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 health and bone turnover in patients with 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 (QOL). Specific Aim 1: To compare changes in skeletal muscle gene regulation in individuals who receive high frequency (HF) active-resisted stance and low frequency (LF) active-resisted stance for 3 years. Hypothesis 1: The expression of genes regulating skeletal muscle metabolism will support that HF and LF both instigate a shift toward an oxidative muscle phenotype. A novel finding will be that LF 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 HF or LF for 3 years. Hypothesis 2: HF and LF will both reduce glucose/insulin levels and HOMA (homeostasis model assessment) score. Secondary Aim: To measure subject-reported QOL using the EQ-5D survey metric. Hypothesis 3: HF and LF subjects will show a trend toward improved self-reported QOL after 3 years. There will be an association between metabolic improvement and improved perception of QOL. These observations will support that this intervention has strong feasibility for future clinical translation.
Study Type
INTERVENTIONAL
Allocation
NON_RANDOMIZED
Purpose
BASIC_SCIENCE
Masking
NONE
Enrollment
71
A single session of electrically induced exercise to the quadriceps and hamstring muscle groups of people with paralysis.
Multiple sessions of electrically induced exercise to the quadriceps and hamstring muscle groups for up to 3 years in people with paralysis.
University of Iowa
Iowa City, Iowa, United States
Acute Gene Regulation: MSTN
Acute post-stimulation effect upon skeletal muscle myostatin (MSTN) expression, measured via muscle biopsy and exon array analysis. Probe summarization and probe set normalization were performed using robust multichip average, which included background correction, quantile normalization, log2 transformation and median polish probe set summarization. 0 represents no mRNA expression and higher values represent greater expression compared to all genes in the microarray.
Time frame: 3 hours after a single session of electrical stimulation
Acute Gene Regulation: PGC1-alpha
Acute post-stimulation effect upon skeletal muscle peroxisome proliferator-activated receptor gamma coactivator alpha (PGC1-alpha) expression, measured via muscle biopsy and exon array analysis. Probe summarization and probe set normalization were performed using robust multichip average, which included background correction, quantile normalization, log2 transformation and median polish probe set summarization. 0 represents no mRNA expression and higher values represent greater expression compared to all genes in the microarray.
Time frame: 3 hours after a single session of electrical stimulation
Acute Gene Regulation: PDK4
Acute post-stimulation effect upon skeletal muscle pyruvate dehydrogenase kinase, isozyme 4 (PDK4-alpha) expression, measured via muscle biopsy and exon array analysis. Probe summarization and probe set normalization were performed using robust multichip average, which included background correction, quantile normalization, log2 transformation and median polish probe set summarization. 0 represents no mRNA expression and higher values represent greater expression compared to all genes in the microarray.
Time frame: 3 hours after a single session of electrical stimulation
Acute Gene Regulation: SDHB
Acute post-stimulation effect upon skeletal muscle succinate dehydrogenase-B (SDHB) expression, measured via muscle biopsy and exon array analysis. Probe summarization and probe set normalization were performed using robust multichip average, which included background correction, quantile normalization, log2 transformation and median polish probe set summarization. 0 represents no mRNA expression and higher values represent greater expression compared to all genes in the microarray.
Time frame: 3 hours after a single session of electrical stimulation
Post-training Gene Regulation: MSTN
Pre- and post-training skeletal muscle myostatin (MSTN) expression, measured via muscle biopsy and exon array analysis. Probe summarization and probe set normalization were performed using robust multichip average, which included background correction, quantile normalization, log2 transformation and median polish probe set summarization. 0 represents no mRNA expression and higher values represent greater expression compared to all genes in the microarray.
Time frame: up to 3 years
Post-training Gene Regulation: PGC1-alpha
Pre- and post-training skeletal muscle peroxisome proliferator-activated receptor gamma coactivator alpha (PGC1-alpha) expression, measured via muscle biopsy and exon array analysis. Probe summarization and probe set normalization were performed using robust multichip average, which included background correction, quantile normalization, log2 transformation and median polish probe set summarization. 0 represents no mRNA expression and higher values represent greater expression compared to all genes in the microarray.
Time frame: up to 3 years
Post-training Gene Regulation: PDK4
Pre- and post-training skeletal muscle pyruvate dehydrogenase kinase, isozyme 4 (PDK4-alpha) expression, measured via muscle biopsy and exon array analysis. Probe summarization and probe set normalization were performed using robust multichip average, which included background correction, quantile normalization, log2 transformation and median polish probe set summarization. 0 represents no mRNA expression and higher values represent greater expression compared to all genes in the microarray.
Time frame: up to 3 years
Post-training Gene Regulation: SDHB
Pre- and post-training skeletal muscle succinate dehydrogenase-B (SDHB) expression, measured via muscle biopsy and exon array analysis. Probe summarization and probe set normalization were performed using robust multichip average, which included background correction, quantile normalization, log2 transformation and median polish probe set summarization. 0 represents no mRNA expression and higher values represent greater expression compared to all genes in the microarray.
Time frame: up to 3 years
Post-training Metabolism: Fasting Glucose
Pre- and post-training fasting glucose, measured via venipuncture and standard laboratory assays
Time frame: up to 3 years
Post-training Metabolism: Fasting Insulin
Pre- and post-training fasting insulin, measured via venipuncture and standard laboratory assays
Time frame: up to 3 years
Post-training Metabolism: HOMA Score
Pre- and post-training HOMA score, calculated via the Homeostasis Model Assessment equation. Maximum/minimum values: not applicable. Scores \>2 are indicative of insulin resistance.
Time frame: up to 3 years
Post-training Bone Turnover: Osteocalcin
Pre- and post-training serum osteocalcin, measured via venipuncture and enzyme-linked immunosorbent assay
Time frame: up to 3 years
Post-training Subject-report Measures: EQ-5D
Pre- and post-training QALY (quality-adjusted life-years) via the EQ-5D subject-report survey instrument. Scale ranges from -0.287 to 0.992. Higher values indicated a higher self-perceived health state.
Time frame: up to 3 years
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