Resistive Training Combined with Nutritional Therapy after Stroke

 描述(由申请人提供)： 背景：我们的退伍军人事务部研究团队在记录中风致残后伴随慢性偏瘫的显著骨骼肌萎缩方面发挥了重要作用。与非瘫痪腿相比，瘫痪腿的肌肉体积减少了24%，这对力量、功能、健康、新陈代谢和一般健康都有重大影响。我们以前的工作建立了渐进式高强度阻力训练(RT)作为老年卒中幸存者的有效康复策略，在偏瘫和非偏瘫侧都产生了大腿肌肉肥大。在健康人群中，补充蛋白质可以显著增加放疗后肌肉质量的增加，但尚未在中风中进行实验。来自我们小组的新的初步数据表明，中风患者摄入的蛋白质比老年人推荐的每日摄入量(0.80克/公斤/天)少20%，这表明在蛋白质摄入充足的情况下，骨骼肌的相对增长可能会显着更好。新的数据还表明，腿部肌肉质量可以预测中风患者的静息代谢率(RMR)，这意味着旨在最大化肌肉收益的营养和RT联合治疗将转化为改善能量平衡，这是康复成功的关键因素。更好地理解积极的RT干预的真正潜力，以解决中风相关的萎缩和相关问题，以最大限度地受益，有待于临床试验直接比较RT加和不加营养治疗。目的：我们计划首次进行为期12周的随机安慰剂对照临床试验，比较补充1.2g/kg蛋白质(RT+PRO)和RT+等热量安慰剂(RT+PLA)对慢性卒中患者的身体成分、肥厚调节、力量、肌肉质量、功能活动度和能量消耗的影响。目的1：比较12周RT+PRO和RT+PLA对DXA测定的全身瘦组织质量和CT测定的股部肌肉体积的影响。目的2：评估卒中存活者RT+PRO与RT+PLA中骨骼肌质量关键调节因子(myostatin、mTOR及其下游信号网络)的变化。目的：采用5日加速度法测定RT+PRO和RT+PLA对小腿力量、单位肌肉体积力量(肌肉质量，MQ)、功能活动度(6min步行距离、10m步行时间)、RMR和自由生活体力活动的影响。方法：将88例年龄40~85岁、体重指数20~40 kg/m2的偏瘫缺血性卒中患者随机分为两组，每周3次，分别给予等量补充热量的RT+PRO或RT+PLA。受试者将在接受RT+PRO或RT+PLA3个月前后接受力量和体能测试、身体成分扫描、双侧骨骼肌活组织检查、功能结果测试和能量消耗评估。影响：拟议的Merit研究对遭受中风相关肌肉萎缩后果的退伍军人具有临床和实际意义。尽管健康人群在运动后摄入膳食蛋白质后表现出肌肉蛋白质合成的增强和分解的抑制，但尚未有关于中风的研究。这一优点直接解决了这一差距，通过引入第一条营养建议与锻炼相结合来改善肌肉和代谢健康，从而改变国际最佳实践，从而减少残疾并战胜中风老兵幸存者的石棺减少症。

 DESCRIPTION (provided by applicant): Background: Our VA research team has played a prominent role in documenting the significant skeletal muscle atrophy that accompanies chronic hemiparesis after disabling stroke. Muscle volume is reduced by 24% in paretic vs. non-paretic legs, having significant implications for strength, function, fitness, metabolism and general health. Our previous work establishes progressive, high-intensity resistive training (RT) as an effective rehabilitation strategy for oldr stroke survivors, producing thigh muscle hypertrophy on both the paretic and non-paretic sides. Protein supplementation can significantly augment gains in muscle mass after RT in healthy populations, but no experiments have yet been conducted in stroke. New preliminary data from our group indicates that stroke participants consume 20% less protein than the recommended daily amount for older individuals (0.80 vs. 1.0 g/kg/day) suggesting that relative gains in skeletal muscle could be significantly better in the presence of adequate protein intake. New data also indicates that leg muscle mass predicts resting metabolic rate (RMR) in stroke, implying that a combined nutrition and RT therapy aimed at maximizing muscle gains would translate into improved energy balance, a key factor in rehabilitation success. A better understanding of the true potential for aggressive RT interventions to address stroke-related atrophy and related problems for maximum benefit awaits clinical trials directly comparing RT with and without nutritional therapy. Objectives: We propose to be the first to conduct a 12-week randomized placebo controlled clinical trial comparing the effects of RT+ protein supplementation at 1.2 g/kg/day (RT+PRO) vs. RT+isocaloric placebo (RT+PLA) on body composition, hypertrophy regulation, strength, muscle quality, functional mobility and energy expenditure in chronic stroke. Aim 1: Compare effects of 12 weeks RT+PRO and RT+PLA on whole body lean tissue mass by DXA and thigh region muscle volume by CT. Aim 2: Assess changes to key regulators of skeletal muscle mass (myostatin, mTOR and their downstream signaling network) in RT+PRO vs. RT+PLA in stroke survivors. Aim 3: Determine the effects of RT+PRO and RT+PLA on leg strength, strength per unit muscle volume (muscle quality, MQ), functional mobility (6-minute walk distance, 10-meter walk time), RMR and free-living physical activity by 5-day accelerometry. Methods: To accomplish aims, 88 hemiparetic ischemic stroke subjects aged 40-85 years, BMI 20-40 kg/m2 will be randomized to either 3x/week RT+PRO or RT +PLA (equal calories for supplements) with nutritional counseling in both groups. Subjects will undergo strength and fitness tests, body composition scans, bilateral skeletal muscle biopsies, functional outcomes tests and energy expenditure assessments before and after 3 months of RT+PRO or RT+PLA. Impact: The proposed Merit study has clinical and practical implications for Veterans suffering from the consequences of stroke-related muscle wasting. Although healthy populations show enhanced muscle protein synthesis and inhibited breakdown following post exercise dietary protein intake, no work has yet been conducted in stroke. This Merit directly addresses this gap to change international best practice by introducing the 1st nutritional recommendations in combination with exercise to improve muscle and metabolic health that will reduce disability and defeat sarcopenia for Veteran stroke survivors.