Musculoskeletal Plasticity After Spinal Cord Injury

Not Applicable

Completed

Conditions: Spinal Cord Injuries

Interventions: Behavioral: Single-session electrically induced exercise
Behavioral: Electrically-induced exercise training

Registration Number: NCT02622295

Lead Sponsor: Richard K Shields

Brief Summary: 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.

Detailed Description: Not available

Recruitment & Eligibility

Status: COMPLETED

Sex: All

Target Recruitment: 71

Inclusion Criteria

Motor complete SCI (AIS A-B)

Exclusion Criteria

Pressure ulcers
Chronic infection
Lower extremity muscle contractures
Deep vein thrombosis
Bleeding disorder
Recent limb fractures
Any comorbid disease known to affect bone metabolism (such as parathyroid dysfunction)
Pregnancy
Anti-osteoporosis medications
Vitamin D supplements
Metformin or other medications for diabetes.

Study & Design

Study Type: INTERVENTIONAL

Study Design: PARALLEL

Arm && Interventions

Group	Intervention	Description
Acute gene regulation	Single-session electrically induced exercise	Adaptations in gene regulation in response to single-session electrically induced exercise
Training Study	Electrically-induced exercise training	Adaptations in gene regulation, metabolic markers, and subject-report metrics in response to up to 3 years of electrically induced exercise

Primary Outcome Measures

Name	Time	Method
Post-training Metabolism: Fasting Insulin	up to 3 years	Pre- and post-training fasting insulin, measured via venipuncture and standard laboratory assays
Acute Gene Regulation: MSTN	3 hours after a single session of electrical stimulation	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.
Acute Gene Regulation: PGC1-alpha	3 hours after a single session of electrical stimulation	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.
Acute Gene Regulation: PDK4	3 hours after a single session of electrical stimulation	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.
Acute Gene Regulation: SDHB	3 hours after a single session of electrical stimulation	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.
Post-training Gene Regulation: MSTN	up to 3 years	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.
Post-training Gene Regulation: PGC1-alpha	up to 3 years	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.
Post-training Gene Regulation: PDK4	up to 3 years	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.
Post-training Gene Regulation: SDHB	up to 3 years	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.
Post-training Metabolism: Fasting Glucose	up to 3 years	Pre- and post-training fasting glucose, measured via venipuncture and standard laboratory assays
Post-training Metabolism: HOMA Score	up to 3 years	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.
Post-training Bone Turnover: Osteocalcin	up to 3 years	Pre- and post-training serum osteocalcin, measured via venipuncture and enzyme-linked immunosorbent assay

Secondary Outcome Measures

Name	Time	Method
Post-training Subject-report Measures: EQ-5D	up to 3 years	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.