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

先导研究项目1：低聚原花青素复合体1b期试验 二甲双胍用于前列腺癌去雄激素患者的降龄治疗 治疗法 研究综述 晚期糖基化终末产物(Ags)是糖代谢的副产物，是一种反应性代谢产物。 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。U54研究人员发现前列腺癌患者AGEs优先积聚 (Pca)血清和肿瘤，与正常血清和前列腺组织比较。此外，在PCa患者中， 具有非洲血统的黑人(AAs)的年龄积累高于欧洲裔美国人(EAs)。随着年龄的增长 似乎可以促进癌症的存活和生长，但限制其积累的干预措施可能被视为 潜在的癌症治疗药物。这些药物可能是多方面治疗的诱人成分。 针对饮食不佳、低收入、肥胖和缺乏锻炼的高患病率人群的养生法。这些是 所有已知会增加癌症负担的生活方式因素，通常在AAS中普遍存在。这项研究 研究人员建议进行两种潜在药物组合的Ib期临床试验，以降低年龄 水平-二甲双胍和低聚原花青素复合体(OPC)。研究表明，每种药物都能降低年龄。 糖尿病(二甲双胍)或癌症(OPC)患者的血药浓度。它们的组合可能是 比单独使用任何一种药物都更有效。这项研究将由南卡罗来纳州的沙诺拉·布朗博士共同领导 南卡罗来纳州霍林斯癌症医科大学的迈克尔·礼来博士 中心(MUSC-HCC)。作为一项第一阶段研究，主要目标将是确定该药物的毒性 组合。然而，所有分析都将比较AA和EA参与者的结果。目标1是进行一个阶段 在接受雄激素剥夺治疗(ADT)的PCa患者中联合应用二甲双胍和OPC的IB试验。 这一目标将由礼来博士(MUSC-HCC)领导。目标2是进行相关的生化研究 Ib期试验期间的炎症和氧化应激。这一目标将由布朗博士(SCSU)领导。不是 到目前为止的研究已经调查了年龄对PCA治疗的影响。拟议的研究提供了一种新颖的、统一的 解释对ADT的PCA反应较差的机制，以及较高和较差的PCA发生率 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 在PCA结果中调节癌症种族差异。

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.