A Phase II Randomized Placebo Controlled Trial of Epigallocatechin-3-Gallate (EGCG) on Physical Frailty and Tumor Necrosis Factor-alpha and Associated Immune Markers in Older Cancer Survivors

表没食子儿茶素-3-没食子酸酯 (EGCG) 对老年癌症幸存者身体虚弱和肿瘤坏死因子-α 及相关免疫标志物的 II 期随机安慰剂对照试验

• 批准号: 10570438
• 负责人: Nikesha Gilmore
• 金额: $ 16.83万
• 依托单位: UNIVERSITY OF ROCHESTER
• 依托单位国家: 美国
• 财政年份: 2023
• 资助国家: 美国
• 起止时间: 2023-03-01 至 2028-02-29
• 项目状态: 未结题
• 来源: https://reporter.nih.gov/project-details/10570438
• 关键词: Acceleration; Address; Adherence; Adverse event; Age; Aging; Anti-Inflammatory Agents; Anxiety; Ascorbic Acid; Basic Science; Behavior Therapy; Biological; Biological Markers; Biometry; Black Populations; Black race; Cancer Control; Cancer Survivor; Catechin; Clinical Research; Clinical Trials; Collaborations; Complement; DNA Methylation; Development Plans; Dose; Elderly; Epigallocatechin Gallate; Epigenetic Process; Equity; Feasibility Studies; Functional disorder; Funding; Goals; Green tea; Immunologic Markers; Individual; Inflammation; International; Intervention; Intervention Trial; Lead; Malignant Neoplasms; Measures; Medical; Mental Depression; Mentors; Mentorship; Morbidity - disease rate; Nutraceutical; Oncology; Oral; Pathway interactions; Patients; Phase; Physical Performance; Placebos; Positioning Attribute; Preparation; Randomized; Recording of previous events; Research; Research Priority; Risk; Risk Reduction; Serum; Study Subject; Survivors; Syndrome; TNF gene; Testing; Time; Training; Translational Research; Treatment/Psychosocial Effects; Vulnerable Populations; Work; aged; arm; cancer clinical trial; cancer therapy; capsule; career development; clinical trial participant; design; disadvantaged background; equity, diversity, and inclusion; frailty; functional decline; health disparity; health equity; high risk; improved; improved outcome; innovation; mortality; novel marker; post intervention; predictive marker; psychosocial stressors; racial minority; randomized placebo controlled trial; randomized placebo-controlled clinical trial; randomized, clinical trials; research and development; skills; standard care; translational scientist

Frailty is a significant problem for older (age 65+) cancer survivors, particularly Black survivors. Older cancer survivors are at 46% greater risk of being physically frail compared to those without a history of cancer. Older Black cancer survivors are at 18% greater risk of being frail compared to older white survivors. No standard treatments for physical frailty in older cancer survivors exist. Tumor necrosis factor-α (TNF-α) and related immune markers are associated with physical frailty in older cancer survivors. Black individuals have elevated TNF-α and related immune markers due to the psychosocial stressors tied to their racially minoritized status. Epigallocatechin-3-gallate (EGCG) is a potent anti-inflammatory nutraceutical that reduces TNF-α and related immune markers and risk of functional decline. EGCG is a promising intervention to reduce physical frailty in older cancer survivors. This proposal builds upon my previous work demonstrating a relationship between cancer treatments, physical frailty, DNAmage, and TNF-α and related immune markers. My work also shows that an EGCG intervention (capsules with 800mg EGCG + 250mg VitC) is safe and feasible in older cancer survivors. This proposal presents a five-year complimentary research and career development plan. For this proposal I will conduct a Phase II, multicenter, 2-arm placebo controlled randomized clinical trial in 118 (58 Black) older cancer survivors (aged 65+), who have completed cancer treatment (≤12 months) and are at least pre-frail (Fried Frailty Score ≥2) and randomized to the EGCG intervention or placebo for 12 weeks. The aims of the proposed study are: 1) To evaluate the preliminary efficacy of the EGCG intervention on physical frailty; 2) To evaluate the preliminary efficacy of the EGCG intervention on TNF-α and related immune markers; 3) To explore if baseline TNF-α and related immune markers and DNAmage are associated with baseline and post-intervention physical frailty; and 4) To explore the efficacy of the EGCG intervention on physical frailty and TNF-α and related immune markers in older Black vs. white cancer survivors. I will also complete the following new training goals: 1) To develop expertise to design, conduct, analyze and lead multicenter randomized clinical trials focused on nutraceuticals as interventions for frailty in older cancer survivors; 2) To obtain training in epigenetics as a biomarker of frailty; 3) To gain expertise in strategies to improve the diversity of clinical trial participants, with an emphasis on older Black cancer survivors. My mentorship committee includes national and international experts in nutraceutical and behavioral interventions, geriatric oncology, translational science, biostatistics, and diversity, equity, and inclusion. Under the guidance of Drs. Michelle Janelsins and Luke Peppone (primary mentors), Dr. Supriya Mohile (co-mentor), and Drs. Charles Kamen, Paula Vertino, Michael Sohn and Ms. Canin (advisors) I will obtain essential skills that I currently do not possess. The training and research plan will position me to achieve my long-term goal to become an independently R01-funded translational scientist in geriatric oncology who develops and tests equitable and mechanistically driven, cancer control interventions.

对于老年（65 岁以上）癌症幸存者，尤其是黑人老年癌症幸存者来说，虚弱是一个重大问题。 与没有癌症病史的人相比，幸存者身体虚弱的风险高出 46%。 与老年白人癌症幸存者相比，黑人癌症幸存者虚弱的风险高出 18%。 存在针对老年癌症幸存者身体虚弱的治疗方法：肿瘤坏死因子-α (TNF-α) 及相关药物。 免疫标记物与老年癌症幸存者的身体虚弱有关。 TNF-α 和相关免疫标记物归因于与其种族少数地位相关的社会心理压力源。 表没食子儿茶素-3-没食子酸酯 (EGCG) 是一种有效的抗炎营养保健品，可减少 TNF-α 和相关物质 免疫标志物和功能下降的风险 EGCG 是一种有前途的干预措施，可以减少身体虚弱。 该提案建立在我之前证明癌症之间关系的工作的基础上。 我的工作还表明，治疗、身体虚弱、DNAmage 和 TNF-α 以及相关的免疫标记物。 EGCG 干预（胶囊含 800 毫克 EGCG + 250 毫克维生素 C）对于老年癌症幸存者来说是安全可行的。 该提案提出了一个为期五年的免费研究和职业发展计划。 对 118 名（58 名黑人）老年癌症进行 II 期、多中心、双组安慰剂对照随机临床试验 幸存者（65 岁以上），已完成癌症治疗（≤12 个月）且至少处于虚弱状态（Fried Frailty 评分≥2）并随机接受 EGCG 干预或安慰剂 12 周。 是： 1) 评估 EGCG 干预对身体虚弱的初步疗效； 2) 评估 EGCG 干预对 TNF-α 和相关免疫标志物的初步疗效 3) 探讨基线是否有效； TNF-α 和相关免疫标记物以及 DNAmage 与基线和干预后身体状况相关 4) 探讨EGCG干预对身体虚弱和TNF-α及相关免疫的功效 我还将完成以下新的培训目标：1） 培养设计、实施、分析和领导多中心随机临床试验的专业知识 营养保健品作为老年癌症幸存者虚弱的干预措施；2) 获得表观遗传学培训； 3) 获得改善临床试验参与者多样性策略的专业知识； 我的指导委员会包括国内和国际专家。 在营养保健和行为干预、老年肿瘤学、转化科学、生物统计学和多样性方面， 在 Michelle Janelsins 博士和 Luke Peppone 博士（主要导师）的指导下， Supriya Mohile（共同导师）、Charles Kamen 博士、Paula Vertino、Michael Sohn 和 Canin 女士（顾问） 将获得我目前不具备的基本技能。培训和研究计划将使我能够胜任。 实现我的长期目标，成为一名独立的 R01 资助的老年肿瘤学转化科学家 他开发并测试公平且机械驱动的癌症控制干预措施。