Resistance Training and Testosterone After Spinal Cord Injury
Condition: Spinal Cord Injury
MeSH terms: Spinal Cord Injuries; Wounds and Injuries
Study type: Interventional
Phase: Phase 2/Phase 3

Summary: 
      The goal of this proposal is to investigate the efficacy of a complimentary approach of
      evoked resistance training and testosterone replacement therapy on the changes in body
      composition and metabolic profile after SCI. The proposed method could become a recommended
      and simple intervention especially for individuals with limited access and poor tolerance to
      exercise. The rationale is based on the evidence that individuals with SCI experience decline
      in anabolic hormones which may be responsible for the deterioration in body composition and
      metabolic profiles and leads to increase obesity, type 2 diabetes mellitus, dyslipidemia and
      subsequently cardiovascular disease. The designed study will provide explanation to the
      adaptations in the energy source of the muscle cells in response to training.
    

Detailed description: 
      Individuals with spinal cord injury (SCI) are at a lifelong risk of increasing obesity and
      several chronic metabolic disorders such as glucose intolerance, insulin resistance and
      dyslipidemia secondary to deterioration in body composition. Within few weeks of injury,
      there are significant decrease in whole body fat-free mass (FFM), particularly lower
      extremity skeletal muscle mass and subsequent increase in fat mass (FM). Resistance training
      (RT) is an important type of exercise that has been shown to induce positive physiological
      adaptations such as increasing lean mass and reducing metabolic disorders in other clinical
      populations.

      In a pilot work, the investigators provided evidence that evoked RT using surface
      neuromuscular electrical stimulation (NMES) for knee extensor muscle group resulted in
      significant increase skeletal muscle cross-sectional area (CSA), reduction in % leg FM and a
      trend towards decrease in visceral adipose tissue (VAT) CSA. The favorable adaptations in
      body composition were associated with decrease in plasma insulin area under the curve and
      plasma triglycerides. The investigators attributed the adaptations in body composition and
      metabolic profile to an associated increase in plasma insulin-like growth factor (IGF-1). The
      investigators concluded that twelve weeks of evoked RT targeted towards evoking skeletal
      muscle hypertrophy could result in significant body composition and metabolic adaptations in
      individuals with SCI.

      It is unclear if a longer RT program greater than 12 weeks would provide additional benefits
      to Veterans with SCI. It is also unknown whether enhancing the decline anabolic homeostasis
      by providing testosterone (T) replacement therapy (TRT) would reverse body composition and
      metabolic profile changes in Veterans with SCI. The major research goal of this proposal is
      to investigate the effects of 16 weeks of evoked RT+TRT vs. TRT on body composition (muscle
      CSA, VAT, %FM) and the metabolic profiles (glucose and lipid metabolism) in individuals with
      motor complete SCI. To address this goal, surface NMES accompanied with ankle weights will be
      conducted twice weekly to exercise the knee extensor skeletal muscle groups from sitting
      position. After 4 weeks of delayed entry approach, participants (n =24) will be randomly
      assigned into RT+TRT (n =12) or TRT (n =12) groups. The TRT will be provided via transdermal
      T patches that will be alternated on both shoulders over the course of the study. The
      investigators also propose to study the effects of detraining on body composition and
      metabolic profiles.

      The research plan includes three specific aims

      Specific aim 1 will demonstrate the effects of NMES RT and/or Testosterone patches (Tp) on
      the CSA of thighs and legs skeletal muscle groups, percentage FFM, and the CSA of VAT,
      intramuscular fat and percentage FM after 16 weeks of training+Tp and 16 weeks of detraining.

      Specific aim 2 will determine the changes in metabolic milieu (resting energy expenditure,
      glucose homeostasis, lipid profile, free fatty acids, serum total and free testosterone and
      IGF-1), and cytokines (c-reactive protein, tumor necrosis factor alpha and IL-6 as
      inflammatory biomarkers) after 16 weeks of training+Tp and detraining.

      Specific aim 3 will determine if 16 weeks of evoked RT and Tp will increase GLUT-4
      concentration, muscle IGF-1 and peroxisome-proliferator-activated receptor-gamma co-activator
      1 (PGC-1) expressions, altered fiber type distribution and enhance the mitochondrial
      enzymatic activities (electron transport chain) compared to Tp only.
    

Intervention name(s): Resistance Training and Testosterone Patches; Testosterone Patches
Intervention type(s): Device; Drug
Intervention description(s): We are going to activate the knee extensor muscle group to lift ankle weights over 16 weeks and we are going to provide Tp to improve anabolic profile.; The investigators will provide Tp patches for 16 weeks for patients with Spinal Cord Injury.
Intervention MeSH terms: Methyltestosterone; Testosterone; Testosterone undecanoate; Testosterone enanthate; Testosterone 17 beta-cypionate
Allocation: Randomized
Intervention model: Factorial Assignment
Masking: Single (Investigator)
Primary purpose: Health Services Research
Keywords: Spinal Cord Injury; Rehabilitation; Electrical Stimulation; Testosterone; Body Composition; Lipid and Glucose profile; Ectopic Adiposity