Overview

This trial is active, not recruiting.

Condition stroke
Treatments exercise- strength training, exercise- stretching control
Sponsor Department of Veterans Affairs
Start date April 2009
End date August 2013
Trial size 60 participants
Trial identifier NCT00827827, B6737-R, H30631

Summary

Chronically disabled stroke survivors experience accelerated skeletal muscle atrophy and other detrimental changes to muscle and surrounding tissues on the paretic side. This unilateral tissue-level damage contributes to worsening disability and insulin resistance. This VA Merit Award will advance our understanding of the potential for strength training (ST) to reverse stroke-related muscle abnormalities to improve metabolic health, strength, and function. It will be the first study to thoroughly investigate the effects of ST on muscle atrophy, intramuscular fat, muscle fiber characteristics, capillary density and insulin sensitivity after stroke.

United States No locations recruiting
Other Countries No locations recruiting

Study Design

Allocation randomized
Endpoint classification efficacy study
Intervention model parallel assignment
Masking open label
Primary purpose treatment
Arm
(Experimental)
Participants in this group undergo lower-extremity strength training on three pneumatic resistance machines (Keiser Leg Press, Keiser Leg Extension, and Keiser Leg Curl). Training sessions happen 3 times per week (M,W,F) and last approximately 45 minutes to 1 hour. Participants in this group exercise each limb individually to account for the large discrepancies in strength between legs in stroke survivors.
exercise- strength training
3x per week lower-extremity ST lasting approximately 45 minutes to 1 hour.
(Active Comparator)
Participants in this group receive equal exposure to study staff compared with the experimental ST group (approximately 45 minutes to 1 hour 3 times per week). Exercise sessions for this group involve a full battery of active and passive...upper and lower body...stretching and range of motion exercises performed on raised padded tables.
exercise- stretching control
3x per week upper and lower body stretching mixed with active and passive range of motion exercises

Primary Outcomes

Measure
Bilateral Thigh Intramuscular Fat by CT
time frame: baseline and 3 months
Bilateral Thigh Muscle Area and Volume by CT scan
time frame: baseline and 3 months (post intervention)
Balance Testing using Berg Balance Scale
time frame: baseline and 3 months
Peak Fitness by graded treadmill VO2 peak testing
time frame: baseline and 3 months
Bilateral Single Limb Muscle Endurance (Static and Dynamic)
time frame: baseline and 3 months

Secondary Outcomes

Measure
Histochemical analyses of fiber type and capillary density from Bilateral Thigh Muscle Biopsy samples
time frame: baseline and 3 months
Muscle Fiber proportion and mean cross sectional area by immunohistochemistry
time frame: baseline and 3 months
Myosin Heavy Chain Isoform expression by gel electrophoresis
time frame: baseline and 3 months
Skeletal Muscle TNF-alpha transcript expression by RT-PCR
time frame: baseline and 3 months
Muscle Inflammatory Infiltrates by Immunohistochemistry
time frame: baseline and 3 months
Oral Glucose tolerance Test
time frame: baseline and 3 months
Insulin Sensitivity by Hyperglycemic Clamp Test
time frame: baseline and 3 months
Bilateral Single Limb Strength Testing (Leg Extension and Leg Press)
time frame: baseline and 3 months
Timed Walks (10 meter and 6 minute walk tests
time frame: baseline and 3 months
Cognitive Function
time frame: baseline and 3 months

Eligibility Criteria

Male or female participants from 40 years up to 85 years old.

Inclusion Criteria: - Stroke greater than 6 months prior with residual hemiparetic gait in women or men aged 40-85 years - Completion of all regular post-stroke physical therapy - Adequate language and neurocognitive function to participate in testing and training and to give adequate informed consent Exclusion Criteria: - Alcohol consumption greater than 3 oz. liquor, or 3 x 4 oz glasses of wine, or 3 x 12 oz. beers per day, by self-report - clinical history of - unstable angina - recent (less than 3 months) myocardial infarction or congestive heart failure (NYHA category II) - hemodynamically significant valvular dysfunction - PAOD with claudication - major orthopedic, chronic pain, or non-stroke neuromuscular disorders restricting exercise - pulmonary or renal failure - poorly controlled hypertension (greater than 190/110) - recent hospitalization for severe disease or surgery - severe or global receptive aphasia which confounds reliable testing and training - Allergy to lidocaine - Known muscle disorder - Taking Coumadin or Lovenox (contraindication for muscle biopsies) - Dementia - Untreated major depression.

Additional Information

Official title Strength Training for Skeletal Muscle Adaptation After Stroke
Principal investigator Fred M Ivey, PhD
Description This study investigates the hypothesis that a novel, high intensity, high repetition ST program will improve abnormalities in paretic and non-paretic leg muscle volume and composition compared to an attention-matched control regimen of supervised stretching over a 3-month intervention period in those disabled by stroke. We further hypothesize that ST-induced skeletal muscle adaptation will translate into improved insulin sensitivity, strength, and function in this population. The specific objectives are to: 1) Determine the effects ST compared to a control intervention on paretic and non-paretic abnormalities in skeletal muscle volume, intramuscular fat, muscle fiber distribution, muscle capillary density, and muscle inflammation in chronically disabled stroke survivors. 2) Determine the effects ST compared to a control intervention on insulin sensitivity in stroke survivors, and whether structural and cellular skeletal muscle mechanisms contribute to improvements in insulin sensitivity after ST. 3) Determine the effects ST compared to a control intervention on physical function (strength, walking speed and balance) in stroke survivors, and whether structural skeletal muscle mechanisms predict ST-induced functional improvement. The project design consists of 4 phases over 5 months for stroke participants enrolled in either of the two intervention arms (ST vs. CONTROL). During phase 1 we will screen and consent chronic stroke patients with residual gait deficits. Phase 2 (3 weeks) will consist of baseline testing that includes DEXA scanning, bilateral CT scanning of the legs, bilateral vastus lateralis muscle biopsies, strength testing, timed walks, balance measurements, oral glucose tolerance testing, and hyperglycemic clamp testing. Following completion of baseline testing, volunteers are to be randomized to ST or the CONTROL group. Phase 3 (Intervention Phase, 3 months) will begin with 2 sessions of acclimatization for those assigned to the ST group. ST will then be progressed to 2 sets of 20 repetitions on each leg on each machine (Keiser Leg Press, Leg Extension, Leg Curl) with gradual increases in resistance over 3 months. Those in the CONTROL group will receive equal exposure to health care personnel in the Baltimore VA Exercise facility, performing a full battery of upper and lower body passive and active stretching exercises at each intervention session. In Phase 4 all baseline testing and laboratory analyses will be repeated. Developing evidence-based therapies to combat skeletal muscle deterioration is highly relevant for chronically disabled stoke survivors. There is mounting evidence that current models of post-stroke rehabilitation are not optimal for maximizing recovery of muscle mass, strength, and metabolic health. The proposed research will develop new insight into the utility of progressive ST for reversing detrimental changes to gross muscle composition, muscle molecular phenotype, muscle inflammation, and muscle capillarization. Changes to any or all of these muscle parameters should have measurable impact on both whole body insulin sensitivity and function. Collectively, the results from this trial may change the current standard of care for stroke survivors by providing evidenced reasons for augmenting physical therapists' treatments, allowing more intense and diverse therapy sessions for maintenance of skeletal muscle.
Trial information was received from ClinicalTrials.gov and was last updated in October 2014.
Information provided to ClinicalTrials.gov by Department of Veterans Affairs.