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: 10684640
• 负责人: Ian Robert Kleckner
• 金额: $ 17.7万
• 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/10684640
• 关键词: Affect; Attention; Awareness; Behavioral; Body Image; Books; Brain; Chemotherapy-induced peripheral neuropathy; Clinical assessments; Consent; Data; Development; Dose Limiting; Eating; Educational process of instructing; Exercise; Exercise Therapy; 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; Phase; Physiological; Placebos; Platinum; Play; Process; Questionnaires; Randomized; Randomized, Controlled Trials; Reporting; Research; Role; Sensory; Serum; Severities; Sterile coverings; Symptoms; System; Tactile; Testing; Thalamic structure; Time; Toxic effect; Walking; Work; Writing; anakinra; bodily sensation; cancer therapy; chemotherapy; comparison control; cytokine; effective intervention; effective therapy; experience; follow-up; foot; improved; innovation; malignant breast neoplasm; member; mortality; neural; neurotoxic; nutrition; nutrition education; peripheral nerve damage; prevent; randomized, clinical trials; 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 化学疗法诱导的周围神经病（CIPN）是一种严重的剂量限制毒性，影响超过65％ 接受基于铂基化学疗法的胃肠癌癌症的患者。不仅CIPN增加 通过限制化学疗法的剂量，CIPN的死亡率会影响步行，写作，进食和通过麻木的敷料， 刺痛，疼痛，敏感性和手脚痉挛。没有FDA批准的治疗方法 CIPN是因为我们需要对CIPN的病理生理和作用机理有更深入的了解 CIPN的有希望的治疗方法。此外，大多数对人类CIPN的研究都集中在基于紫杉烷的基于紫杉烷的研究上 乳腺癌患者的化学疗法。在这里，我们专注于患者的基于铂的化学疗法 与胃肠道癌一起使用，因为紫杉烷和铂诱导的CIPN都很普遍，但表现出 毒性的不同体征，症状和机制，可能对给定治疗的反应不同。这 项目的动机是一种创新的观点，即CIPN症状不仅归因于周围神经 损坏，而是通过对感官间脑系统的损坏来恶化CIPN符号 从身体以及全身注射中引起感觉。 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，拦截和炎症进行化学疗法。具体 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）截距（功能性 感官间脑系统和自我报告中的连通性）和（4）炎症（血清炎症 细胞因子）。 这是检查铂化疗期间运动对CIPN的影响并检查的第一项研究 拦截和注射在铂诱导的CIPN治疗中的作用。这项研究的结果将 告知R01应用程序，以更明确地评估这一CIPN和运动理论。如果这项工作成功， 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（即拦截和炎症）。我们相信这种知识 可以使用练习或其他 影响这些途径的干预措施。这最终将有助于减轻化学治疗的燃烧 癌症患者。