High Intensity Interval Training: Optimizing Exercise Therapy to Mitigate Cardiovascular Disease Risk Following Breast Cancer Chemotherapy

高强度间歇训练：优化运动疗法以降低乳腺癌化疗后的心血管疾病风险

• 批准号: 10667675
• 负责人: Demetra Christou
• 金额: $ 22.88万
• 依托单位: UNIVERSITY OF FLORIDA
• 依托单位国家: 美国
• 财政年份: 2023
• 资助国家: 美国
• 起止时间: 2023-06-01 至 2025-05-31
• 项目状态: 未结题
• 来源: https://reporter.nih.gov/project-details/10667675
• 关键词: Acceleration; Acute; Address; Adherence; Aerobic Exercise; Age; Age Years; Aging; Apoptosis; Attention; Biological Markers; Blood; Breast Cancer Risk Factor; Breast Cancer Treatment; Breast Cancer survivor; Cardiac; Cardiovascular Diseases; Cardiovascular system; Cessation of life; Chemotherapy-Oncologic Procedure; Clinical; Clinical Trials; Compensation; Coronary Arteriosclerosis; Data; Development; Diagnosis; Echocardiography; Elderly; Endothelial Cells; Endothelium; Equilibrium; Exercise; Exercise Therapy; Fatigue; Foundations; Functional disorder; Future; Harvest; Heart failure; Injury; Interval training; Intervention; Limb structure; Lower Extremity; Mediating; Muscle Weakness; Myocardial; Non-Insulin-Dependent Diabetes Mellitus; Nonmetastatic; Participant; Pathway interactions; Patients; Peripheral Nervous System Diseases; Pilot Projects; Population; Randomized; Randomized Controlled Clinical Trials; Randomized, Controlled Trials; Recommendation; Research; Resolution; Risk; Supervision; Techniques; Time; Toxic effect; Training; Treatment-Related Cancer; Ultrasonography; Upper Extremity; Woman; Work; age related; brachial artery; breast cancer diagnosis; cardiovascular disorder prevention; cardiovascular disorder risk; chemotherapy; design; effective therapy; equilibration disorder; evidence base; exercise intervention; exercise prescription; exercise regimen; exercise training; fall risk; frailty; heart function; human old age (65+); improved; innovation; insight; malignant breast neoplasm; minimally invasive; novel; premature; prevent; side effect; success; treatment as usual

PROJECT SUMMARY Aging is a major risk factor for breast cancer and 80% of breast cancer cases are diagnosed after age 50. Currently in the US, there are more than 3.8 million breast cancer survivors, and this number is expected to increase dramatically due to the aging of the population. Chemotherapy is a highly effective treatment for breast cancer but is associated with acute and long-term cardiovascular toxicity that may accelerate cardiovascular aging, thus setting the stage for premature development of cardiovascular disease (CVD). Aerobic exercise is recommended for CVD prevention, however, evidence on the optimal exercise prescription in breast cancer survivors is limited. Breast cancer survivors often suffer from long-lasting cancer therapy-related side effects (e.g., physical dysfunction, severe fatigue, muscle weakness, peripheral neuropathy, and balance impairments) that may be compounded by age-related frailty and mobility issues (50% of breast cancer survivors are older than age 60). These unique challenges may limit exercise feasibility, adherence, and in turn efficacy. High- intensity interval training (HIIT) is attracting increasing attention as a time-efficient and potentially superior aerobic exercise strategy for CVD prevention compared to moderate-intensity continuous training (MICT) in clinical populations. We have recently adapted HIIT and MICT on an all-extremity non-weight-bearing exercise (ANE) ergometer that eliminates balance concerns and distributes work between the upper and lower extremities, compensating for weakness and fatigue. Our HIIT-ANE and MICT-ANE regimens are novel and innovative exercise interventions for breast cancer survivors. Our central hypothesis is that HIIT-ANE will result in greater and more durable improvements in endothelial and cardiac function compared with MICT-ANE and usual care (UC) in breast cancer survivors who have recently completed chemotherapy. The aims of this application are to conduct a randomized controlled trial to investigate: 1) the short-term and prolonged effects of HIIT-ANE, MICT-ANE and UC on endothelial and cardiac function; and 2) the durability of the endothelial and cardiac effects of HIIT-ANE vs. MICT-ANE. Women, 50 years of age and older, who have completed chemotherapy within the past 6 months for primary, invasive, non-metastatic, stage I-III breast cancer will be randomized to 1 of 3 groups: HIIT-ANE, MICT-ANE or UC. Exercise training will be performed 3 days/week over 12 weeks under supervision. The primary focus will be on endothelial and cardiac function assessed by flow- mediated dilation and global longitudinal strain, respectively. Assessments will be performed at baseline, after the 12-week exercise intervention and after a 12-week observation period. To gain mechanistic insight, we will investigate circulating blood biomarkers and key biomarkers in endothelial cells harvested using a state-of-the- art endovascular technique. This exploratory/developmental R21 will provide early evidence on whether our promising HIIT-ANE is more effective in mitigating CVD risk than MICT-ANE and UC following breast cancer chemotherapy. Our findings will lay the foundation for designing a rigorous full-scale clinical trial.

项目概要 衰老是乳腺癌的主要危险因素，80% 的乳腺癌病例是在 50 岁之后确诊的。 目前在美国，有超过 380 万乳腺癌幸存者，预计这一数字将 由于人口老龄化而急剧增加。化疗是一种非常有效的乳腺治疗方法 癌症，但与急性和长期心血管毒性有关，可能会加速心血管疾病 衰老，从而为心血管疾病（CVD）的过早发展奠定了基础。有氧运动是 推荐用于预防心血管疾病，但是，关于乳腺癌最佳运动处方的证据 幸存者有限。乳腺癌幸存者经常遭受与癌症治疗相关的长期副作用 （例如身体功能障碍、严重疲劳、肌肉无力、周围神经病变和平衡障碍） 与年龄相关的虚弱和活动能力问题可能会加剧这种情况（50% 的乳腺癌幸存者年龄较大） 超过 60 岁）。这些独特的挑战可能会限制锻炼的可行性、依从性，进而限制锻炼的有效性。高的- 强度间歇训练 (HIIT) 作为一种省时且具有潜在优越性的训练方法正受到越来越多的关注 预防 CVD 的有氧运动策略与中等强度持续训练 (MICT) 的比较 临床人群。我们最近将 HIIT 和 MICT 应用于全肢非负重锻炼 (ANE) 测力计，消除平衡问题并在上、下之间分配工作 四肢，补偿虚弱和疲劳。我们的 HIIT-ANE 和 MICT-ANE 疗法新颖且 针对乳腺癌幸存者的创新运动干预措施。我们的中心假设是 HIIT-ANE 会导致 与 MICT-ANE 相比，内皮和心脏功能得到更大、更持久的改善 最近完成化疗的乳腺癌幸存者的常规护理（UC）。本次活动的目的 申请将进行随机对照试验来调查：1）短期和长期影响 HIIT-ANE、MICT-ANE 和 UC 对内皮和心脏功能的影响； 2）内皮细胞的耐久性和 HIIT-ANE 与 MICT-ANE 的心脏影响。 50岁及以上的女性，已完成 过去 6 个月内对原发性、侵袭性、非转移性 I-III 期乳腺癌进行过化疗 随机分为 3 组中的一组：HIIT-ANE、MICT-ANE 或 UC。每周进行3天的运动训练 12周的监督下。主要重点是通过血流评估的内皮和心脏功能 分别介导的扩张和整体纵向应变。评估将在基线后进行 12 周的运动干预和 12 周的观察期后。为了获得机械洞察力，我们将 研究循环血液生物标志物和使用最新技术收获的内皮细胞中的关键生物标志物 艺术血管内技术。这个探索性/发展性的 R21 将提供早期证据，证明我们是否 有前途的 HIIT-ANE 在降低乳腺癌风险方面比 MICT-ANE 和 UC 更有效 化疗。我们的研究结果将为设计严格的全面临床试验奠定基础。