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; 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.

抽象的： 胃轻瘫（GP）在延迟的情况下表现出具有慢性上胃肠道不动力症状 胃排空而没有任何机械障碍物。主观之间存在不一致之处 症状严重程度和GP的客观证据，可用的疗法受到限制 不良事件和不可预测的功效。因此，病理生理学，临床过程，结局和 治疗策略需要进一步调查。我们对NIDDK胃轻瘫的反应 RFA-DK-16-010下的财团（U01）具有以下目的： 1）完成由GPCRC发起的批准的研究，该研究需要招募GP患者 胃清洗注册表2及其临床数据和生物样本，并获得胃组织 在胃轻瘫（PBG）方案的病理基础下，某些患者接受手术时 用于失败的医疗疗法。该数据收集将有助于更多有关发病机理的知识， 病原体，症状严重程度分级，并发症，患者的治疗结果 GP和类似胃的表现，但胃排空正常。 2）作为一种新的诊断策略，我们建议确定内窥镜超声（EUS） - GP患者中的鼻肌的核心活检样品可以提供足够的组织 要进行完整的组织学分析，以专门解决Cajal的间质细胞的状态 神经元和平滑肌病理学。在重新确立了这一安全和成功之后 在一项接受内窥镜检查和手术活检的30名患者的研究中，所有患者 输入GPR3以及GPR2注册表将接受EUS的指导核心活检 穆斯科利斯（Muscularis Proprias）作为数据库的一部分。因此，我们将研究这种内窥镜检查是否 方法可以安全地替换手术以获得平滑肌组织，并将ICC发现与 症状，胃排空和治疗结果。 3）我们建议研究新的多巴胺D2/D3拮抗剂在 通过进行多中心，双重双重性，双中心，糖尿病或特发性病因 盲，随机，安慰剂对照，平行的三组研究，还将评估心脏 安全性和不利事件。该计划是为NIH与2种药物之一合作 开发新代理的公司，多巴胺D2/D3拮抗剂，没有心脏毒性。所有GPR3 将邀请患者参加2次平行的12周试验，以进行糖尿病和特发性病因 胃轻瘫。 如果我们被授予这项赠款，TTU研究团队将致力于促进执行 协议并根据GPCRC和NIDDK/NIH监督与其他中心合作。