Continuation of the NIDDK Gastroparesis Consortium

胃轻瘫（GP）是一种胃动力功能紊乱，以胃排空延迟为特征，常伴有慢性恶心和呕吐、早期饱腹感、餐后饱腹感、腹痛和可能需要营养支持的营养不良。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）做出了一系列重要的贡献，以提高我们对这种疾病的理解，这些观察结果有助于我们的患者和他们的医生，并达到改善胃轻瘫管理的目标。因此，我们提出该申请的以下具体目标：# 1：完成GpCRC发起的正在进行和已批准的研究；# 2：维护、扩展和完善GP登记处，并通过进一步深入分析GpR临床数据和生物样本，解决与GP患者的发病机制、并发症和临床结果相关的重要问题；# 3：开展新的多中心研究胃轻瘫的病因、发病机制、诊断和治疗方案。TTUHSC建议进行一项为期4个月的双盲安慰剂对照试验（一期），并进行为期8个月的“最佳临床护理”随访（二期），以评估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标是：1)记录多潘立酮对GP患者的疗效；2)比较多潘立酮对糖尿病患者和特发性病因的疗效；3)研究最优剂量；4)探讨预测最佳临床反应的人口学和临床因素；5)评估安全。与FDA批准的促动力学药物甲氧氯普胺（也是一种多巴胺拮抗剂，具有止吐和促动力学特性）不同，多潘立酮具有长期给药的良好安全性。由于多潘立酮在美国的可及性非常有限（通过FDA协议），许多有关其疗效、治疗剂量和副作用的问题仍未得到解答。因此，我们提出了这项研究来解决这些问题。

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.