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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.

项目总结

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 Effects of a Mediterranean Diet Intervention on Cancer-Related Fatigue for Patients Undergoing Chemotherapy: A Pilot Randomized Controlled Trial.