Exercise For Sub-acute Stroke Patients in Jamaica

Stroke Clinical Trial

— JAMMS  

Official title:

Jamaica and Maryland Mobility in Stroke

Clinical Trial Details — Status: Recruiting

Administrative data

• NCT number: NCT01392391
• Other study ID #: HP-00048469
• Secondary ID: R01HD068712
• Status: Recruiting
• Phase: Phase 2
• First received: July 11, 2011
• Last updated: October 28, 2016
• Start date: July 2011
• Est. completion date: April 2018

Study information

• Verified date: October 2016
• Source: Baltimore VA Medical Center
• Contact: Richard F Macko, MD
• Phone: 410-605-7063
• Email: rmacko[@]grecc.umaryland.edu
• Is FDA regulated: No
• Health authority: United States: Federal GovernmentJamaica: Ministry of Health
• Study type: Interventional

Clinical Trial 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.

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.

Recruitment information / eligibility

• Status: Recruiting
• Enrollment: 150
• Est. completion date: April 2018
• Est. primary completion date: April 2018
• Accepts healthy volunteers: No
• Gender: Both
• Age group: 18 Years to 85 Years

Eligibility

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

Study Design

Allocation: Randomized, Endpoint Classification: Safety/Efficacy Study, Intervention Model: Parallel Assignment, Masking: Open Label, Primary Purpose: Treatment

Related Conditions & MeSH terms

• Stroke

Intervention

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"
• 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

Locations

Country	Name	City	State
Jamaica	University of West Indies	Kingston	Mona 7
United States	University of Maryland	Baltimore	Maryland

Sponsors (2)

Lead Sponsor	Collaborator
Baltimore VA Medical Center	Eunice Kennedy Shriver National Institute of Child Health and Human Development (NICHD)

Countries where clinical trial is conducted

United States,  Jamaica, 

References & Publications (3)

Lam JM, Globas C, Cerny J, Hertler B, Uludag K, Forrester LW, Macko RF, Hanley DF, Becker C, Luft AR. Predictors of response to treadmill exercise in stroke survivors. Neurorehabil Neural Repair. 2010 Jul-Aug;24(6):567-74. doi: 10.1177/1545968310364059. Epub 2010 May 7. — View Citation

Luft AR, Macko RF, Forrester LW, Villagra F, Ivey F, Sorkin JD, Whitall J, McCombe-Waller S, Katzel L, Goldberg AP, Hanley DF. Treadmill exercise activates subcortical neural networks and improves walking after stroke: a randomized controlled trial. Stroke. 2008 Dec;39(12):3341-50. doi: 10.1161/STROKEAHA.108.527531. Epub 2008 Aug 28. — View Citation

Michael K, Goldberg AP, Treuth MS, Beans J, Normandt P, Macko RF. Progressive adaptive physical activity in stroke improves balance, gait, and fitness: preliminary results. Top Stroke Rehabil. 2009 Mar-Apr;16(2):133-9. doi: 10.1310/tsr1602-133. — View Citation

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Thigh and Abdominal muscle and fat	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.	Baseline and 6 months	No
Primary	Whole body protein and skeletal muscle synthesis and breakdown	Serial blood sampling and pre-/post-muscle biopsies in the fasted and fed state	Baseline and 6 months	No
Primary	Muscle myosin heavy chain isoform (MHC) proportions	Analysis of muscle biopsies for MHC fiber type proportions	Baseline and 6 months	No
Primary	Leg Strength	1 repetitive maximum strength for leg extension, quadriceps and hamstring muscles	Baseline and 6 months	No
Primary	Fitness	VO2 peak testing with open circuit spirometry	Baseline and 6 months	No
Primary	Glucose tolerance	2 hour oral glucose tolerance test with serial blood sampling every 30 minutes for glucose and insulin	Baseline and 6 months	No
Secondary	Muscle TNF alpha	Analysis of muscle biopsy samples for TNF levels	Baseline and 6 months	No
Secondary	Mobility and balance	Stroke deficit profile will be indexed by NIH Stroke Scale, modified Ashworth, timed walks, Short Physical Performance Battery, Berg Balance.	Baseline and 6 months	No

External Links

•   American Stroke Association
•   University of West Indies Tropical Medicine Research Unit
•   Veterans Affairs Maryland Exercise and Robotics Center of Excellence