Strength Training for Skeletal Muscle Adaptation After Stroke
Condition: Stroke
MeSH terms: Stroke
Study type: Interventional

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 the investigators' 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.
    

Detailed 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. The investigators 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 the investigators will
      screen and consent chronic stroke patients with residual gait deficits. Phase 2 (3 weeks)
      will consist of baseline testing that includes dual energy X-ray absorptiometry (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.
    

Intervention name(s): Exercise- Strength Training; Exercise- Stretching Control
Intervention type(s): Other; Other
Intervention description(s): 3x per week lower-extremity ST lasting approximately 45 minutes to 1 hour.; 3x per week upper and lower body stretching mixed with active and passive range of motion exercises
Allocation: Randomized
Intervention model: Parallel Assignment
Masking: None (Open Label)
Primary purpose: Treatment
Keywords: Stroke; Exercise; Strength Training; Skeletal Muscle; Insulin Sensitivity