Patients with spinal cord injury (SCI) experience metabolic syndrome, diabetes, obesity, pressure ulcers, and cardiovascular disease at far greater rates than the general population. A rehabilitation method to prevent or reverse the systemic metabolic consequences of SCI is a pressing need. The purpose of this study is to determine the dose of muscle activity that can enhance an oxidative muscle phenotype, and improve clinical markers of metabolic and bone turnover health in patients with acute SCI. The long-term goal of this research is to develop exercise-based interventions to prevent secondary health conditions such as diabetes and to ultimately protect health-related quality of life (HRQOL).
Specific Aim 1 : To compare changes in skeletal muscle gene regulation in individuals with acute SCI who receive high muscle force standing (HS), low muscle force standing (LS), passive standing (PS), or usual care - (no stimulation and no standing, NS) for 16 weeks. We hypothesize that mRNA expression for metabolic transcription factors and for genes regulating glycolysis, fatty acid oxidation, tricarboxylic acid cycle, oxidative phosphorylation, and mitochondrial remodeling will support that HS and LS instigate a greater shift toward an oxidative muscle phenotype than PS or NS. A novel finding will be that LS is a powerful regulator of oxidative pathways in skeletal muscle.
Specific Aim 2 : To compare changes in systemic markers of metabolic health and bone turnover in individuals with SCI who receive HS, LS, PS, or NS for 16 weeks. We hypothesize that HS and LS will demonstrate lower glucose/insulin levels and greater glucagon suppression during oral glucose challenge compared to PS and NS. HS and LS will also demonstrate lower HOMA scores, hemoglobin A1c, fibroblast growth factor-21 (FGF21), and glucagon-like peptide 1 (GLP-1). LS will be an effective regulator of systemic markers of metabolism. We also hypothesize that HS will demonstrate higher serum levels of osteocalcin, lower levels of type 1 collagen C-telopeptide (CTX), and lower levels of sclerostin than all other groups (HS>LS>PS>NS), indicating an anti-catabolic effect on bone. As a secondary aim, we will measure secondary health conditions (SHCs), HRQOL, and cost effectiveness. We expect that the HS, LS, and PS groups will all show a trend for improved SHCs and HRQOL compared to usual care. We also expect to see an association between metabolic improvement and improved perception of HRQOL. These observations will support that this intervention has strong feasibility for future clinical translaion.

Public Health Relevance

The purpose of this study is to determine whether electrical muscle stimulation in standing can improve three markers of health in patients with spinal cord injury (SCI): muscle gene expression, bone integrity, and clinical tests for insulin and glucose balance. Participants will stand in a standing frame and receive one of four 'doses' of muscle activity, from complete inactivity to very strong muscle contractions. The results of this study wil help us design an effective, practical, and affordable treatment to protect health and improve quality of life for people with SCI.

Agency
National Institute of Health (NIH)
Institute
Eunice Kennedy Shriver National Institute of Child Health & Human Development (NICHD)
Type
Research Project (R01)
Project #
5R01HD084645-14
Application #
9647486
Study Section
Musculoskeletal Rehabilitation Sciences Study Section (MRS)
Program Officer
Bonner, Joseph Francis
Project Start
2000-09-28
Project End
2020-01-31
Budget Start
2019-02-01
Budget End
2020-01-31
Support Year
14
Fiscal Year
2019
Total Cost
Indirect Cost
Name
University of Iowa
Department
Other Health Professions
Type
Schools of Medicine
DUNS #
062761671
City
Iowa City
State
IA
Country
United States
Zip Code
52242
Cole, Keith R; Dudley-Javoroski, Shauna; Shields, Richard K (2018) Hybrid stimulation enhances torque as a function of muscle fusion in human paralyzed and non-paralyzed skeletal muscle. J Spinal Cord Med :1-9
Woelfel, Jessica R; Dudley-Javoroski, Shauna; Shields, Richard K (2018) Precision Physical Therapy: Exercise, the Epigenome, and the Heritability of Environmentally Modified Traits. Phys Ther 98:946-952
Shields, Richard K (2017) Turning Over the Hourglass. Phys Ther 97:949-963
Woelfel, Jessica R; Kimball, Amy L; Yen, Chu-Ling et al. (2017) Low-Force Muscle Activity Regulates Energy Expenditure after Spinal Cord Injury. Med Sci Sports Exerc 49:870-878
Yen, Chu-Ling; McHenry, Colleen L; Petrie, Michael A et al. (2017) Vibration training after chronic spinal cord injury: Evidence for persistent segmental plasticity. Neurosci Lett 647:129-132
Oza, Preeti D; Dudley-Javoroski, Shauna; Shields, Richard K (2017) Modulation of H-Reflex Depression with Paired-Pulse Stimulation in Healthy Active Humans. Rehabil Res Pract 2017:5107097
Oza, Preeti D; Dudley-Javoroski, Shauna; Shields, Richard K (2017) Dynamic Fatigue Does Not Alter Soleus H-Reflexes Conditioned by Homonymous or Heteronymous Pathways. Motor Control 21:345-358
Abode-Iyamah, Kingsley O; Viljoen, Stephanus V; McHenry, Colleen L et al. (2016) Effect of Surgery on Gait and Sensory Motor Performance in Patients With Cervical Spondylotic Myelopathy. Neurosurgery 79:701-707
Abode-Iyamah, Kingsley O; Viljoen, Steve V; McHenry, Colleen L et al. (2016) Effect of Surgery on Gait and Sensory Motor Performance in Patients With Cervical Spondylotic Myelopathy. Neurosurgery :
Petrie, Michael A; Kimball, Amy L; McHenry, Colleen L et al. (2016) Distinct Skeletal Muscle Gene Regulation from Active Contraction, Passive Vibration, and Whole Body Heat Stress in Humans. PLoS One 11:e0160594

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