RE-ENERGIZE FONTAN - RandomizEd Exercise INtERvention desiGned to MaximIZE Fitness in Pediatric FONTAN patients

重新激活 FONTAN - 随机运动干预旨在最大限度地提高儿童 FONTAN 患者的健康状况

• 批准号: 9893292
• 负责人: Daniel Bernstein
• 金额: $ 75.27万
• 依托单位: STANFORD UNIVERSITY
• 依托单位国家: 美国
• 财政年份: 2020
• 资助国家: 美国
• 起止时间: 2020-03-10 至 2021-02-28
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/9893292
• 关键词: 19 year old; Accelerometer; Adherence; Admission activity; Adolescent; Adolescent and Young Adult; Adolescent obesity; Adult; Aerobic; Age; Angiotensin Receptor; Angiotensin-Converting Enzyme Inhibitors; Arginine; Biological Markers; Brain natriuretic peptide; Cardiac; Cardiopulmonary; Cessation of life; Chemicals; Child; Child Health; Childhood; Chronic; Common Ventricle; Creatine; Data; Disease Progression; Dual-Energy X-Ray Absorptiometry; Echocardiography; Effectiveness; Endothelium; Equipment and supply inventories; Exercise; Exercise stress test; Goals; Health; Heart; Heart Transplantation; Heart failure; Intervention; Leg; Magnetic Resonance Imaging; Measures; Mission; Modality; Modeling; Morbidity - disease rate; Movement; Muscle Mitochondria; Muscle function; Nitrates; Nitric Oxide; Nitric Oxide Pathway; Nitrites; Obesity; Outcome; Patients; Physical Capacity; Physical Function; Physical activity; Physiologic pulse; Plasma; Population; Quality of life; Questionnaires; Randomized; Randomized Clinical Trials; Randomized Controlled Trials; Reproducibility; Research; Resistance; Risk; Scanning; Schools; Site; Supervision; Testing; Thinness; Translations; Transplant Recipients; Transportation; Treatment Failure; United States National Institutes of Health; VO2max; Work; Youth; adherence rate; arm; cardiorespiratory fitness; clinical application; congenital heart disorder; design; endothelial dysfunction; evidence base; exercise capacity; exercise intervention; exercise prescription; fitness; heart function; improved; improved outcome; indexing; mortality; multidisciplinary; muscle form; muscle strength; neonatal period; novel; novel strategies; novel therapeutic intervention; palliation; physical conditioning; prevent; primary outcome; reduced muscle mass; success; symposium; therapy design; treatment as usual

PROJECT SUMMARY Survival of children with single ventricles (“half a heart”) beyond the neonatal period has increased dramatically with the staged Fontan palliation. Yet, long-term morbidity remains high. By the age of 40, 50% of Fontan patients will have died or undergone heart transplantation. With >1,000 Fontan palliations performed in the US annually, there is a burgeoning population of Fontan patients at risk for progressive heart failure and death. Factors that contribute to onset and progression of heart failure in Fontan patients remain incompletely understood. However, it is established that Fontan patients have poor exercise capacity, associated with a greater risk of morbidity and mortality, in addition to decreased muscle mass, abnormal muscle function, and endothelial dysfunction contributing to disease progression. In adult patients with two ventricles and heart failure, reduced exercise capacity, muscle mass, and muscle strength are powerful predictors of poor outcomes, and exercise interventions can not only improve exercise capacity and muscle mass, but also reverse endothelial dysfunction. Limited exercise interventions in children with congenital heart disease have demonstrated that exercise is safe and effective; however, these studies have been conducted in small, heterogeneous groups, and most had few Fontan patients. Furthermore, none of these interventions have studied the impact of exercise on muscle mass or mitochondrial function, or endothelial function. We propose a milestone-driven, randomized controlled trial in pediatric Fontan patients to test the hypothesis that a live-video-supervised exercise (aerobic + resistance) intervention will improve cardiac and physical capacity; muscle mass, strength and function; and endothelial function. Adherence is a major limitation in pediatric exercise interventions delivered on-site, with adherence rates as low as 10%, due to distance from site, transportation difficulties, and missed school or work days. To overcome these challenges, we will utilize live-video conferencing to deliver the supervised exercise sessions. In our pilot exercise interventions, this approach resulted in excellent adherence (>85%) and improved exercise capacity and endothelial function. This proposal is designed to determine if the intervention improves: (Aim 1) cardiac and physical capacity (primary outcome: VO2 max), (Aim 2) muscle mass strength and function; and (Aim 3) endothelial function in pediatric Fontan patients. Our multidisciplinary team of experts will assess the effectiveness of a live-video-supervised exercise intervention, rigorously designed to maximize adherence and improve key and novel measures of health in pediatric Fontan patients associated with poor long-term outcomes. The use of exercise as a non-pharmacologic treatment modality in pediatric Fontan patients represents a paradigm shift, where standard therapies have failed. Our ultimate goal is the translation of this model to clinical application as an ”exercise prescription” to intervene early in pediatric Fontan patients and decrease long-term morbidity and mortality, in alignment with the NIH’s mission to develop evidence-based data for new approaches to improve outcomes in youth with chronic conditions.

项目概要 新生儿期后单心室（“半颗心”）儿童的存活率显着增加 与分阶段的 Fontan 姑息治疗。然而，长期发病率仍然很高。到 40 岁时，50% 的 Fontan 患者 将死亡或接受心脏移植。美国每年进行超过 1,000 例 Fontan 姑息治疗， 越来越多的 Fontan 患者面临进行性心力衰竭和死亡的风险。因素 导致 Fontan 患者心力衰竭发生和进展的因素尚不完全清楚。然而， 据证实，Fontan 患者的运动能力较差，与较高的发病风险和 死亡率，以及肌肉质量下降、肌肉功能异常和内皮功能障碍 有助于疾病进展。对于患有两个心室和心力衰竭的成年患者，减少运动 能力、肌肉质量和肌肉力量是不良结果的有力预测因素，而锻炼 干预措施不仅可以提高运动能力和肌肉质量，还可以逆转内皮功能障碍。 对先天性心脏病儿童进行有限的运动干预已证明运动是安全的 且有效；然而，这些研究是在小而异质的群体中进行的，而且大多数研究很少有 丰坦患者。此外，这些干预措施都没有研究运动对肌肉质量的影响 或线粒体功能，或内皮功能。我们提出了一个里程碑驱动的、随机控制的 在儿科 Fontan 患者中进行的试验，旨在检验以下假设：实时视频监督运动（有氧运动 + 阻力）干预将提高心脏和身体能力；肌肉质量、力量和功能； 和内皮功能。依从性是现场进行儿科运动干预的一个主要限制， 由于距离地点远、交通不便、缺课等原因，遵守率低至 10% 工作日。为了克服这些挑战，我们将利用实时视频会议来提供监督 锻炼课程。在我们的试点锻炼干预中，这种方法获得了出色的依从性 (>85%) 并改善运动能力和内皮功能。该提案旨在确定是否 干预改善：（目标 1）心脏和身体能力（主要结果：最大摄氧量），（目标 2）肌肉质量 力量和功能； （目标 3）Fontan 儿童患者的内皮功能。我们的多学科团队 专家将评估实时视频监督的锻炼干预措施的有效性，该干预措施经过严格设计，旨在 最大限度地提高依从性并改善与 Fontan 相关的儿科患者的关键和新颖的健康措施 长期结果不佳。使用运动作为小儿 Fontan 的非药物治疗方式 患者代表了一种范式转变，而标准疗法已经失败。我们的最终目标是翻译 该模型作为“运动处方”临床应用，对儿童 Fontan 患者进行早期干预 并降低长期发病率和死亡率，这符合 NIH 开发基于证据的使命 改善患有慢性病的青少年的结果的新方法的数据。