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/犹太医院在心血管医学方面拥有非常活跃的基础和临床研究项目，特别是在干细胞和心力衰竭 (HF)、左心室辅助装置 (LVAD) 和缺血性心肌病患者领域。来自心血管内科和胸心血管外科的研究人员组成的高度凝聚力的合作团队多年来在多项多中心试验中卓有成效地工作，表现出色。现有的临床基础设施，加上多年来针对细胞疗法开展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绝佳的平台。我们中心在心力衰竭患者中进行的首次 c-kit+ 心脏干细胞人体研究的成功证明了我们中心开展干细胞 I/II 期研究的能力（SCIPIO）。 CCTRN 研究将利用使 SCIPIO 成为可能的相同研究人员和基础设施。在此，我们提出 SENECA（针对终末期心脏衰竭的 StEm 细胞治​​疗），其中我们将测试冠状动脉内递送 CD34+ 细胞或非常小的胚胎样细胞 (VSEL) 的可行性、安全性（目标 1）和有效性（目标 2）植入 LVAD 后患有终末期缺血性心肌病 (ICM) 的患者。我们的假设是，细胞疗法将促进受损心肌的修复和再生，从而改善心脏功能、功能能力和整体生活质量，并将心肌功能恢复到允许考虑 LVAD 移植的程度。在目标 3 中，我们将确定与 CD34+ 细胞和 VSEL 在改善体内左室功能方面的有效性（或缺乏有效性）相关的患者特征和干细胞功能的体外参数。 SENECA 将是第一个针对人类 VSEL 的研究，也是第一个测试 CD34+ 细胞对终末期缺血性心力衰竭效果的对照试验。因此，该结果将是全新的，并可能为目前预后不佳的患者提供新的选择。因此，SENECA 的潜在影响是相当大的。此前尚未报道过针对 LVAD 和 ICM 患者的细胞疗法研究，尽管这些患者正是最需要细胞疗法的患者。因此，SENECA 将解决心脏病患者管理中的主要治疗空白。该试验有可能为终末期缺血性心脏病的治疗提供新的临床突破。