍与脑肠双向相互作用。胃轻瘫 为调查性调查提供了一种典型的疾病。慢性呕吐，一种使人虚弱和社交孤立的症状 消化症状，造成液体和电解质动态平衡的潜在威胁生命的紊乱和 会影响营养状况。慢性恶心仍然是一种严重的隐性残疾。恶心和呕吐 通常相继出现，并与其他Gl症状重叠，并在许多消化系统中出现 疾病。对恶心和呕吐进行更有效的治疗将改善生活质量和身体状况 在一系列疾病中发挥作用。对于外周有害信号的定义还缺乏研究。 恶心和呕吐与初级Gl运动/感觉障碍有关。 这项建议的具体目的是：1.完成现有的GpCRC登记；2.继续GpCRC 核心实验室，负责GP综合征患者组织标本的解剖及相关研究； 继续对GP综合征患者进行药理学研究；4.继续对患有GP综合征的患者进行设备研究 GP综合征；以及5.一项新的多中心研究，基于几项GpCRC辅助研究和其他试点 数据。

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 RFA-DK-10-502. 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;5 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; 2. To continue the GpCRC core lab, responsible for anatomic and related studies on tissue sample of patients with Gp syndromes; 3. Continue pharmacologic studies on patients with Gp syndromes; 4. Continue device studies for patients with the Gp syndromes; and 5. A new multicenter study, based on several GpCRC ancillary studies and other pilot data.