Continuation of the NIDDK Gastroparesis Consortium

NIDDK 胃轻瘫联盟的延续

• 批准号: 8114332
• 负责人: Richard Warwick McCallum
• 金额: $ 41.51万
• 依托单位: TEXAS TECH UNIVERSITY HEALTH SCIS CENTER
• 依托单位国家: 美国
• 财政年份: 2008
• 资助国家: 美国
• 起止时间: 2008-09-30 至 2016-08-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/8114332
• 关键词: Abdominal Pain; Address; Adverse effects; Affect; Antiemetics; Asses; Chronic; Clinical; Clinical Data; Clinical Research; Diagnosis; Disease; Domperidone; Dopamine Antagonists; Dose; Double-Blind Method; Etiology; FDA approved; Failure; Gastric Emptying; Gastroparesis; Goals; Knowledge; Lead; Malnutrition; Methods; Metoclopramide; Multicenter Studies; National Institute of Diabetes and Digestive and Kidney Diseases; Nausea and Vomiting; Nutritional Support; Outcome; Pathogenesis; Patients; Phase; Physicians; Property; Protocols documentation; Public Health; Quality of life; Registries; Research; Risk; Safety; Satiation; Series; Stomach; Therapy Clinical Trials; Time; Treatment Efficacy; Woman; clinical care; diabetic; follow-up; improved; meetings; novel therapeutics; placebo controlled study; randomized trial; response

DESCRIPTION (provided by applicant): Gastroparesis (GP) is a disorder of gastric motilityfunction characterized by a delay in gastric emptying, frequently associated with chronic nausea and vomiting, early satiety, postprandial fullness, abdominal pain, and malnutrition that may require nutritional support. GP has a devastating impact on quality of life and predominantly affects younger women. In the past 5 years, the Gastroparesis Clinical Research Consortium (GpCRC) has made a series of important contributions to improve our understanding of this disorder and these observations have advenced the goals of helping our patients and their physicians as well as meeting the goals to improve the management of gastroparesis. We therefore propose the following specific aims for this application: # 1: To complete the ongoing and approved studies initiated by the GpCRC; # 2: To maintain, expand, and refine the GP Registry, and to address important questions related to the pathogenesis, complications and clinical outcome in GP patients by further in-depth analysis of GpR clinical data and biosamples; # 3: To conduct new multicenter studies of gastroparesis investigating the etiology, pathogenesis, diagnosis, and treatment options. TTUHSC is proposing a double-blind, "time- to- failure" placebo controlled trial (phase 1) of 4 months duration with "a best clinical care" follow up (phase 2) of 8 months duration study to evaluate the efficacy and safety of domperidone in gastroparesis. The principal objectives of this multicenter, randomized trial are to:1) Document the efficacy of domperidone in GP patients; 2) Compare domperidone's efficacy in diabetics vs. idiopathic etiologies;3) Investigate the optimal dose or doses; 4) Explore the demographic and clinical factors which predict the best clinical response; 5) Asses safety. Unlike the FDA approved prokinetic agent, metoclopramide, which is also a dopamine antagonist, with antiemetic and prokinetic properties, domperidone has an exellent safety profile for long- term administration. Due to the very restricted accessibility of domperidone in US (through the FDA protocol) many questions related to its efficacy, therapeutic dosing and side effects still remain unanswered. Therefore, we have proposed this study to resolve these questions. PUBLIC HEALTH RELEVANCE: This research underscores the public health significance of gastroparesis (GP) including; the need to develop effective methods for management of GP, the need to identify patients who are at risk of progression to more severe GP, to identify the key cellular changes that lead to GP, and to initiate several novel, therapeutic trials that have the potential to directly influence the quality of life of patients with GP and also in turn provide new knowledge for physicians to treat these patients.

描述（申请人提供）：胃轻瘫（GP）是一种胃动力功能障碍，其特征是胃排空延迟，常伴有慢性恶心和呕吐、早饱、餐后饱胀、腹痛和营养不良，可能需要营养支持。全科医生对生活质量有毁灭性的影响，主要影响年轻女性。在过去的5年里，胃轻瘫临床研究联盟（GpCRC）做出了一系列重要贡献，以提高我们对这种疾病的理解，这些观察结果已经达到了帮助我们的患者及其医生的目标，并达到了改善胃轻瘫管理的目标。因此，我们提出了本申请的以下具体目标：#1：完成GpCRC发起的正在进行的和已批准的研究;#2：维护、扩展和完善GP登记研究，并通过进一步深入分析GpR临床数据和生物样本来解决GP患者中与发病机制、并发症和临床结局相关的重要问题;#3：开展新的胃轻瘫多中心研究，调查病因、发病机制、诊断和治疗方案。TTUHSC提出了一项为期4个月的双盲、“至失败时间”安慰剂对照试验（1期）和为期8个月的“最佳临床护理”随访（2期）研究，以评价多潘立酮治疗胃轻瘫的疗效和安全性。这项多中心随机试验的主要目的是：1）记录多潘立酮在GP患者中的疗效; 2）比较多潘立酮在糖尿病患者与特发性病因中的疗效;3）研究最佳剂量; 4）探索预测最佳临床反应的人口统计学和临床因素; 5）评估安全性。与FDA批准的促动力剂甲氧氯普胺不同，甲氧氯普胺也是一种多巴胺拮抗剂，具有止吐和促动力特性，多潘立酮对于长期给药具有极好的安全性。由于多潘立酮在美国的可及性非常有限（通过FDA方案），许多与其疗效、治疗剂量和副作用相关的问题仍然没有答案。因此，我们提出了这项研究来解决这些问题。 公共卫生相关性：这项研究强调了胃轻瘫（GP）的公共卫生意义，包括;需要开发用于GP管理的有效方法，需要鉴定处于进展为更严重GP的风险中的患者，鉴定导致GP的关键细胞变化，并启动几种新的，治疗试验有可能直接影响GP患者的生活质量，并反过来为医生治疗这些患者提供新的知识。