Jamaica and Maryland Mobility in Stroke
试验速览
- 阶段
- 2 期
- 入组人数
- 150
- 试验地点
- 3
- 主要终点
- Thigh and Abdominal muscle and fat
研究概览
简要总结
Chronic hemiparetic stroke is associated changes in body composition, skeletal muscle and cardiometabolic health; specific changes include paretic limb muscular atrophy, increased intramuscular fat deposition, elevated prevalence of impaired glucose tolerance and type 2 diabetes. This randomized intervention study compares a 6 month task oriented exercise programs versus control with both groups receiving best medical stroke care according to American Stroke Association "Get with the Guidelines". The hypothesis is that is 6 months of task-oriented exercise initiated early across the sub-acute period of stroke can prevent or ameliorate the natural course of these body composition, skeletal muscle and cardiometabolic health changes.
详细描述
Stroke leads to profound cardiovascular deconditioning and secondary abnormalities in paretic skeletal muscle that worsen cardiovascular health. Conventional rehabilitation focuses on restoration of daily function, without an adequate exercise stimulus to address deconditioning or the muscle abnormalities that may propagate insulin resistance (IR) to worsen risk for type 2 diabetes mellitus (T2DM) and recurrent stroke. By the time individuals reach chronic stroke (>6 months), we report hemiparetic body composition abnormalities including paretic leg muscular atrophy, increased intramuscular area fat, and a major shift to fast myosin heavy chain (MHC). All of these factors promote IR, which has been linked to reduced muscle protein synthesis in aging that may be reversible with exercise. We also find elevated tumor necrosis factor alpha (TNFα) in paretic leg muscle, suggesting that inflammation may affect protein synthesis and breakdown, similar to sarcopenia in aging. Yet, no prior studies have considered stroke as a catabolic syndrome modifiable by early exercise to improve muscle and cardiometabolic health.
Aim #1. Paretic (P) and non-paretic (NP) leg mixed muscle protein synthesis and breakdown in the fed and fasted state, TNFα expression, thigh muscle volume and strength.
Hypothesis 1: Paretic leg has reduced muscle protein synthesis and increased breakdown compared to non-paretic leg; TEXT will increase mixed muscle protein synthesis and reduce breakdown to increase muscle volume and strength by the mechanism(s) of reducing inflammation in the paretic leg, compared to controls.
Aim # 2. Glucose tolerance, fitness, and muscle phenotype. Hypothesis 2: TEXT will improve fitness levels, insulin and glucose response to oral glucose challenge, and increase paretic leg slow twitch (slow MHC) muscle molecular phenotype.
This randomized study investigates the hypothesis that in African-Jamaican adults with recent hemiparetic stroke, 6 months of TEXT across the sub-acute and into the chronic phase of stroke will improve paretic leg muscle and cardiometabolic health, compared to controls receiving best medical care.
研究设计
- 研究类型
- Interventional
- 分配方式
- Randomized
- 干预模型
- Parallel
- 主要目的
- Treatment
- 盲法
- None
入排标准
- 年龄范围
- 18 Years 至 85 Years（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •Ischemic stroke within 8 weeks
- •BMI of 18-40 kg/m2
- •Able to walk 3 minutes with handrails, assistive device, or standby aid
排除标准
- •Actively exercising for >30 minutes per day for 5 days per week
- •Increased alcohol consumption (> 2 oz. liquor, 8 oz. wine, 24 oz. beer per day)
- •Active abuse of other illegal and illicit drugs
- •Cardiac History of: a) unstable angina, b) recent (<3 months) myocardial infarction, congestive heart failure (NYHA category II-IV), c) hemodynamically significant valvular dysfunction
- •Medical History: a) peripheral arterial disease with vascular claudication making exercise challenging, b) orthopedic or chronic pain condition(s) restricting exercise, c) pulmonary or renal failure, d) active cancer, e) untreated poorly controlled hypertension measured on at least 2 occasions (greater than 160/100), f) HIV-AIDS or other known inflammatory responses, g) sickle cell anemia, h) medications: heparin, warfarin, lovenox, or oral steroids, j) currently pregnant
- •Endocrine History: a) type 1 diabetes or insulin dependent type 2 diabetes, b) poorly controlled type 2 diabetes (HbA1C > 10)
- •Neurological History: a) dementia (Mini-Mental Status score < 23 or < 17 if education level at or below 8th grade) and clinical confirmation by clinical evaluation, b) severe receptive or global aphasia that confounds testing and/or training, operationally defined as unable to follow 2 point commands, c) hemiparetic gait from a prior stroke preceding the index stroke defining eligibility (more than one stroke), d) neurologic disorder restricting exercise such as Parkinsons or myopathy, e) untreated major depression (CESD > 16 or clinical confirmation), f) muscular disorder (s) restricting exercise
- •Muscle biopsy exclusion criteria: a) anti-coagulation therapy with heparin, warfarin, or lovenox (anit-platelet therapy is permitted), b)bleeding disorder
结局指标
主要结局
Thigh and Abdominal muscle and fat
时间窗: Baseline and 6 months
CT scans to determine 1) mid-thigh cross sectional area for muscle area, intramuscular and subcutaneous fat area, and quality of lean tissue mass, 2) abdominal fat area.
Whole body protein and skeletal muscle synthesis and breakdown
时间窗: Baseline and 6 months
Serial blood sampling and pre-/post-muscle biopsies in the fasted and fed state
Muscle myosin heavy chain isoform (MHC) proportions
时间窗: Baseline and 6 months
Analysis of muscle biopsies for MHC fiber type proportions
Leg Strength
时间窗: Baseline and 6 months
1 repetitive maximum strength for leg extension, quadriceps and hamstring muscles
Fitness
时间窗: Baseline and 6 months
VO2 peak testing with open circuit spirometry
Glucose tolerance
时间窗: Baseline and 6 months
2 hour oral glucose tolerance test with serial blood sampling every 30 minutes for glucose and insulin
次要结局
- Muscle TNF alpha(Baseline and 6 months)
- Mobility and balance(Baseline and 6 months)
研究者
Rich Macko
MD
Baltimore VA Medical Center