Exercise For Sub-acute Stroke Patients in Jamaica

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.

Inclusion Criteria:

- Ischemic stroke within 8 weeks

- BMI of 18-40 kg/m2

- Able to walk 3 minutes with handrails, assistive device, or standby aid

Exclusion Criteria:

- 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