A multicenter, double-blind, randomized, placebo- controlled, parallel study to assess the efficacy of 5- HT4 agonist prucalopride for the treatment of diabetic and idiopathic gastroparesis

一项多中心、双盲、随机、安慰剂对照、平行研究，评估 5-HT4 激动剂普卡必利治疗糖尿病和特发性胃轻瘫的疗效

• 批准号: 10319436
• 负责人: Richard Warwick McCallum
• 金额: $ 40万
• 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 2027-07-31
• 项目状态: 未结题
• 来源: https://reporter.nih.gov/project-details/10319436
• 关键词: Abdominal Pain; Adverse event; Adverse reactions; Affect; Agonist; Antral; Biopsy; Buspirone; Chronic; Clinical; Clinical Research; Clinical Trials; Constipation; Control Groups; Diagnosis; Diagnostic; Diagnostic tests; Dissection; Double-Blind Method; Duodenum; Endoscopy; Enrollment; Etiology; Exhibits; FDA approved; Functional disorder; GPR4 gene; Gastric Emptying; Gastroparesis; Grant; Immunologics; Individual; Investigation; Knowledge; Large Intestine; Medical; Methodology; Methods; Mucous Membrane; National Institute of Diabetes and Digestive and Kidney Diseases; Nausea and Vomiting; Operative Surgical Procedures; Outcome; Pathogenesis; Pathologic; Patients; Peripheral Blood Mononuclear Cell; Pharmaceutical Preparations; Pharmacology; Placebo Control; Placebos; Play; Population; Protocols documentation; Pyloric sphincter structure; Radionuclide Imaging; Randomized; Reaction; Registries; Research; Research Design; Role; Safety; Sampling; Serotonin; Serotonin Receptors 5-HT4; Severities; Small Intestines; Smooth Muscle; Stomach; Subgroup; Symptoms; Testing; Time; Tissue Sample; Tissues; Treatment Efficacy; United States National Institutes of Health; Upper digestive tract structure; base; capsule; cell motility; clinical care; clinically relevant; cohort; design; diabetic; diabetic gastroparesis; diagnostic value; dysbiosis; gastric microbiota; gut microbiota; improved; insight; laxative; meetings; microbiota; randomized placebo controlled trial; receptor; reduce symptoms; response; symptomatic improvement; treatment duration; wireless

Abstract In the clinical world of diagnosis and treatment options for the spectrum of gastroparesis (GP) symptoms, there are still numerous and challenging needs to understand, while at the same time further investigating the pathophysiology of this entity, which affects > 10 million of patients in the US. GP patients exhibit a range of symptoms which do not always correlate with the objective tests we rely on for diagnosis, as well as for assessing their clinical reactions to pharmacological agents. Our response to the NIDDK Gastroparesis Consortium (U01) under RFA-DK-20-504 has the following aims: 1) A) Continue and complete already approved studies initiated by the GpCRC, which specifically entails enrolling qualified patients to Gastroparesis Registry 3, with all relevant clinical and bio-samples, including also PBMC isolation (peripheral blood mononuclear cells), as well as completing the Buspirone (BESST) clinical trial; B) Continue obtaining gastric antral and pyloric smooth muscle tissue samples at the time of surgeries to further advance our knowledge of pathological basis of gastroparesis (PBG) protocol. C) Investigate Pyloric Sphincter Abnormalities in Patients with Gastroparesis Symptoms (PSAGS) per the EndoFlip assessment protocol. B) Our additional proposals for the GP Registry 4 (GpR4) are: 1) During the routine EGD for GpR4 and possible PSAGS studies, we would like to collect samples of duodenal and gastric microbiota by obtaining brushings of gastric and duodenal mucosa; 2) biopsy antral muscularis propria tissue using Endoscopic Submucosal Dissection (ESD) methodology during upper GI endoscopy . 2) As a new research strategy, we propose to investigate whether microbiota obtained at the time of endoscopy by brushing the mucosa of the stomach and duodenum, will differ in their composition in idiopathic and diabetic GP and control patients. We hypothesize that dysbiosis of the upper GI microbiota may contribute to the delayed gastric emptying and symptoms in GP patients, particularly in the idiopathic subgroup of our cohort. 3) Our clinical trial proposal is to investigate the therapeutic efficacy of a new selective 5-HT4 receptor agonist, Pruclalopride, to improve the symptoms and gastric emptying in idiopathic and diabetic GP patients while at the same time having an excellent safety profile. A multicenter, double blind, randomized, placebo- controlled, parallel study, will be conducted were all GpR4 patients from all centers will be invited to be enroll into 2 parallel 4-week treatment periods with placebo or pruclalopride 2mg QD trial.

抽象的 在胃轻瘫（GP）症状的诊断和治疗选择的临床世界中，那里 仍然有很多且具有挑战性的需要理解，同时还要进一步研究 该实体的病理生理学影响了美国> 1000万患者。 GP患者表现出一系列 并不总是与我们依靠的客观测试相关的症状以及评估 他们对药理剂的临床反应。 我们对RFA-DK-20-504下的NIDDK胃轻瘫联盟（U01）的反应具有以下目的： 1）a）继续并完成由GPCRC发起的已经批准的研究，该研究特别需要 将合格的患者招募到胃清洗注册中心3，所有相关临床和生物样本，包括 还包括PBMC分离（外周血单核细胞），并完成胰蛋白酶（Besst） 临床试验； b）继续在当时获得胃肛门和幽门平滑肌组织样品 手术以进一步提高我们对胃轻瘫（PBG）方案的病理基础的了解。 c） 研究胃轻瘫症状（PSAG）患者的幽门括约肌异常 Endoflip评估方案。 b）我们关于GP注册表4（GPR4）的其他建议是：1）在GPR4的日常EGD期间 可能的PSAGS研究，我们希望通过获得十二指肠和胃菌群的样本 胃和十二指肠粘膜的刷牙； 2）使用内窥镜检查活检腹膜肌肉组织 上胃肠道内窥镜检查期间的粘膜粘膜下清除（ESD）方法。 2）作为一种新的研究策略，我们建议研究是否在内窥镜检查时获得微生物群 通过刷胃和十二指肠的粘膜，它们在特发性和 糖尿病GP和对照患者。我们假设上胃肠道菌群的营养不良可能有助于 GP患者的胃排空和症状延迟，尤其是在我们的特发性亚组中 队列。 3）我们的临床试验建议是研究新的选择性5-HT4受体激动剂的治疗功效， pruclalopride，以改善特发性和糖尿病GP患者的症状和胃排空 同时拥有出色的安全性。多中心，双盲，随机，安慰剂 - 将邀请所有中心的所有GPR4患者进行受控，并行研究 通过安慰剂或pruclalopride 2mg QD试验，将2平行于4周平行的治疗期。