University of Louisville Regional Clinical Center for the CCTRN

路易斯维尔大学 CCTRN 区域临床中心

• 批准号: 8448108
• 负责人: Roberto Bolli
• 金额: $ 44.55万
• 依托单位: UNIVERSITY OF LOUISVILLE
• 依托单位国家: 美国
• 财政年份: 2012
• 资助国家: 美国
• 起止时间: 2012-03-22 至 2019-02-28
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/8448108
• 关键词: Activities of Daily Living; Address; Affect; Area; Basic Science; CD34 gene; Cardiac; Cardiac Surgery procedures; Cardiomyopathies; Cardiovascular Surgical Procedures; Cardiovascular system; Cell Therapy; Cell physiology; Cells; Cellular biology; Characteristics; Clinical; Clinical Research; Collaborations; Commit; Coupled; Effectiveness; Embryo; Enrollment; Environment; Event; Faculty; Goals; Heart failure; Hospitals; Human; Human Resources; Implant; In Vitro; Infarction; Institution; Left; Letters; Life; Medicine; Motivation; Multicenter Trials; Myocardial; Myocardial Ischemia; Myocardium; Names; Natural regeneration; Patients; Performance; Personnel Staffing; Phase; Population; Positioning Attribute; Postdoctoral Fellow; Proto-Oncogene Protein c-kit; Quality of life; Recovery; Reporting; Research; Research Infrastructure; Research Personnel; Resources; Safety; Staging; Stem cells; Testing; Therapeutic; Thoracic Surgical Procedures; Time; Universities; Work; base; clinical infrastructure; control trial; follower of religion Jewish; human study; implantation; improved; in vivo; injured; insight; member; novel; outcome forecast; phase 1 study; phase 2 study; phase 3 study; pre-clinical research; preclinical study; programs; repaired; stem cell population; stem cell therapy; success; ventricular assist device

DESCRIPTION (provided by applicant): The University of Louisville/Jewish Hospital has a remarkably vibrant basic and clinical research program in cardiovascular medicine, particularly in the area of stem cells and patients with heart failure (HF), left ventricular assist devices (LVADs), and ischemic cardiomyopathy. A highly cohesive and collegial team of investigators from the Divisions of Cardiovascular Medicine and Thoracic and Cardiovascular Surgery has worked productively for many years in several multicenter trials, with outstanding performance. This existing clinical infrastructure, coupled with the strong preclinical research work conducted on cell-based therapies for several years, provides a superb platform for participation in the CCTRN as a Regional Clinical Center. The ability of our Center to carry out Phase l/ll studies of stem cells is exemplified by our success i performing the first in-human study of c-kit+ cardiac stem cells in patients with HF (SCIPIO). The same investigators and the infrastructure that made SCIPIO possible will be leveraged for the CCTRN studies. Here we propose SENECA (StEm cell treatmeNt for End stage CArdiac failure), in which we will test the feasibility and safety (Aim 1) and efficacy (Aim 2) of intracoronary delivery of CD34+ cells or very small embryonic-like cells (VSELs) to patients with end-stage ischemic cardiomyopathy (ICM) following implantation of an LVAD. Our hypothesis is that cell therapy will promote repair and regeneration of the injured myocardium, resulting in improved cardiac function, functional capacity, and overall quality of life, and recovery of myocardial function to a degree that permits consideration of LVAD explantation. In Aim 3, we will identify patient characteristics and in vitro parameters of stem cell function that are associated with effectiveness (or lack thereof) of CD34+ cells and VSELs in improving LV function in vivo. SENECA will be the first study of VSELs in humans and the first controlled trial to test the effects of CD34+ cells in end-stage ischemic HF. Therefore, the results will be entirely novel and may provide a new option for patients who currently have a dismal prognosis. Thus, the potential impact of SENECA is considerable. No cell therapy study has ever been reported before in patients with LVADs and ICM, although these are the very patients who need it the most. Therefore, SENECA will address a major therapeutic gap in the management of cardiac patients. This trial has the potential to provide a novel clinical breakthrough in the treatment of end-stage ischemic heart disease.

描述（由申请人提供）： 路易斯维尔大学/犹太人医院在心血管医学方面具有非常活跃的基础和临床研究计划，特别是在干细胞和心力衰竭（HF），左心室辅助装置（LVADS）和缺血性心肌病的地区。来自心血管医学和胸腔和心血管手术部门的调查人员组成的高度凝聚力和大学团队在多个多中心试验中有效地工作了多年，表现出色。这项现有的临床基础设施以及几年对基于细胞的疗法进行的强大临床前研究工作为参与CCTRN作为区域临床中心提供了一项出色的平台。我们的成功I对我们的成功I进行了对HF（SCIPIO）患者的C-KIT+心脏干细胞进行的首次人类研究，从而体现了我们中心进行干细胞的L/LL研究期研究的能力。相同的研究人员和使Scipio成为可能的基础设施将被利用用于CCTRN研究。在这里，我们提出了Seneca（用于终阶段心脏衰竭的干细胞处理），其中我们将测试可行性和安全性（AIM 1）和疗效（AIM 2）CD34+细胞的冠状动脉内递送或对末期缺血性心肌疗法（ICM）的患者的胚胎样细胞（VSEL）（VSEL）。我们的假设是细胞疗法将促进受伤的心肌的修复和再生，从而改善心脏功能，功能能力和整体生活质量以及心肌功能的恢复，以便允许考虑LVAD膨胀的程度。在AIM 3中，我们将确定与CD34+细胞的有效性（或缺乏）相关的干细胞功能的患者特征和体外参数，并在改善体内LV功能方面。塞内卡（Seneca）将是对人类VSEL的首次研究，也是第一个测试CD34+细胞在末期缺血性HF中的影响的对照试验。因此，结果将是完全新颖的，可能会为目前有沮丧预后的患者提供新的选择。因此，塞内卡的潜在影响很大。 LVADS和ICM患者以前从未有过细胞疗法研究，尽管这些患者最需要它。因此，Seneca将解决心脏病患者治疗的主要治疗差距。该试验有可能在治疗终阶段缺血性心脏病方面提供新的临床突破。