Interventions Targeting Inflammation for Chemotherapy-Related Cognitive Problems

针对化疗相关认知问题的炎症干预措施

• 批准号: 8508506
• 负责人: Michelle C Janelsins
• 金额: $ 14.49万
• 依托单位: UNIVERSITY OF ROCHESTER
• 依托单位国家: 美国
• 财政年份: 2013
• 资助国家: 美国
• 起止时间: 2013-04-01 至 2018-03-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/8508506
• 关键词: Adjuvant Chemotherapy; Adult; Aftercare; Anti-Inflammatory Agents; Anti-inflammatory; Area; Attention; Award; B-Lymphocytes; Basic Science; Behavioral; Behavioral Research; Biological Assay; Biometry; CCL2 gene; Cancer Control; Cancer Patient; Clinical; Clinical Research; Clinical Trials; Cognition; Cognitive; Cognitive Science; Commit; Cytokine Receptors; Data; Development; Development Plans; Disease; Education; Ensure; Environment; Etiology; Exercise; Exercise Physiology; Female Breast Carcinoma; Flow Cytometry; Foundations; Funding; Future; Goals; Health education; Home environment; Ibuprofen; Immune; Immunology; Impaired cognition; Inflammation; Inflammatory; Interleukin-1; Interleukin-10; Interleukin-6; Intervention; K-Series Research Career Programs; Knowledge; Light; Link; Malignant Neoplasms; Measurement; Measures; Mediating; Medical Oncology; Medical center; Memory; Mentors; Nerve Degeneration; Neuropsychological Tests; Neurosciences; Pathway interactions; Patient Care; Patients; Pharmaceutical Preparations; Phase; Physical activity; Pilot Projects; Placebo Control; Placebos; Positioning Attribute; Production; Public Health; Quality of life; Radiation Oncology; Randomized; Randomized Controlled Clinical Trials; Reporting; Research; Research Personnel; Resistance; Risk; Serum; TNF gene; Time; Training; Universities; Walking; Work; arm; base; cancer therapy; career; career development; cell type; chemobrain; chemotherapy; cognitive function; computerized; cytokine; design; effective therapy; executive function; experience; improved; intervention effect; malignant breast neoplasm; monocyte; neurocognitive test; neuropsychological; novel; professor; programs; public health relevance; skills; skills training; therapy development; three-arm study; visual memory

DESCRIPTION (provided by applicant): Hemotherapy-related cognitive impairment (CRCI) is a significant problem that develops in up to 75% of breast cancer patients, often persisting for many years and significantly impairing quality of life. The etiology of CRCI is not clearly understood, and there are no effective management approaches. Reduction of inflammation is a promising target to alleviate CRCI, and translational investigators well versed in clinical and behavioral research, immunology and neuroscience are needed to advance knowledge in this area. Dr. Michelle Janelsins, an Assistant Professor in the Department of Radiation Oncology at the University of Rochester Medical Center, is applying for a K07 mentored career development award to expand her clinical and behavioral research skills and to integrate new skills with her strong basic science abilities as an independent clinical and translational cancer control investigator with expertise in interventions for CRCI. This application provides Dr. Janelsins with new training and skills necessary to develop, implement, and assess interventions in a clinical setting and combine these new abilities with her established skills and knowledge in immunology and neuroscience to successfully conduct the first randomized, controlled, pilot study we are aware of investigating the influence of two novel interventions (exercise and ibuprofen) on CRCI and inflammation. Career Development Plan: Dr. Janelsins' previous training provides an outstanding initial foundation, but she needs new training in the conduct of Phase II-III clinical trials, cognitive assessment and related bio behavioral immune pathways, and exercise intervention development to become a successful independent clinical researcher with expertise in bio behavioral research focusing on understanding and alleviating CRCI. Her four career development training goals are: 1) to develop expertise in cancer control Phase II-III clinical trials, 2) to develop expertise in cognitive science and cognitive assessments and related bio behavioral immune pathways, 3) to develop expertise in exercise physiology, physical activity assessments and exercise interventions, and 4) to promote the development of an independent academic research career. Dr. Janelsins has an outstanding mentoring team: Dr. Gary Morrow, a leading cancer control researcher with NCI funding for over thirty years, is her senior mentor; Drs. Tim Ahles and Deborah Cory-Slechta provide expertise in neurocognitive testing as her co-mentors; Dr. Karen Mustian provides expertise in exercise interventions as a co-mentor; and advisors Drs. Jan Moynihan (immunology), Michelle Shayne (medical oncology), and Charles Heckler (biostatistics) provide specific expertise in key areas. Research Plan: The proposed Phase II RCT, based partially on Dr. Janelsins' preliminary data, is a three-arm study comparing the influence of ibuprofen + health education (Arm 1), placebo + exercise (Arm 2) and placebo + health education (control; Arm 3) on CRCI in 120 breast cancer patients undergoing chemotherapy experiencing CRCI. The exercise and ibuprofen arms will each be compared to the control (Arm 3) with the primary goal of assessing, analyzing, and interpreting the preliminary efficacy of each intervention in alleviating CRCI and the effects of each intervention on inflammation. This award will position Dr. Janelsins to become a leader in the cancer and cognition field who, over her career, will make meaningful contributions to patient care. Research findings will be used to design future definitive RCTs, ensure Dr. Janelsins' successful transition to an independent, R01- funded, clinical and translational investigator, and ultimately reduce the public health burden from CRCI.

描述（由申请人提供）：与血液治疗相关的认知障碍 (CRCI) 是一个严重问题，高达 75% 的乳腺癌患者会出现这种问题，通常会持续多年，并严重损害生活质量。 CRCI的病因尚不清楚，也没有有效的治疗方法。减少炎症是缓解 CRCI 的一个有希望的目标，需要精通临床和行为研究、免疫学和神经科学的转化研究人员来推进这一领域的知识。罗切斯特大学医学中心放射肿瘤学系助理教授 Michelle Janelsins 博士正在申请 K07 指导职业发展奖，以扩展她的临床和行为研究技能，并将新技能与她强大的基础科学能力相结合作为一名独立的临床和转化癌症控制研究者，拥有 CRCI 干预方面的专业知识。该应用程序为 Janelsins 博士提供了 在临床环境中制定、实施和评估干预措施所需的新培训和技能，并将这些新能力与她在免疫学和神经科学方面已建立的技能和知识相结合，以成功进行我们所知的第一个随机、对照、试点研究，调查影响两种新的干预措施（运动和布洛芬）对 CRCI 和炎症的影响。职业发展计划：Janelins 博士之前的培训提供了出色的初始基础，但她需要在进行 II-III 期临床试验、认知评估和相关生物行为免疫途径以及运动干预开发方面接受新的培训，才能成为一名成功的独立专家具有生物行为研究专业知识的临床研究员，专注于理解和减轻 CRCI。她的四个职业发展培训目标是：1）发展癌症控制II-III期临床试验方面的专业知识，2）发展认知科学和认知评估以及相关生物行为免疫途径方面的专业知识，3）发展运动生理学方面的专业知识，身体活动评估和运动干预，以及4）促进独立学术研究事业的发展。 Janelsins博士拥有一支优秀的导师团队：她的高级导师是获得NCI资助三十多年的顶尖癌症控制研究员Gary Morrow博士；博士。 Tim Ahles 和 Deborah Cory-Slechta 作为她的共同导师提供神经认知测试方面的专业知识； Karen Mustian 博士作为联合导师提供运动干预方面的专业知识；和顾问博士。 Jan Moynihan（免疫学）、Michelle Shayne（肿瘤医学）和 Charles Heckler（生物统计学）提供关键领域的具体专业知识。研究计划：拟议的二期随机对照试验部分基于 Janelsins 博士的初步数据，是一项三组研究，比较布洛芬 + 健康教育（第 1 组）、安慰剂 + 运动（第 2 组）和安慰剂 + 健康教育的影响（对照；第 3 组）对 120 名接受化疗且经历 CRCI 的乳腺癌患者进行 CRCI 治疗。运动组和布洛芬组将分别与对照组（第 3 组）进行比较，主要目标是评估、分析和解释每种干预措施在缓解 CRCI 方面的初步功效以及每种干预措施对炎症的影响。该奖项将使 Janelsins 博士成为癌症和认知领域的领导者，在她的职业生涯中，她将为患者护理做出有意义的贡献。研究结果将用于设计未来的最终随机对照试验，确保 Janelsins 博士成功转型为独立的、R01 资助的临床和转化研究者，并最终减轻 CRCI 带来的公共卫生负担。