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

代谢综合征(METS)是一组增加2型心血管疾病风险的因素 糖尿病和死亡率，目前影响着40%的美国成年人。蛋氨酸与血管内皮细胞相关 功能障碍，循环内皮祖细胞(EPC)减少，以及促炎状态。我们有 令人兴奋的发现，用异基因间充质干细胞(MSCs)治疗可以恢复内皮细胞 功能障碍和循环内皮祖细胞接近正常水平，并减少炎症标志物.内皮细胞 功能是MET心血管发病率和死亡率的关键驱动因素，因此，恢复 内皮功能可以在这一患者群体中带来临床益处。我们将进行临床试验，使用 Longeveron生产的同种异体间充质干细胞(LMSCs)被移植到患有甲硫氨酸的受试者。同相 在这项研究中，我们将进行剂量递增安全磨合，以首先确定LMSC治疗的安全性 大都会军团的受试者。经过独立数据安全监测委员会的安全审查和批准 (DMSB)，这项快速通道研究的第二阶段将开始。这将需要一个随机的，双盲的， 40名服用METS的受试者的安慰剂控制期。将审查以下具体目标。 具体目标1：验证LMSCs可以安全静脉注射的假设-对患有 大都会队。我们将检查治疗紧急严重不良事件(TE-SAE)的发生率；血液 化学、血液学、凝血和尿液分析；以及同种免疫反应和T和B细胞亚群 检查免疫激活水平。 具体目标2：检验静脉注射LMSCs将改善内皮细胞的假设 甲状旁腺素受试者功能障碍和循环内皮祖细胞增加。我们将检查内皮功能障碍 采用流式血管扩张技术(FMD)，并通过集落试验和流式细胞术检测循环内皮祖细胞。 具体目标3：检验静脉注射LMSCs将改善系统标志物的假设 METS受试者的炎症反应。我们将使用ELISA法检查炎症标志物的面板。 具体目标4：检验静脉注射LMSCs将导致临床 大都会歌舞团的科目有所改善。我们将检查血糖控制的变化(血红蛋白A1c， 空腹血糖、空腹胰岛素、HOMA)、血脂(高密度脂蛋白、低密度脂蛋白、甘油三酯、胆固醇)、血压 心功能、体能表现和受试者的生活质量。 我们预计，这项研究的结果将导致对甲硫氨酸转氨酶患者急需的治疗。 如果结果证明是阳性的，Longeveron公司将迅速将该计划推进到关键的III阶段试验， 并将这项技术推向市场。

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.