A Randomized, Blinded, Placebo-Controlled Clinical Trial to Evaluate Longeveron Mesenchymal Stem Cell (LMSC) Therapy for Treating The Metabolic Syndrome

一项评估 Longeveron 间充质干细胞 (LMSC) 疗法治疗代谢综合征的随机、盲法、安慰剂对照临床试验

• 批准号: 9348026
• 负责人: Joshua M Hare
• 金额: $ 15万
• 依托单位: LONGEVERON, LLC
• 依托单位国家: 美国
• 财政年份: 2017
• 资助国家: 美国
• 起止时间: 2017-09-30 至 2019-03-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/9348026
• 关键词: Address; Adult; Affect; Allogenic; Anti-Inflammatory Agents; Anti-inflammatory; B-Lymphocyte Subsets; Biological Assay; Blinded; Blood Chemical Analysis; Blood Pressure; Cardiac; Cardiovascular system; Cell Therapy; Cells; Cholesterol; Clinical; Clinical Trials; Clinical Trials Data Monitoring Committees; Coagulation Process; Controlled Clinical Trials; Dobutamine; Dose; Double-Blind Method; Enzyme-Linked Immunosorbent Assay; Epidemic; Fasting; Female; Fibrin fragment D; Fibrinogen; Flow Cytometry; Glucose; Glycosylated hemoglobin A; Health Surveys; Hematology; High Density Lipoproteins; Incidence; Individual; Inflammation; Inflammatory; Infusion procedures; Insulin; Interleukin-1; Interleukin-6; International; Intravenous; Lead; Lipids; Measurement; Measures; Mediating; Mesenchymal Stem Cells; Metabolic syndrome; Modeling; Monitor; Morbidity - disease rate; Non-Insulin-Dependent Diabetes Mellitus; Phase; Physical Performance; Placebo Control; Placebos; Positioning Attribute; Property; Quality of life; Questionnaires; Randomized; Reaction; Reading; Risk; Running; SF-36; Safety; Sampling; Serious Adverse Event; Serum; Stem cells; Stress; Study Subject; T-Lymphocyte; TNF gene; Technology; Testing; Therapeutic; Urinalysis; Urine; Vasodilation; Walking; blood glucose regulation; cardiovascular disorder risk; cytokine; effective therapy; endothelial dysfunction; fasting glucose; follow-up; immune activation; improved; indexing; inflammatory marker; insight; low density lipoprotein triglyceride; male; mortality; multipotent cell; patient population; phase 1 study; phase III trial; programs

The metabolic syndrome (MetS) is a cluster of factors that increases the risks for cardiovascular disease, type 2 diabetes mellitus, and mortality, and currently affects > 40% of US adults. MetS is associated with endothelial dysfunction, decreased circulating endothelial progenitor cells (EPCs), and a pro-inflammatory state. We have made the exciting discovery that therapy with allogeneic mesenchymal stem cells (MSCs) restores endothelial dysfunction and circulating EPCs towards normal the levels, and reduces markers of inflammation. Endothelial function represents a key driver of cardiovascular morbidity and mortality in MetS, and as such, restoring endothelial function could lead to clinical benefits in this patient population. We will conduct a clinical trial using Longeveron-produced allogeneic mesenchymal stem cells (LMSCs) delivered to subjects with MetS. In Phase I of this study, we will perform a dose-escalation Safety Run-In to first establish safety of LMSC therapy in subjects with MetS. After a safety review and approval from an independent data safety monitoring board (DMSB), Phase II of this Fast-Track Study will commence. This will entail a Randomized, Double-Blinded, Placebo-Controlled Phase on 40 subjects with MetS. The following specific aims will be examined. Specific Aim #1: To test the hypothesis that LMSCs are safe to intravenously-administer to subjects with MetS. We will examine for incidence of treatment-emergent serious adverse events (TE-SAEs); blood chemistry, hematology, coagulation, and urinalysis; and alloimmune reaction and T and B cell subsets to examine levels of immune activation. Specific Aim #2: To test the hypothesis that intravenously-administered LMSCs will improve endothelial dysfunction and increase circulating EPCs in subjects with MetS. We will examine endothelial dysfunction using flow-mediated vasodilation (FMD), and circulating EPCs by colony assays and flow cytometry. Specific Aim #3: To test the hypothesis that intravenously-administered LMSCs will improve systemic markers of inflammation in subjects with MetS. We will use ELISA to examine panels of inflammatory markers. Specific Aim #4: To test the hypothesis that intravenously-administered LMSCs will lead to clinical improvement in subjects with MetS. We will examine for changes in glucose control (hemoglobin A1c, fasting glucose, fasting insulin, HOMA), lipid profile (HDL, LDL, triglycerides, cholesterol), blood pressure and cardiac function, physical performance, and subject quality of life. We anticipate that the results of this study will lead to a much needed therapeutic for subjects with MetS. Longeveron is positioned to rapidly advance this program to a pivotal phase III trial if the results prove positive, and to bring this technology to market.

代谢综合征（MetS）是一组可增加2型心血管疾病风险的因素 糖尿病和死亡率，目前影响> 40%的美国成年人。MetS与内皮细胞 功能障碍、循环内皮祖细胞（EPC）减少和促炎状态。我们有 取得了令人兴奋的发现，同种异体间充质干细胞（MSC）治疗恢复内皮细胞， 功能障碍和循环EPCs向正常水平，并减少炎症标志物。内皮 功能是代谢综合征心血管发病率和死亡率的关键驱动因素，因此， 内皮功能可以在该患者群体中产生临床益处。我们将进行临床试验， Longeveron生产的同种异体间充质干细胞（LMSC）被输送给MetS受试者。同相 在本研究中，我们将进行剂量递增的安全性导入，以首先确定LMSC治疗的安全性， 患有MetS的受试者。经过独立数据安全监测委员会的安全审查和批准后 （DMSB），本快速通道研究的第II阶段将开始。这将需要一项随机、双盲、 安慰剂对照期，40例MetS受试者。将审查以下具体目标。 具体目的#1：检验LMSC静脉内给药于患有以下疾病的受试者是安全的假设： MetS。我们将检查治疗后出现的严重不良事件（TE-SAE）的发生率;血液 化学、血液学、凝血和尿分析;同种免疫反应以及T和B细胞亚群， 检查免疫激活水平。 具体目标#2：检验静脉内给予LMSC将改善内皮细胞增殖的假设。 功能障碍和增加循环EPCs与MetS的受试者。我们将检查内皮功能障碍 使用流动介导的血管舒张（FMD），和通过集落测定和流式细胞术的循环EPCs。 具体目标#3：检验静脉内给予LMSC将改善全身标志物的假设 代谢综合征患者的炎症反应我们将使用ELISA检测炎症标志物。 具体目标#4：检验静脉内给予LMSC将导致临床 MetS患者的改善。我们将检查血糖控制（血红蛋白A1 c， 空腹血糖、空腹胰岛素、HOMA）、血脂（HDL、LDL、甘油三酯、胆固醇）、血压 以及心脏功能、身体表现和受试者生活质量。 我们预计，本研究的结果将为MetS受试者提供急需的治疗方法。 如果结果证明是积极的，Longeveron将迅速推进该项目进入关键的III期试验， and to bring带来this technology技术to market市场.