Resistive Training Combined with Nutritional Therapy after Stroke

 描述（由申请人提供）： 背景资料：我们的VA研究团队在记录致残性中风后伴随慢性轻偏瘫的显著骨骼肌萎缩方面发挥了突出作用。肌肉体积减少了24%，在轻瘫与非轻瘫腿，具有显着的影响力量，功能，健身，新陈代谢和一般健康。我们以前的工作建立了渐进式高强度抗阻训练（RT）作为老年中风幸存者的有效康复策略，使瘫痪和非瘫痪侧的大腿肌肉肥大。补充蛋白质可以显著增加健康人群RT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，中风参与者消耗的蛋白质比老年人推荐的每日量少20%（0.80与1.0 g/kg/天），这表明在足够的蛋白质摄入的情况下，骨骼肌的相对增益可能会显着更好。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），这意味着旨在最大限度地增加肌肉的营养和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。更好地了解积极的RT干预的真正潜力，以解决中风相关的萎缩和相关问题的最大利益，等待临床试验直接比较RT与营养治疗。目的：我们计划首先进行一项为期12周的随机安慰剂对照临床试验，比较RT+蛋白质补充剂（1.2 g/kg/d）（RT+PRO）与RT+等热量安慰剂（RT+PLA）对慢性卒中患者的身体成分、肥大调节、力量、肌肉质量、功能活动性和能量消耗的影响。目的1：比较12周RT+PRO和RT+PLA对DXA测量的全身瘦组织质量和CT测量的大腿区域肌肉体积的影响。目标二：评估卒中幸存者中RT+PRO与RT+PLA中骨骼肌质量关键调节因子（肌生长抑制素、mTOR及其下游信号网络）的变化。目标3：通过5天加速度计测定RT+PRO和RT+PLA对腿部力量、单位肌肉体积力量（肌肉质量，MQ）、功能移动性（6分钟步行距离、10米步行时间）、RMR和自由生活体力活动的影响。研究方法：为实现目标，88例年龄在40-85岁、BMI 20-40 kg/m2的轻偏瘫缺血性卒中受试者将随机接受每周3次RT+PRO或RT +PLA（补充剂的热量相等），两组均接受营养咨询。受试者将在RT+PRO或RT+PLA治疗前和治疗后3个月接受力量和体能测试、身体成分扫描、双侧骨骼肌活检、功能结局测试和能量消耗评估。影响：拟议的Merit研究对患有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显示出增强的肌肉蛋白质合成和抑制的分解，但尚未在中风中进行研究。这一优点直接解决了这一差距，通过引入第一营养建议与运动相结合来改变国际最佳实践，以改善肌肉和代谢健康，从而减少残疾并击败退伍军人中风幸存者的肌肉减少症。

 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.