New Diagnosis and Treatment Approaches for Patients wit*

胃轻瘫是一种以胃排空延迟为特征的慢性症状性胃病。 没有机械阻塞。这种情况被认为影响了多达500万人 我们。标准的医学治疗可能包括改变饮食，结合促动力和止吐。 药剂，放置胃造瘘管进行肠内营养，并植入胃电 刺激器。目前胃轻瘫的促动力药物药物治疗一直令人失望，因为 目前可用的选项有限。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 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 促进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。根据多中心研究产生的数据，美国食品和药物管理局 经批准的胃电刺激(GES)(ENTERRA治疗系统，美敦力， 明尼阿波利斯，明尼苏达州)在2000年3月根据人道主义设备豁免患者的症状缓解 患有糖尿病和特发性胃轻瘫。虽然到目前为止取得的一些成果令人鼓舞，但一些 重要的问题仍有待澄清，包括其在严格的双盲试验设计中的有效性， 刺激参数是糖尿病患者治疗成功的最佳、长期有效和安全的随访和预测因素 和特发性病因，以及作用机制。该提案涉及三个目标： 目的1：用剂量滴定法和双倍剂量滴定法测定替加色罗的疗效和耐受性 以Gl上段症状和质量改善为主要终点的盲法戒断设计 胃瘫患者的生活质量(短期研究)。胃肌电活动的测定 排空、胃张力和调节内脏敏感性也将被用来检验这一假设。 替加色罗可以改善胃轻瘫的主观和客观方面。 目的2：探讨高频电疗的近期和远期疗效、安全性及作用机制 胃轻瘫患者的胃电刺激(长期研究)。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、恒压、正电子发射 体层摄影(PET)成像、胃排空测试、GE反流测试和激素分析将整合在一起。 我们假设高频GES治疗将安全地实现并维持显著的改善 在G1症状中，需要识别和描述治疗失败的患者的生活质量。 目标3：建立一个大型数据库，以提供有关人口学、症状和质量的信息 胃轻瘫患者的生活状况、病因、诊断测试数据、治疗和结果。

Gastropresis 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 accomodation 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.