A Phase 1b Trial of Oligomeric Procyanidin Complex in Combination with Metformin for Reduced AGE Levels in Prostate Cancer Patients Receiving Androgen Deprivation Therapy

中试研究项目1：低聚原花青素复合物与 美托洛尔用于降低接受雄激素去甲治疗的前列腺癌患者的AGE水平 治疗 研究综述 晚期糖基化终产物（AGEs）是糖代谢的副产物 和氧化应激。大量文献将AGEs与糖尿病和其他疾病的病理生理学联系起来， 慢性病U 54研究人员已经确定了AGEs在前列腺癌中的优先积累 (PCa)与正常血清和前列腺组织比较。此外，在PCa患者中， 年龄积累是较高的黑人与非洲血统（AAs）比欧洲裔美国人（EAs）。作为AGEs 似乎促进癌症存活和生长，限制其积累的干预措施可被视为 潜在的癌症治疗剂。这些药物可能是多方面治疗的有吸引力的组成部分 针对饮食不良、低收入、肥胖和缺乏锻炼的人群的治疗方案。这些是 所有已知会增加癌症负担的生活方式因素，通常在AA中普遍存在。研究 研究人员建议进行一项Ib期临床试验，研究两种潜在药物的组合，以减少AGE 水平-二甲双胍和低聚原花青素复合物（OPC）。每种药物都能降低AGE 在某些糖尿病（二甲双胍）或癌症（OPC）患者中的水平。他们的组合可能是 比单独使用任何一种药物都有效。这项研究将由来自南卡罗来纳州的Shanora Brown博士共同领导 州立大学（SCSU）和来自南卡罗来纳州霍林斯癌症医科大学的Michael Lilly博士 中心（MUSC-HCC）。作为Ib期研究，主要目的是确定药物的毒性 组合.然而，所有分析将比较AA和EA受试者的结果。目标1是进行阶段 二甲双胍和OPC联合治疗接受雄激素剥夺治疗（ADT）的PCa患者的Ib试验。 这一目标将由Lilly博士（MUSC-HCC）领导。目的2是进行相关的生化研究， 炎症和氧化应激。这一目标将由布朗博士（SCSU）领导。没有 迄今为止的研究已经调查了AGE对PCa治疗的影响。这项研究提供了一种新颖的、统一的 解释ADT对PCa反应较差、PCa发生率较高以及 肥胖、氧化应激和高血糖患者的生活质量。这种机械模型还可以 介导PCa结果中的癌症种族差异。

Pilot Research Project 1: A Phase 1b Trial of Oligomeric Procyanidin Complex in Combination with Metformin for Reduced AGE Levels in Prostate Cancer Patients Receiving Androgen Deprivation Therapy RESEARCH SUMMARY Advanced glycation endproducts (AGEs) are reactive metabolites produced as by-products of sugar metabolism and oxidative stress. An extensive literature links AGEs with the pathophysiology of diabetes mellitus and other chronic diseases. The U54 investigators have identified preferential accumulation of AGEs in prostate cancer (PCa) serum and tumor, compared with normal serum and prostate tissue. Furthermore, among PCa patients, AGE accumulation is higher in blacks with African ancestry (AAs) than in European Americans (EAs). As AGEs appear to promote cancer survival and growth, interventions to limit their accumulation may be viewed as potential cancer therapeutic agents. These agents may be attractive components of multi-faceted treatment regimens for populations with high prevalence of poor diet, low income, obesity, and lack of exercise. These are all lifestyle factors that are known to increase cancer burden, and are often prevalent in AAs. The study investigators propose to conduct a Phase Ib clinical trial of a combination of two potential agents to reduce AGE levels — metformin and oligomeric procyanidin complex (OPC). Each agent has been shown to reduce AGE levels in some patients with either diabetes mellitus (metformin) or cancer (OPC). Their combination may be more effective than either agent alone. The study will be co-led by Dr. Shanora Brown from South Carolina State University (SCSU) and Dr. Michael Lilly from the Medical University of South Carolina Hollings Cancer Center (MUSC-HCC). As a Phase Ib study, the primary objective will be to define toxicity for the drug combination. However, all analyses will compare results in AA and EA participants. Aim 1 is to conduct a Phase Ib trial of a combination of metformin and OPC in PCa patients receiving androgen deprivation therapy (ADT). This aim will be led by Dr. Lilly (MUSC-HCC). Aim 2 is to perform correlative biochemical studies of inflammation and oxidative stress during the Phase Ib trial. This aim will be led by Dr. Brown (SCSU). No studies to date have investigated AGE effects on PCa treatment. The proposed study provides a novel, unifying mechanism to account for the poorer PCa response to ADT, and the higher PCa incidence, as well as poorer quality of life, in patients with obesity, oxidative stress, and hyperglycemia. This mechanistic model may also mediate cancer racial disparities in PCa outcomes.