New Diagnosis and Treatment Approaches for Patients wit*

描述（由申请人提供）： 胃压迫[原文如此]是一种有症状的慢性胃部疾病，其特征是在没有机械性梗阻的情况下胃排空延迟。这种情况被认为影响了美国多达500万人。标准的药物治疗可能包括饮食调整，结合促动力和止吐剂，放置胃造口术/空肠造口术管进行肠内营养和植入胃电刺激器。目前的药物治疗胃轻瘫与促动力剂已令人失望，由于有限的选择，目前可用。胃轻瘫的诊断和治疗需要新的概念。 替加色罗（Zelnorm）是一种具有促动力作用的选择性部分5-HT 4受体激动剂，衍生自一种新的化学类别，氨基胍吲哚。据报告，替加色罗18和24 mg/天剂量可加速胃排空延迟患者的胃排空。没有临床试验报告症状缓解。根据多中心研究中生成的数据，美国食品药品监督管理局于2000年3月根据人道主义器械豁免批准胃电刺激（GES）（Medtronic，Minneapolis，MN）用于缓解糖尿病和特发性胃轻瘫患者的症状。虽然到目前为止获得的一些结果是令人鼓舞的，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的疗效，刺激参数是最佳的，长期疗效和安全性随访，成功的糖尿病和特发性病因的预测因素，以及作用机制。该提案涉及三个目标： 目标1：使用剂量滴定方法和双盲停药设计确定替加色罗的疗效和耐受性，主要终点反映胃轻瘫患者的上GI症状和生活质量的改善（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，以检验替加色罗可以改善胃轻瘫的主观和客观方面的假设。 目的2：研究高频胃电刺激治疗胃轻瘫患者的短期和长期疗效、安全性和作用机制（长期研究）。我们最初将进行双盲交叉设计试验，然后进行长期随访以实现这些目标。将整合胃电图、恒压器、正电子发射断层扫描（PET）成像、胃排空试验、GE反流试验和激素测定。我们假设高频GES治疗将安全地实现并维持GI症状、患者生活质量的显著改善，但需要识别和分析治疗失败。 目标3：建立大型数据库，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、治疗和结局等信息

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