JAMMS: Exercise For Sub-acute Stroke Patients in Jamaica

Sponsor

Baltimore VA Medical Center (U.S. Fed)

Overall Status

Unknown status

CT.gov ID

NCT01392391

Collaborator

Eunice Kennedy Shriver National Institute of Child Health and Human Development (NICHD) (NIH)

150

Enrollment

Locations

Arms

Duration (Months)

Patients Per Site

0.9

Patients Per Site Per Month

Study Details

Study Description

Brief Summary

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.

Condition or Disease	Intervention/Treatment	Phase
Stroke	Procedure: Task Oriented Exercise Training Procedure: Stroke Care "Get with the Guidelines"	Phase 2

Detailed Description

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.

Study Design

Study Type:

Interventional

Anticipated Enrollment :

150 participants

Allocation:

Randomized

Intervention Model:

Parallel Assignment

Masking:

None (Open Label)

Primary Purpose:

Treatment

Official Title:

Jamaica and Maryland Mobility in Stroke

Study Start Date :

Jul 1, 2011

Anticipated Primary Completion Date :

Apr 1, 2018

Anticipated Study Completion Date :

Apr 1, 2018

Arms and Interventions

Arm	Intervention/Treatment
Experimental: Exercise Task-oriented exercise training (aerobic, strength, and balance exercises)	Procedure: Task Oriented Exercise Training Treadmill training with safety harnesses begin at 6 to 15 minutes total duration at 40-50% maximal heart rate reserve 3 times per week, increasing to 60-70% maximal heart rate reserve for 30 minutes for 6 months. Group dynamic balance exercise immediately follow the treadmill training 3 times a week. Participants also receive Best Stroke Care according to "Get with the Guidelines"
Active Comparator: Stroke Care Best Medical Care in Jamaica adapted from the American Stroke Association "Get with the Guidelines".	Procedure: Stroke Care "Get with the Guidelines" Post-stroke care is applied according to the recommendations of the American Stroke Association "Get with the Guidelines" adapted for Jamaica

Arm

Intervention/Treatment

Experimental: Exercise

Task-oriented exercise training (aerobic, strength, and balance exercises)

Procedure: Task Oriented Exercise Training

Treadmill training with safety harnesses begin at 6 to 15 minutes total duration at 40-50% maximal heart rate reserve 3 times per week, increasing to 60-70% maximal heart rate reserve for 30 minutes for 6 months. Group dynamic balance exercise immediately follow the treadmill training 3 times a week. Participants also receive Best Stroke Care according to "Get with the Guidelines"

Active Comparator: Stroke Care

Best Medical Care in Jamaica adapted from the American Stroke Association "Get with the Guidelines".

Procedure: Stroke Care "Get with the Guidelines"

Post-stroke care is applied according to the recommendations of the American Stroke Association "Get with the Guidelines" adapted for Jamaica

Outcome Measures

Primary Outcome Measures

Thigh and Abdominal muscle and fat [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 [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 [Baseline and 6 months]
Analysis of muscle biopsies for MHC fiber type proportions
Leg Strength [Baseline and 6 months]
1 repetitive maximum strength for leg extension, quadriceps and hamstring muscles
Fitness [Baseline and 6 months]
VO2 peak testing with open circuit spirometry
Glucose tolerance [Baseline and 6 months]
2 hour oral glucose tolerance test with serial blood sampling every 30 minutes for glucose and insulin

Secondary Outcome Measures

Muscle TNF alpha [Baseline and 6 months]
Analysis of muscle biopsy samples for TNF levels
Mobility and balance [Baseline and 6 months]
Stroke deficit profile will be indexed by NIH Stroke Scale, modified Ashworth, timed walks, Short Physical Performance Battery, Berg Balance.

Eligibility Criteria

Criteria

Ages Eligible for Study:

18 Years to 85 Years

Sexes Eligible for Study:

All

Accepts Healthy Volunteers:

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,

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),

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