New Diagnosis and Treatment Approaches for Patients wit*

为患者提供新的诊断和治疗方法*

• 批准号: 8038863
• 负责人: RICHARD W MCCALLUM
• 金额: $ 4.56万
• 依托单位: TEXAS TECH UNIVERSITY HEALTH SCIS CENTER
• 依托单位国家: 美国
• 财政年份: 2010
• 资助国家: 美国
• 起止时间: 2010-04-01 至 2012-03-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/8038863
• 关键词: Diagnosis; Patients; Wit

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.

胃压迫是一种症状性慢性胃部疾病，其特征是胃排空延迟， 没有机械性阻塞这种情况被认为影响了多达500万人， 我们标准的药物治疗可能包括饮食调整，结合促动力和止吐 药物，放置胃造口术/空肠造口术管进行肠内营养和植入胃电 刺激器目前用促动力剂治疗胃轻瘫的药物治疗令人失望， 目前可用的选项有限。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，来源于 新的化学类别，氨基胍吲哚。据报道，替加色罗剂量为18和24 mg/天， 加速胃排空延迟患者的胃排空。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（FDA） 经管理部门批准的胃电刺激（GES）（美敦力公司， Minneapolis，MN），2000年3月根据人道主义器械豁免，用于缓解患者症状 患有糖尿病和特发性胃轻瘫虽然迄今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， 刺激参数是最佳的，长期有效性和安全性随访，糖尿病患者成功的预测因素 和特发性病因以及作用机制。该提案涉及三个目标： 目的1：使用剂量滴定法和双剂量滴定法确定替加色罗的疗效和耐受性。 盲态退出设计，主要终点反映上GI症状和质量的改善 胃轻瘫患者的生命周期（短期研究）。测量胃肌电活动，胃 还将进行排空、胃张力和调节内脏敏感性试验，以检验假设 替加色罗可以改善胃轻瘫的主观和客观方面。 目的2：研究高频电刺激的短期和长期疗效、安全性和作用机制。 胃轻瘫患者的GES（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。胃电图，恒压器，正电子发射 将整合断层扫描（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显著的改善 在GI症状中，需要识别和描述患者的生活质量但治疗失败。 目的3：建立一个大型数据库，提供人口统计学、症状和质量信息， 胃轻瘫患者的生活状态、病因、诊断测试数据、治疗和结果。