Skeletal Muscle Hypertrophy and Cardio-Metabolic Benefits After Spinal Cord Injury
Condition: Spinal Cord Injuries
MeSH terms: Spinal Cord Injuries; Hypertrophy; Wounds and Injuries
Study type: Interventional

Summary: 
      Spinal cord injury (SCI) is a devastating medical problem that affects thousands of civilian
      and military personnel in the United States. Spinal cord injuries (SCI) predispose
      individuals to impaired fitness, obesity, glucose intolerance and insulin resistance, placing
      them at greater risk for diabetes and coronary artery disease. These are devastating problems
      that occur frequently because of changes in body composition and reduced level of physical
      activity. Skeletal muscle wasting plays a central role in altered metabolism after SCI.
      Functional electrical stimulation (FES) is an effective rehabilitation tool that has been
      used to train the paralyzed skeletal muscles and which has shown some ability to ameliorate
      the deleterious effects of SCI on metabolism, particularly on insulin sensitivity. However,
      its ability to reverse skeletal muscle wasting is modest; most studies report limited gains
      in muscle mass and workload with highly variables outcomes from one study to another. This
      proposal was stimulated by the findings that a program of neuromuscular electrical
      stimulation resistance exercise prior to initiating functional electrical stimulation lower
      extremity cycling (FES-LEC) improves the gains in muscle mass and workload observed with FES.
      The specific objectives for the current proposal are to compare the impact of FES following
      evoking skeletal muscle hypertrophy of the lower extremity versus initiating FES cycling
      without introducing the hypertrophy effects on insulin sensitivity, control of blood sugar
      levels, oxygen uptake and amounts of muscle tissue and fat deposition. These studies could
      potentially have significant effects on thousands of people that will experience an SCI in
      the future as well as those living with SCI where prolonged paralysis is a major quality of
      life issue.

      There is a major need to investigate the mechanisms lead to maximize the benefits of FES
      applications and to understand cellular or molecular events that are associated with muscle
      hypertrophy and lead to promoting metabolic health after SCI. The designed study will provide
      a greater understanding regarding utilization of energy sources (like fats and sugars) in
      muscle
    

Detailed description: 
      Primary Objectives Aim #1: To determine the impact of 12+12 weeks of neuromuscular electrical
      stimulation (NMES)+FES-LEC on oxygen uptake, insulin sensitivity and glucose uptake in adults
      with SCI compared to control + FES-LEC.

      Aim #2: To determine the impact of 12+12 weeks of NMES+FES-LEC on skeletal muscle size,
      infiltration of intramuscular fat, visceral adiposity as well as fatigue resistance compared
      to control+ FES-LEC.

      . Aim #3 : To determine the impact of 12+12 weeks of NMES+FES-LEC on determinants of energy
      metabolism, protein molecules involved in insulin signaling, muscle hypertrophy and oxygen
      uptake (IRS-1, adenosine monophosphate kinase (AMPK), glucose transporter (GLUT-4), insulin
      like growth factor (IGF-1), Akt, mammalian target of rapamycin (mTOR) and Peroxisome
      proliferator-activated receptor coactivator (PGC-1 alpha) and electron transport chain
      proteins compared to control + FES-LEC only.

      Subjects: Forty eight chronic (1 year or more post-injury) individuals with motor complete
      SCI will be recruited from the Hunter Holmes McGuire VA Spinal Cord Dysfunction registry and
      Virginia Commonwealth University over 4 years.

      Inclusion Criteria

        1. All participants will be between 18-65 years old, men/women,

        2. greater than one year post SCI,

        3. Body mass index (BMI) < 30 Kg/m2.

        4. Participants must have C5-L2 level of injury, traumatic motor complete or incomplete SCI
           [American Spinal Injury Impairment Scale Classification (AIS A, B or C)].

      Exclusion Criteria:

        1. Participants with any of the following pre-existing medical conditions will be excluded
           (cardiovascular disease, uncontrolled type II diabetes mellitus, uncontrolled
           hypertension, and those on insulin, pressures sores stage 3 or greater), hematocrit
           above 50% or urinary tract infection or symptoms.

        2. Participants with osteoporosis (T-score equal or worse than -2.5 according to the World
           Health recommendation) will be excluded.

        3. Pregnant women and women who will be involved and become pregnant during the course of
           the study will be excluded as well.

      Study arms

        1. NMES+FES group (n =24; 2 days/week for 24 weeks); this group will undergo twice weekly
           of 12 weeks of surface NMES and ankle weights followed by 12 additional weeks of twice
           weekly of progressive FES-LEC using the RT300 bike. The total participation duration is
           24 weeks +3 weeks for measurements.

        2. Control + FES group (n =24; 2 days/week for 24 weeks); this group will undergo twice
           weekly of 12 weeks of passive leg extension/flexion with no ankle weights followed by 12
           additional weeks of twice weekly of progressive FES-LEC using the RT300 bike. The total
           participation duration is 24 weeks+3 weeks for measurements.
    

Intervention name(s): NMES+FES; Control+FES
Intervention type(s): Device; Device
Intervention description(s): 12 weeks of electrically evoked resistance training followed by 12 weeks of functional electrical stimulation cycling.; 12 weeks of passive movement followed by 12 weeks of functional electrical stimulation cycling.
Other intervention name(s): (NMES; Theratouch)+(FES; RTI300 Bike); Control+(FES; RTI300 Bike)
Allocation: Randomized
Intervention model: Parallel Assignment
Masking: None (Open Label)
Primary purpose: Health Services Research