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.

虚弱是老年（65岁以上）癌症幸存者的一个重要问题，特别是黑人幸存者。年纪较大的癌症 与没有癌症史的人相比，幸存者身体虚弱的风险高出46%。老年 与年长的白色幸存者相比，黑人癌症幸存者身体虚弱的风险高出18%。没有标准 存在对老年癌症幸存者身体虚弱的治疗。肿瘤坏死因子-α（TNF-α）及相关 免疫标记物与老年癌症幸存者的身体虚弱有关。黑人的人数增加了 TNF-α和相关的免疫标记物，由于心理社会压力与他们的种族少数地位有关。 表没食子儿茶素-3-没食子酸酯（EGCG）是一种有效的抗炎营养品，可降低TNF-α和相关 免疫标记和功能下降的风险。表没食子儿茶素没食子酸酯是一种有希望的干预措施，以减少身体虚弱， 老年癌症幸存者这个建议建立在我以前的工作基础上，证明了癌症和癌症之间的关系。 治疗、身体虚弱、DNA损伤、TNF-α和相关免疫标志物。我的研究还表明， EGCG干预（含800 mg EGCG +250 mg VitC的胶囊）在老年癌症幸存者中是安全可行的。 该提案提出了一项为期五年的免费研究和职业发展计划。对于这个提议，我将 在118例（58例黑人）老年癌症患者中开展一项II期、多中心、2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），至少处于虚弱前期（Fried Frailty 评分≥2），并随机分配至EGCG干预组或安慰剂组12周。拟议研究的目的 分别是：1）评估表没食子酸没食子酸酯（EGCG）干预对身体虚弱的初步疗效; 2）评估 表没食子儿茶素没食子酸酯干预对TNF-α和相关免疫标志物的初步疗效; 3）探索基线 TNF-α和相关的免疫标志物以及DNA标记物与基线和干预后的身体状况相关。 探讨EGCG干预对体质虚弱、TNF-α及相关免疫功能的影响 在老年黑人和白色癌症幸存者中的标志物。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的策略方面的专业知识， 重点关注老年黑人癌症幸存者我的导师委员会包括国内和国际专家 在营养和行为干预，老年肿瘤学，转化科学，生物统计学，和多样性， 公平和包容。在Michelle Janelsins博士和Luke Pepperson博士（主要导师）的指导下， Supriya Mohile（共同导师）和Charles Kamen博士、Paula Vertino博士、Michael Sohn博士和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 实现我的长期目标，成为一名独立的R 01资助的老年肿瘤学转化科学家 世卫组织制定和测试公平和机械驱动的癌症控制干预措施。