New Concepts for Advancing Knowledge in Basic Science, Clinical, and Therapeutic Aspects of Gastroparesis

增进胃轻瘫基础科学、临床和治疗方面知识的新概念

• 批准号: 10021025
• 负责人: Richard Warwick McCallum
• 金额: $ 38.24万
• 依托单位: TEXAS TECH UNIVERSITY HEALTH SCIENCES CENTER AT EL PASO
• 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 2022-08-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/10021025
• 关键词: Abdominal Pain; Acupuncture Therapy; Address; Adverse event; Affect; Antiemetics; Antral; Applications Grants; Award; Basic Science; Biopsy; Biopsy Specimen; Cardiac; Cardiotoxicity; Cardiovascular system; Chronic; Clinical; Clinical Data; Clinical Research; Clinical Treatment; Clinical Trials; Core Biopsy; Data; Data Collection; Databases; Demographic Analyses; Devices; Diagnosis; Diagnostic; Diagnostic tests; Disease; Dopamine; Double-Blind Method; Endoscopic Ultrasonography; Enrollment; Epigastric; Etiology; Evaluation; Functional disorder; GPR3 gene; Gastric Emptying; Gastric Pacemakers; Gastric Tissue; Gastroparesis; Goals; Grant; Guidelines; Health Sciences; Histologic; Impairment; Implant; Individual; Interstitial Cell of Cajal; Investigation; Knowledge; Mechanics; Medical; Methodology; Methods; Modality; Morphology; Multicenter Studies; Muscle; Myenteric Plexus; National Institute of Diabetes and Digestive and Kidney Diseases; Nausea and Vomiting; Neurons; New Agents; Observational Study; Obstruction; Operative Surgical Procedures; Outcome; Pain; Pathogenesis; Pathologic; Pathology; Patients; Pharmacologic Substance; Placebos; Population; Protocols documentation; Publishing; Quality of life; Randomized; Registries; Research; Risk; Safety; Sampling; Severities; Smooth Muscle; Stomach; Structure; Supervision; Symptoms; Syndrome; Testing; Texas; Therapeutic; Thick; Tissue Sample; Tissues; Treatment Efficacy; Treatment outcome; United States National Institutes of Health; Universities; Upper digestive tract structure; Wireless Technology; Work; capsule; cell motility; design; diabetic; diabetic patient; disabling symptom; early satiety; experience; meetings; motility disorder; novel diagnostics; novel therapeutics; procedure safety; reduce symptoms; research study; response; success; treatment response; treatment strategy; week trial

Abstract: Gastroparesis (GP) presents with chronic upper GI dysmotility symptoms in the setting of delayed gastric emptying without any mechanical obstruction. Inconsistencies exist between subjective symptom severity and objective evidence of GP, and available therapies are limited by accompanying adverse events and unpredictable efficacy. Hence the pathophysiology, clinical course, outcomes and treatment strategies require further investigation. Our response to the NIDDK Gastroparesis Consortium (U01) under RFA-DK-16-010 has the following aims: 1) To complete approved studies initiated by the GpCRC which entails enrolling GP patients to Gastroparesis Registry 2 with their clinical data and bio-samples as well as obtain gastric tissue under the pathological basis of gastroparesis (PBG) protocol, when some patients undergo surgery for failed medical therapy. This data collection will contribute more knowledge about pathogenesis, pathomorphology, symptoms severity grading, complications, treatment outcomes in patients with GP and gastroparesis-like presentation but normal gastric emptying. 2) As a new diagnostic strategy, we propose to determine whether endoscopic ultrasound (EUS)- guided core biopsy samples of antral muscularis propria in GP patients can provide sufficient tissue for full histologic analysis to specifically address status of interstitial cell of Cajal, myenteric plexus neurons and smooth muscle pathology. After reconfirming the safety and success of this methodology in a study of 30 patients receiving both endoscopic and surgical biopsies all patients entering GpR3 as well as GpR2 registry will undergo EUS guided core biopsies of the antral muscularis propria as part of the database. Therefore we will investigate whether this endoscopic method can safely replace surgery to obtain smooth muscle tissue and correlate ICC findings with symptoms, gastric emptying and treatment outcome. 3) We propose to investigate the therapeutic efficacy of a new Dopamine D2/D3 antagonist in gastroparetic patients of either diabetic or idiopathic etiology by performing a multicenter, double- blind, randomized, placebo-controlled, parallel three-group study which will also assess cardiac safety and adverse event. The plan is for the NIH to partner with one of the 2 pharmaceutical companies developing new agents, Dopamine D2/D3 antagonists with no cardiac toxicity. All GpR3 patients will be invited to enroll into 2 parallel 12 week trials for diabetic and idiopathic etiologies of gastroparesis. If we are awarded this grant, TTU research team is committed to facilitate the execution of the protocols and collaborate with other Centers under GpCRC and NIDDK/NIH supervision.

摘要： 胃轻瘫（GP）表现为慢性上消化道动力障碍症状， 胃排空无任何机械性梗阻。主观与主观之间存在着不可分割性 GP的症状严重程度和客观证据以及可用的治疗受到伴随的限制。 不良事件和不可预测的疗效。因此，病理生理学，临床过程，结果和 治疗策略需要进一步研究。我们对NIDDK胃轻瘫的反应 根据RFA-DK-16-010，联合体（U 01）具有以下目标： 1)完成GpCRC发起的获批研究，需要招募GP患者， 胃轻瘫登记研究2及其临床数据和生物样本，并获得胃组织 根据胃轻瘫（PBG）方案的病理基础，当一些患者接受手术时， 因为药物治疗失败该数据收集将有助于更多关于发病机制的知识， 病理形态学，症状严重程度分级，并发症，患者的治疗结果 GP和胃瘫样表现，但胃排空正常。 2)作为一种新的诊断策略，我们建议确定内镜超声（EUS）- GP患者的胃窦固有肌层引导空芯活检样本可以提供足够的组织 进行全面的组织学分析，以明确Cajal间质细胞、肌间神经丛 神经元和平滑肌病理学。在再次确认安全性和成功后， 方法学在30例接受内窥镜和手术活检的患者中进行研究，所有患者 进入GpR 3和GpR 2登记研究的患者将接受EUS引导的胃窦核心活检 作为数据库的一部分。因此，我们将研究这种内窥镜 方法可以安全地代替手术获得平滑肌组织，并将ICC结果与 症状、胃排空和治疗结果。 3)我们建议研究一种新的多巴胺D2/D3拮抗剂在 通过对糖尿病或特发性胃轻瘫患者进行多中心、双 一项设盲、随机、安慰剂对照、平行三组研究，也将评估心脏 安全性和不良事件。该计划是为美国国立卫生研究院合作的两个制药 公司开发新的药物，多巴胺D2/D3拮抗剂，没有心脏毒性。所有GpR 3 将邀请患者入组2个平行的12周试验，用于糖尿病和特发性病因， 胃轻瘫 如果我们获得这笔赠款，TTU研究团队致力于促进执行 在GpCRC和NIDDK/NIH监督下与其他中心合作。