Effects of exercise during platinum chemotherapy on neuropathy: examining the interoceptive brain system and inflammation

铂类化疗期间运动对神经病变的影响：检查大脑内感受系统和炎症

• 批准号: 10355322
• 负责人: Ian Robert Kleckner
• 金额: $ 21.67万
• 依托单位: UNIVERSITY OF MARYLAND BALTIMORE
• 依托单位国家: 美国
• 财政年份: 2022
• 资助国家: 美国
• 起止时间: 2022-09-01 至 2024-08-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/10355322
• 关键词: Affect; Attention; Awareness; Behavioral; Books; Brain; Chemotherapy-induced peripheral neuropathy; Clinical assessments; Consent; Data; Development; Dose-Limiting; Eating; Educational process of instructing; Encephalitis; Esthesia; Exercise; Exhibits; FDA approved; Functional Magnetic Resonance Imaging; Functional disorder; Hand; Home; Human; IL8 gene; Inflammation; Inflammatory; Insula of Reil; Interleukin-1 beta; Interleukin-10; Interleukin-6; Interoception; Intervention; Knowledge; Learning; Malignant Neoplasms; Malignant neoplasm of gastrointestinal tract; Measures; Muscle Cramp; Neuropathy; Numbness; Pain; Pamphlets; Pathway interactions; Patient Self-Report; Patient risk; Patients; Perception; Phase; Physiological; Placebos; Platinum; Play; Process; Randomized; Randomized Clinical Trials; Randomized Controlled Trials; Reporting; Research; Role; Sensory; Serum; Severities; Signs and Symptoms; Sterile coverings; Symptoms; System; Tactile; Testing; Thalamic structure; Time; Toxic effect; Walking; Work; Writing; anakinra; arm; base; bodily sensation; cancer therapy; chemotherapy; cytokine; effective intervention; effective therapy; experience; follow-up; foot; improved; innovation; malignant breast neoplasm; member; mortality; neurotoxic; nutrition; nutrition education; pain sensitivity; peripheral nerve damage; prevent; relating to nervous system; resistance exercise; systemic inflammatory response; taxane; theories

PROJECT SUMMARY/ABSTRACT Chemotherapy-induced peripheral neuropathy (CIPN) is a severe dose-limiting toxicity that affects over 65% of patients receiving platinum-based chemotherapy for gastrointestinal cancers. Not only does CIPN increase mortality by limiting the dose of chemotherapy, CIPN affects walking, writing, eating, and dressing via numbness, tingling, pain, cold sensitivity, and cramping in the hands and feet. There are no FDA-approved treatments for CIPN because we need a greater understanding of the pathophysiology of CIPN and mechanisms of action of promising treatments for CIPN. In addition, most research on CIPN in humans has focused on taxane-based chemotherapy in patients with breast cancer. Here, we are focusing on platinum-based chemotherapy in patients with gastrointestinal cancers because taxane- and platinum-induced CIPN are both very common but exhibit distinct signs, symptoms, and mechanisms of toxicities, and may respond differently to a given treatment. This project is motivated by an innovative perspective that CIPN symptoms are not due simply to peripheral nerve damage, but rather that CIPN symptoms are worsened by damage to the interoceptive brain system—which processes sensations from the body—as well as systemic inflammation. This is a Phase II randomized clinical trial to assess the effects of 12 weeks of exercise during platinum chemotherapy on CIPN, interoception, and inflammation in 60 patients with gastrointestinal cancer. The specific aims of this project are to assess the effects of exercise vs. nutrition education (control) on: (1) patient reported CIPN, (2) clinical assessments of CIPN (tactile sensitivity and cold-induced pain), (3) interoception (functional connectivity in the interoceptive brain system and self-report), and (4) inflammation (serum inflammatory cytokines). This is the first study to examine the effects of exercise during platinum chemotherapy on CIPN and to examine roles of interoception and inflammation in the treatment of platinum-induced CIPN. Results from this study will inform an R01 application to more definitively assess this theory of CIPN and exercise. If this work is successful, we will have identified an effective intervention (exercise) for alleviating CIPN and we will have a better understanding of how exercise alleviates CIPN (i.e., interoception and inflammation). We believe this knowledge can be applied to improve prediction, tracking, sub-typing, and treatment of CIPN using exercise or other interventions that affect these pathways. This will ultimately help alleviate the burden of chemotherapy on treating patients with cancer.

项目摘要/摘要 化学疗法引起的周围神经病（CIPN）是一种严重的限制性毒性，超过65％ 接受铂基化学疗法的胃癌的患者。 通过化学疗法的剂量限制死亡率，CIPN会影响步行，写作，饮食和穿衣服，通过麻木 刺痛，疼痛，敏感性和手脚痉挛。 CIPN是因为我们需要对CIPN的病理生理和作用机制有更深入的了解 其他关于CIPN的有希望的治疗方法。 乳腺癌患者的化学疗法。 与胃肠道癌一起使用，因为紫杉烷和platiced cipn都是bery bery普通的，但展示了 毒性的独特迹象，症状和机制，可能会对给定的治疗做出反应 项目的动机是一种动力的观点，即CIPN症状不仅仅是外周神经 损害，而是通过对互感的大脑系统的损害来恶化CIPN症状 - 这 从身体和系统性炎症中引起感觉。 这是一项II期随机临床试验，以评估铂期间12周运动的影响 60例胃肠道癌患者的CIPN，相互作用和炎症 该项目的目的是评估运动与营养教育（控制）的影响：（1）患者报告 CIPN，（2）CIPN的临床评估（触觉灵敏度和冷诱导的疼痛），（3）相互作用（功能） 感知性大脑系统和自我报告中的连通性）和（4）炎症（4）炎症 细胞因子）。 这是检查CIPN铂化学疗法期间运动锻炼的第一项研究，并检查 互感和炎症在铂诱导的CIPN治疗中的作用。 告知R01申请以进行更确定的评估评估。 我们将确定一种有效的干预（锻炼）来减轻CIPN，我们将有更好的 了解运动如何减轻CIPN（即相互作用和炎症）。 可以使用练习或其他 感受道路的干预措施最终将有助于Allp Allp Allp Allp Allp化学疗法治疗。 癌症患者。