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

• 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
• 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

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.

项目摘要 概述。化学疗法诱导的周围神经病（CIPN）是NCI的高优先研究领域 它的高流行，严重性和缺乏既定治疗方法。 CIPN患者患麻木和 他们的手和脚上的神经性疼痛，尤其是由于冷刺激。虽然毒品尚未证明 成功治疗CIPN，我们的初步数据表明，化学疗法中的6周运动 减少患者报告的CIPN症状（麻木/刺痛）。锻炼可能由于其宽度而有效 对CIPN病因的多种途径的影响，包括感染和大脑。我们的小说 理论框架提案，即化学疗法部分通过慢性炎症引起CIPN症状 并破坏大脑从身体中的感觉处理（Interoception）。如果我们的理论正确， 将来的干预措施可以量身定制，以标准化注射和拦截，作为全面的一部分 CIPN的治疗计划。该申请使用练习V的12周II期随机临床试验。 营养教育（控制）评估CIPN运动的初步效率。 职业发展计划。 Kleckner博士具有研究感知性脑电路的经验，并且具有 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 运动以改善癌症治疗（例如CIPN）的毒性，他需要（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措施， 特别是运动，（3）研究和治疗CIPN及其病因，特别是炎症和大脑， （4）作为独立研究者纳入肿瘤学和症状管理。克莱克纳博士 指导团队在这些领域具有专业知识，URMC的环境是世界一流的癌症控制。 研究计划。八十名乳腺癌妇女（非转移性，即将接受紫杉烷化疗， 试验期间没有辐射或手术）将随机分配到12周的：ARM 1，标准护理加上 运动或手臂2：标准护理加营养教育（控制）。既定的运动干预 （ixcap©®）由Mustian博士（Mentor）开发，涉及面对面的指导和处方的处方 家庭渐进式步行和抵抗运动计划。营养教育（控制）涉及相等的时间 并注意运动臂，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，创新和临床评估 干预前，干预后和干预后3个月进行拦截。 影响。克莱克纳博士将获得成为独立研究人员所需的关键培训，并将 数据支持未来的R01赠款研究CIPN。这项工作将提供对影响的宝贵见解 在CIPN上进行锻炼，并将探索其与目前已知的两种生物学途径的关系 - 炎症和互感。这项工作尤其重要，因为CIPN没有有效的治疗方法。

项目成果

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
• 作者: Stoller,Stefanie;Capozza,Scott;Alberti,Paola;Lustberg,Maryam;Kleckner,IanR
• 通讯作者: Kleckner,IanR

Updated systematic review of the effects of exercise on understudied health outcomes in cancer survivors.

• DOI: 10.1002/cam4.6753
• 发表时间: 2023-12
• 期刊: Cancer medicine
• 影响因子: 4

Conscious awareness is necessary for affective faces to influence social judgments.

情感面孔要影响社会判断，有意识的认识是必要的。

• DOI: 10.1016/j.jesp.2018.07.013
• 发表时间: 2018
• 期刊: Journal of experimental social psychology
• 影响因子: 3.5
• 作者: Kleckner,IanR;Anderson,EricC;Betz,NicoleJ;Wormwood,JolieB;EskewJr,RheaT;Barrett,LisaFeldman
• 通讯作者: Barrett,LisaFeldman