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The Effects of Exercise on Chemotherapy-Induced Peripheral Neuropathy, Inflammation, and Interoceptive Brain Circuitry

运动对化疗引起的周围神经病变、炎症和内感受脑回路的影响

基本信息

批准号：
10437850
负责人：
Ian Robert Kleckner
金额：
$ 11.81万
依托单位：
UNIVERSITY OF MARYLAND BALTIMORE
依托单位国家：
美国
项目类别：
财政年份：
2018
资助国家：
美国
起止时间：
2018-07-06 至 2024-06-30
项目状态：
已结题

来源：
https://reporter.nih.gov/project-details/10437850
关键词：
Activities of Daily Living Area Attention Behavior Therapy Behavioral Biological Body part Books Brain Breast Cancer Patient Cancer Control Cancer Patient Cancer and Nutrition Chemotherapy-Oncologic Procedure Chemotherapy-induced peripheral neuropathy Chronic Clinic Clinical Clinical assessments Conduct Clinical Trials Consent Data Detection Development Development Plans Diabetic Neuropathies Dose Dose-Limiting Eating Educational workshop Environment Enzyme-Linked Immunosorbent Assay Esthesia Etiology Exercise Female Breast Carcinoma Future Goals Grant Hand Heart High Prevalence Home Human Hyperactivity IL8 gene Impairment Inflammation Instruction Interleukin-1 beta Interleukin-10 Interleukin-6 Interoception Intervention Knowledge Measures Mentors Nervous System Trauma Neuraxis Neurons Neuropathy Nonmetastatic Numbness Oncology Operative Surgical Procedures Pain Pamphlets Pathway interactions Patients Perception Pharmaceutical Preparations Phase Physical activity Placebos Platinum Process Radiation Randomized Randomized Clinical Trials Reporting Research Research Personnel Research Priority Rodent Sensory Serum Severities Symptoms Tactile Testing Time Toxic effect Training Training Activity Vinca Alkaloids Walking Woman Work anakinra arm base brain circuitry cancer therapy career career development chemotherapy clinically significant design effective intervention effective therapy exercise intervention exercise prescription exercise program experience foot human study improved innovation insight malignant breast neoplasm meetings member mortality novel nutrition nutrition education painful neuropathy post intervention prevent primary outcome public health relevance resistance exercise secondary analysis standard care symposium symptom management taxane theories translational scientist treatment planning

项目摘要

PROJECT SUMMARY Overview. Chemotherapy-induced peripheral neuropathy (CIPN) is a high-priority research area for NCI given its high prevalence, severity, and lack of established treatments. Patients with CIPN suffer from numbness and neuropathic pain in their hands and feet, especially from cold stimulation. Although drugs have not proven successful for treating CIPN, our preliminary data suggest that 6 weeks of exercise during chemotherapy reduces patient-reported CIPN symptoms (numbness/tingling). Exercise may be effective due to its widespread effects on multiple pathways involved in the etiology of CIPN, including inflammation and the brain. Our novel theoretical framework proposes that chemotherapy causes CIPN symptoms partly via chronic inflammation and by disrupting the brain’s processing of sensations from the body (interoception). If our theory is correct, future interventions can be tailored to normalize inflammation and interoception as part of a comprehensive treatment plan for CIPN. This application uses a 12-week phase II randomized clinical trial of exercise vs. nutrition education (control) to assess the preliminary efficacy of exercise on CIPN. Career Development Plan. Dr. Kleckner has experience studying interoceptive brain circuitry, and has recently begun studying cancer control and CIPN. To become an independent investigator studying and using exercise to ameliorate toxicities from cancer treatment, such as CIPN, he needs training in (1) designing and conducting clinical trials with cancer patients, (2) designing and conducting behavioral interventions, specifically exercise, (3) studying and treating CIPN and its etiology, specifically inflammation and the brain, and (4) integrating into oncology and symptom management as an independent investigator. Dr. Kleckner’s mentoring team has expertise in these areas and the environment at URMC is world-class for cancer control. Research Plan. Eighty women with breast cancer (non-metastatic, about to receive taxane chemotherapy, and no radiation or surgery during the trial) will be randomly assigned to 12 weeks of: Arm 1, standard care plus exercise or Arm 2: standard care plus nutrition education (control). The established exercise intervention (EXCAP©®), developed by Dr. Mustian (mentor), involves face-to-face instruction and a prescription for an at- home progressive walking and resistance exercise program. Nutrition education (control) involves equal time and attention as the exercise arm, but covers nutrition for cancer patients and lacks an exercise prescription. Measures include patient-reported CIPN symptoms, and clinical assessments of CIPN, inflammation, and interoception at pre-intervention, post-intervention, and 3 months post-intervention. Impact. Dr. Kleckner will obtain critical training required to become an independent researcher and will have data to support a future R01 grant studying CIPN. This work will provide valuable insight into the effects of exercise on CIPN and will explore its relationship with two currently understudied biological pathways— inflammation and interoception. This work is particularly important because CIPN has no effective treatments.

项目概要概述。化疗引起的周围神经病变 (CIPN) 是 NCI 的一个高度优先的研究领域其患病率高、严重且缺乏既定治疗方法。 CIPN 患者会出现麻木和手脚神经性疼痛，尤其是冷刺激引起的疼痛。虽然药物尚未证明成功治疗 CIPN，我们的初步数据表明化疗期间进行 6 周的运动减少患者报告的 CIPN 症状（麻木/刺痛）。锻炼可能是有效的，因为它广泛存在对 CIPN 病因学涉及的多种途径的影响，包括炎症和大脑。我们的小说理论框架提出化疗部分通过慢性炎症引起 CIPN 症状以及扰乱大脑对身体感觉的处理（内感受）。如果我们的理论是正确的未来的干预措施可以量身定制，使炎症和内感受正常化，作为综合治疗的一部分 CIPN 的治疗计划。该应用程序使用一项为期 12 周的 II 期随机临床试验，比较运动与运动。营养教育（对照）评估运动对CIPN的初步疗效。职业发展计划。 Kleckner 博士拥有研究内感受大脑回路的经验，并且最近开始研究癌症控制和 CIPN。成为一名独立研究者，研究和使用锻炼以改善癌症治疗（例如 CIPN）的毒性，他需要以下方面的培训：（1）设计和对癌症患者进行临床试验，(2) 设计和进行行为干预， (3) 研究和治疗 CIPN 及其病因，特别是炎症和大脑， (4) 作为独立研究者融入肿瘤学和症状管理。克莱克纳博士的导师团队在这些领域拥有专业知识，URMC 的癌症控制环境是世界一流的。研究计划。八十名患有乳腺癌的女性（非转移性，即将接受紫杉烷化疗，并且试验期间没有放射或手术）将被随机分配到 12 周：第 1 组，标准护理加锻炼或第 2 组：标准护理加营养教育（对照）。既定的运动干预 (EXCAP©®)，由 Mustian 博士（导师）开发，涉及面对面指导和处方。家庭渐进式步行和阻力锻炼计划。营养教育（控制）涉及同等时间和作为运动手臂的关注，但涵盖了癌症患者的营养，并且缺乏运动处方。措施包括患者报告的 CIPN 症状以及 CIPN、炎症和疾病的临床评估干预前、干预后和干预后 3 个月的内感受。影响。 Kleckner 博士将获得成为一名独立研究员所需的关键培训，并将拥有数据支持未来研究 CIPN 的 R01 拨款。这项工作将为了解其影响提供有价值的见解 CIPN 上的练习并将探讨其与目前正在研究的两个生物途径的关系—— 炎症和内感受。这项工作尤为重要，因为 CIPN 尚无有效的治疗方法。

项目成果

期刊论文数量（18）

专著数量（0）

科研奖励数量（0）

会议论文数量（0）

专利数量（0）

Longitudinal study of inflammatory, behavioral, clinical, and psychosocial risk factors for chemotherapy-induced peripheral neuropathy.

DOI：
10.1007/s10549-021-06304-6
发表时间：
2021-09
期刊：
Breast cancer research and treatment
影响因子：
3.8
作者：
Kleckner IR;Jusko TA;Culakova E;Chung K;Kleckner AS;Asare M;Inglis JE;Loh KP;Peppone LJ;Miller J;Melnik M;Kasbari S;Ossip D;Mustian KM
通讯作者：
Mustian KM

Mechanisms, Mediators, and Moderators of the Effects of Exercise on Chemotherapy-Induced Peripheral Neuropathy.

DOI：
10.3390/cancers14051224
发表时间：
2022-02-26
期刊：
Cancers
影响因子：
5.2
作者：
Chung KH;Park SB;Streckmann F;Wiskemann J;Mohile N;Kleckner AS;Colloca L;Dorsey SG;Kleckner IR
通讯作者：
Kleckner IR

Framework to leverage physical therapists for the assessment and treatment of chemotherapy-induced peripheral neurotoxicity (CIPN).

利用物理治疗师评估和治疗化疗引起的周围神经毒性 (CIPN) 的框架。

DOI：
10.1007/s00520-023-07734-2
发表时间：
2023
期刊：
Supportive care in cancer : official journal of the Multinational Association of Supportive Care in Cancer
影响因子：
0
作者：
Stoller,Stefanie;Capozza,Scott;Alberti,Paola;Lustberg,Maryam;Kleckner,IanR
通讯作者：
Kleckner,IanR

The association between cancer-related fatigue and diabetes from pre-chemotherapy to 6 months post-chemotherapy.