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）癌症存活，尤其是黑人存活的脆弱问题。较老的癌症 与没有癌症史的幸存者相比，幸存者的身体脆弱风险高46％。年龄较大 与较老的白人存活相比，黑色癌症存活率的风险高18％。没有标准 肿瘤坏死因子-α（TNF-α）及其相关 免疫标记与较老的癌症存活中的身体虚弱有关。黑人人提高了 TNF-α和相关的免疫标志物是由于与种族少量状态相关的社会心理压力引起的。 Epigallocatechin-3-Gallate（EGCG）是一种潜在的抗炎营养，可降低TNF-α及其相关 免疫标记和功能下降的风险。 EGCG是减少身体脆弱的承诺干预措施 较旧的癌症存活。这项建议是基于我以前的工作，证明了癌症之间的关系 治疗，身体脆弱，傻瓜和TNF-α和相关的免疫标记物。我的工作也表明 EGCG干预（具有800mg EGCG + 250mg VITC的胶囊）在较旧的癌症存活中是安全且可行的。 该提案提出了一项为期五年的免费研究和职业发展计划。对于这个建议，我将 在118（58个黑色）癌症中进行II期，多中心，2臂安慰剂控制的随机临床试验 幸存者（65岁以上），已经完成癌症治疗（≤12个月），至少是果园（油炸脆弱） 得分≥2），并随机分配到EGCG干预措施或安慰剂12周。拟议研究的目的 为：1）评估EGCG干预对身体脆弱的初步效果； 2）评估 EGCG干预TNF-α和相关免疫标记的初步效率； 3）探索是否基线 TNF-α和相关的免疫标志物和damage剂与基线和干预后物理有关 脆弱； 4）探索EGCG干预对物理脆弱和TNF-α和相关免疫的效率 旧黑人与白色癌症存活的标记。我还将完成以下新的培训目标：1） 开发专业知识来设计，进行，分析和领导多中心随机临床试验，重点是 营养素作为老年癌症生存中脆弱的干预措施； 2）获得表观遗传学的培训 脆弱的生物标志物； 3）在提高临床试验参与者多样性的策略方面获得专业知识， 强调较老的黑色癌症存活。我的攻击委员会包括国家和国际专家 在营养和行为干预措施中，老年肿瘤学，转化科学，生物统计学和多样性， 公平和包容。在博士的指导下。 Michelle Janelsins和Luke Peppone（主要导师），博士 supriya mohile（联合主管）和博士。查尔斯·卡门（Charles Kamen），宝拉·维尔蒂诺（Paula Vertino），迈克尔·索恩（Michael Sohn）和坎宁女士（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适应 实现我的长期目标，成为一名独立的R01资助的老年肿瘤科学家 谁开发和测试公平且机械驱动的癌症控制干预措施。