Novel Intervention to Influence Muscle Plasticity in Veterans
Condition: Spinal Cord Injuries
MeSH terms: Spinal Cord Injuries
Study type: Interventional

Summary: 
      The loss of muscle contraction (paralysis) removes an important stimulus for maintenance of
      overall health for individuals with complete spinal cord injury (SCI). Increased protein
      catabolism (atrophy) limits important stresses to the skeletal system. Bone loss doubles the
      risk of fracture and contributes to increased mortality in Veterans with SCI. Metabolic
      syndrome and diabetes lead to heart disease in Veterans with SCI at higher rates than the
      general population. Exercise methods to sustain muscle tissue, bone density, and metabolic
      stability after SCI are lacking scientific justification. If left unchecked, the secondary
      complications of SCI can be health limiting or even life threatening to Veterans with
      paralysis. The importance of maintaining the health of the musculoskeletal system after SCI
      has never been greater as a cure for paralysis may become a reality. Contemporary
      rehabilitation interventions lack the ability to functionally load muscle tissue, quantify
      the dose of load, stress the cardiovascular system, monitor the overall stresses during daily
      exercise training, or offer portability to improve compliance with the exercise. The
      long-term goal of this project is to establish the optimal dose of muscle and bone stress
      during functional exercise in order to improve the health of Veterans with complete
      paralysis. The practical outcome of this research is to offer a form of activity that is
      feasible, portable, and grounded in sound scientific principles. The scientific goal is to
      understand whether the dose of force generated in paralyzed muscle via evoked contractions is
      critical to muscle atrophy/hypertrophy molecular pathways, physiologic performance, and
      insulin sensitivity. The investigators will administer various doses of muscle force by
      manipulating the frequency of electrical stimulation while keeping stimulation current (i.e.
      muscle fiber recruitment) constant. Interestingly, no previous study has examined the dose of
      muscle force necessary to trigger adaptations in protein synthesis/degradation pathways. The
      investigators wish to discover the most effective method to maintain the molecular and
      physiologic properties of paralyzed muscle. The investigators believe such a method will be
      in urgent demand as a co-intervention with pharmaceutical strategies in post-SCI
      rehabilitation.
    

Detailed description: 
      Central Hypothesis: The investigators hypothesize that high muscle force induced via a novel,
      portable, active standing intervention will increase muscle force properties, alter gene
      expression for atrophy and fiber type pathways, and improve systemic insulin sensitivity in
      Veterans with complete paralysis.

      Aim 1: To determine the training effects of 3 tiers of quadriceps muscle force on muscle
      physiological properties in Veterans with chronic paralysis from SCI.

      Aim 2: To determine the training effects of 3 tiers of quadriceps muscle forces on muscle
      mRNA for genes associated with atrophy and muscle fiber type in Veterans with complete
      paralysis.

      Aim 3: To determine the training effects of 2 tiers of compressive load induced by quadriceps
      muscle forces on insulin sensitivity and markers of inflammation in Veterans with SCI.
    

Intervention name(s): Low-force muscle stimulation; High-force muscle stimulation; Sequential low-force and high-force muscle stimulation
Intervention type(s): Behavioral; Behavioral; Behavioral
Intervention description(s): Electrical stimulation of paralyzed muscle in seated or standing to evoke non-summated, low-force contractions, using either a lab-based system or a portable system for up to 1 year.; Electrical stimulation of paralyzed muscle in seated or standing to evoke summated, high-force contractions, using either a lab-based system or a portable system for up to 1 year.; Electrical stimulation of paralyzed muscle in seated or standing to evoke non-summated, low-force contractions, followed by: 1) a 1-month washout period, then; 2) electrical stimulation to evoke summated, high-force contractions.
Allocation: Non-Randomized
Intervention model: Single Group Assignment
Masking: None (Open Label)
Primary purpose: Treatment
Keywords: Quadriceps Muscle; RNA, Messenger; Hypertrophy; Electric Stimulation Therapy