Exercise For Sub-acute Stroke Patients in Jamaica (JAMMS)

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.

Phase 1 consists of recruitment and screening of individuals with mild to moderate hemiparetic stroke from UWI Accident and Emergency Room and Neurology Stroke Clinics. Phase 2: Subjects with hemiparetic gait ≤ 8 weeks post-stroke who are not wheelchair bound or bed are approached for informed consent, medical, neurologic, blood tests, and treadmill (TM) exercise tests to determine study eligibility. Phase 3 baseline testing includes measures of fitness, oral glucose tolerance test (OGTT), body composition, bilateral vastus lateralis muscle biopsies, stable isotope measures of protein synthesis and breakdown. Phase 4: Eligible subjects are randomized to 6 months 3x/week TEXT or control group with best medical care alone that includes American Stroke Association (ASA) physical activity guideline recommendations for walking 4x/week. Randomization is stratified based on glucose tolerance (normal vs. abnormal) and gait deficit severity. Subjects have limited 3 month testing of fitness levels (VO2 peak), body composition, fasting glucose and insulin levels to document the natural history (controls) and temporal profile of exercise-mediated adaptations (TEXT) as they transition from the sub-acute into chronic phase of stroke. Phase 5 is 6-month post-intervention testing.