New Diagnosis and Treatment Approaches for Patients wit*

描述(由申请人提供)： 胃紧张症是一种有症状的慢性胃病，其特征是胃排空延迟，无机械性梗阻。据认为，在美国有多达500万人患有这种疾病。标准的医疗治疗可能包括改变饮食，联合使用促动力和止吐药物，放置胃造瘘管/肠造口管进行肠内营养，以及植入胃电刺激器。由于目前可供选择的药物有限，目前胃轻瘫的促动力药物药物治疗一直令人失望。胃轻瘫的诊断和治疗需要新的观念。 替加色罗(Zelnorm)是一种选择性5-HT4受体激动剂，具有促动力作用，来源于一种新的化学类别-氨基胍吲哚。据报道，每天18毫克和24毫克的替加色罗可加速胃排空延迟患者的胃排空。目前还没有临床试验报告症状反应。基于多中心研究的数据，美国食品和药物管理局于2000年3月批准了胃电刺激(GES)(明尼苏达州美敦力ENTERRA Treatment System，明尼阿波利斯，明尼阿波利斯)，豁免人道主义设备，用于糖尿病和特发性胃瘫患者的症状缓解。虽然到目前为止获得的一些结果是令人鼓舞的，但仍有一些重要的问题需要澄清，包括它在严格的双盲试验设计中的有效性，哪些刺激参数是最佳的，长期有效性和安全性随访，糖尿病和特发性病因成功的预测因素，以及作用机制。该提案涉及三个目标： 目的：采用剂量滴定和双盲停药设计，以主要终点反映胃瘫患者Gl以上症状和生活质量的改善为主要终点，评价替加色罗的疗效和耐受性(短期研究)。还将进行胃肌电活动、胃排空、胃张力和调节[原文如此]内脏敏感性的测量，以验证替加色罗可以改善胃瘫的主观和客观方面的假设。 目的：探讨高频胃电刺激治疗胃轻瘫患者的近期和远期疗效、安全性及作用机制。我们将首先进行双盲交叉设计试验，然后进行长期跟踪，以实现这些目标。胃电、稳压、正电子发射断层扫描(PET)成像、胃排空试验、GE反流试验和激素检测将整合在一起。我们假设高频GES治疗将安全地实现并维持患者的G1症状和生活质量的显著改善，但治疗失败需要确定和描述。 目的3：建立一个大型数据库，以提供胃轻瘫患者的人口统计学、症状和生活质量状况、病因、诊断测试数据、治疗和结果的信息

DESCRIPTION (provided by applicant): Gastropresis [sic] is a symptomatic chronic disorder of the stomach characterized by delayed gastric emptying in the absence of mechanical obstruction. This condition is thought to affect up to 5 million individuals in the US. Standard medical therapy may involve dietary modifications, combining prokinetic and antiemetic agents, placing gastrostomy/jenunostomy tubes for enteral nutrition and implanting a gastric electrical stimulator. Current medical therapy of gastroparesis with prokinetic agents has been disappointing due to the limited options currently available. New concepts for diagnosis and treatment of gastroparesis are needed. Tegaserod (Zelnorm) is a selective partial 5-HT4 receptor agonist with prokinetic effects, derived from a new chemical class, the aminoguanidine indoles. Tegaserod in doses of 18 and 24 mg/day was reported to accelerate gastric emptying in patients with delayed gastric emptying. There are no clinical trials reporting symptom responses. Based on the data generated in multicenter studies, the United States Food and Drug Administration approved gastric electrical stimulation (GES) (ENTERRA Therapy System, Medtronic, Minneapolis, MN) in March 2000 under a Humanitarian Device Exemption for symptomatic relief in patients with diabetic and idiopathic gastroparesis. While some results obtained so far are encouraging, a number of important issues remain to be clarified including its efficacy in rigorous double-blind trial design, which stimulation parameters are optimal, long-term efficacy and safety follow-up, predictors of success in diabetic and idiopathic etiologies, and mechanisms of action. This proposal addresses three goals: Aim 1: To determine the efficacy and tolerability of tegaserod using a dose-titration approach and double blind withdrawal design with the primary endpoint reflecting improvement in upper Gl symptoms and quality of life in gastroparetic patients (short-term study). Measurements of gastric myoelectrical activity, gastric emptying, gastric tone and accommodation [sic] visceral sensitivity will also be performed to test the hypothesis that tegaserod can improve both subjective and objective aspects of gastroparesis. Aim 2: To investigate short and long-term efficacy, safety and mechanisms of action of high-frequency GES in gastroparetic patients (long-term study). We will initially conduct a double-blind crossover design trial and then long-term follow-up to achieve these goals. Electrogastrogram, barostat, positron emission tomography (PET) imaging, gastric emptying test, GE reflux testing and hormonal assays will be integrated. We hypothesize that high-frequency GES therapy will safely achieve and sustain a significant improvement in Gl symptoms, quality of life of patients but treatment failures need to be identified and profiled. Aim 3: To establish a large database to provide information on demographics, symptoms and quality of life status, etiologies, diagnostic testing data, therapies and outcomes of gastroparetic patients