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

基本信息

批准号：
10378166
负责人：
Daniel Bernstein
金额：
$ 70.8万
依托单位：
STANFORD UNIVERSITY
依托单位国家：
美国
项目类别：
财政年份：
2020
资助国家：
美国
起止时间：
2020-03-10 至 2025-02-28
项目状态：
未结题

来源：
https://reporter.nih.gov/project-details/10378166
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 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 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 Videoconferencing Work Youth adherence rate arm cardiorespiratory fitness clinical application congenital heart disorder design effectiveness evaluation 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 obese person palliation physical conditioning prevent primary outcome reduced muscle mass success therapy design treatment as usual

项目摘要

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然而，到 40 岁时，50% 的 Fontan 患者的长期发病率仍然很高。将死亡或接受心脏移植在美国每年进行超过 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。然而，对于 Fontan 患者心力衰竭的发生和进展的影响尚不完全清楚。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在患有两个心室和心力衰竭的成年患者中，减少运动会导致疾病进展。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，这些研究是在小规模、异质群体中进行的，而且大多数研究的结果很少此外，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）干预将改善心脏和身体的肌肉质量、力量和功能；和内皮功能是现场进行儿科运动干预的主要限制。由于距离地点较远、交通不便、缺课或缺课等原因，遵守率低至 10% 为了克服这些挑战，我们将利用实时视频会议来提供监督。在我们的试点锻炼干预中，这种方法获得了良好的依从性（>85%）。并改善运动能力和内皮功能。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；以及（目标 3）儿童 Fontan 患者的内皮功能。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使用运动作为儿童 Fontan 的非药物治疗方式的长期效果不佳。患者代表了一种范式转变，而我们的最终目标是转化。将该模型作为“运动处方”应用于临床，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。