Gastroparesis Clinical Research Consortium-University of Michigan Clinical Center

描述(申请人提供)：胃轻瘫的特征是胃排空延迟，伴随着恶心、呕吐、饱腹感、早饱和疼痛，这对生活质量有毁灭性的影响。5年来，胃轻瘫临床研究联盟(GpCRC)提高了对这种疾病的了解，并提高了患者、医生和NIH对其护理的高级目标。关于它的病因、病程和治疗仍有许多需要了解，以此作为继续该联盟的理由。这个应用程序有三个具体目标。第一个目标是完成GpCRC的批准研究，包括NORIG，去甲替林与安慰剂治疗特发性胃瘫的试验(迄今招募的140名患者中的48人)，GLUMIT-DG，持续血糖监测和胰岛素泵治疗糖尿病胃轻瘫的安全性、可行性和潜在有效性的研究(迄今招募的40人中有2人在Univ进行了筛查。密歇根州的APRON，一项针对推定胃源性恶心的APRON与安慰剂的试验(2010年9月开始)，以及PBG，胃瘫的病理基础(计划进行200例活组织检查中的125例)。第二个目标是维护、扩展和完善胃轻瘫登记系统，该登记系统从2007年2月至2010年3月共登记了587名患者。我们将对所有患者进行4年的跟踪调查，有些患者将进行9年的跟踪调查。根据来自注册中心的见解，我们建议招募更多的患者来回答与胃瘫的发病机制、严重程度、并发症、治疗和结果有关的新问题。第三个目标将使用一种新的无线运动胶囊(WMC)来表征全身性运动障碍在推定胃瘫患者产生症状中的作用。本研究将定义胃、小肠和结肠的运输和收缩异常，并将不同的运动缺陷与胃轻瘫的不同症状特征联系起来，以提供与导致不同疾病表现的胃排空以外的因素有关的病因学见解。第三个目标的第二部分将包括一项针对胃排空和结肠运输延迟患者的渗透性泻药的安慰剂对照试验，以测试治疗远程运动障碍是否能改善胃瘫的一系列症状。对这一应用的研究将极大地促进对这种具有挑战性的疾病的发病机制、临床特征和治疗的知识基础。

DESCRIPTION (provided by applicant): Gastroparesis is characterized by delayed gastric emptying in association with nausea, vomiting, fullness, early satiety, and pain that has devastating impacts on quality of life. Over 5 years, the Gastroparesis Clinical Research Consortium (GpCRC) has improved understanding of this disorder and advanced goals of patients, physicians, and the NIH for its care. Much still needs to be learned about its etiology, course, and therapy that serve as rationales to continue the consortium. This application has 3 specific aims. The first aim is to complete approved studies of the GpCRC including NORIG, a trial of nortriptyline vs. placebo for idiopathic gastroparesis (48 of 140 patients recruited to date), GLUMIT-DG, a study of the safety, feasibility, and potential efficacy of continuous glucose monitoring and insulin pump therapy in diabetic gastroparesis (2 of 40 recruited to date with 2 screened at Univ. of Michigan, APRON, a trial of aprepitant vs. placebo for nausea of presumed gastric origin (initiating 9/2010), and PBG, the pathological basis of gastroparesis (125 biopsies of 200 planned). The second aim is to maintain, expand, and refine the Gastroparesis Registry that enrolled 587 patients from 2/2007-3/2010. We will follow all patients for 4 years and some for 9 years. Informed by insight from the Registry, we propose recruiting more patients to answer new questions relating to pathogenesis, severity, complications, therapies, and outcomes of gastroparesis. The third aim will employ a novel wireless motility capsule (WMC) to characterize the role of generalized dysmotility in producing symptoms in patients with presumed gastroparesis. This study will define abnormal gastric, small intestinal and colonic transit and contractility and relate different motor defects to distinct symptom profiles of gastroparesis to give pathogenic insight relating to factors other than gastric emptying that cause different disease manifestations. The second part of the third aim will include a placebo-controlled trial of an osmotic laxative in patients with delayed gastric emptying and colon transit to test if treating distant dysmotilities improve a range of symptoms of gastroparesis. The studies of this application will significantly advance the knowledge base of the pathogenesis, clinical features, and management of this challenging disorder.