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Completed

NCT Number: NCT02622295

Musculoskeletal Plasticity After Spinal Cord Injury

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.

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Key information

Conditions

Spinal Cord Injuries Bone Diseases Bone Diseases, Metabolic Central Nervous System Diseases Diabetes Mellitus Endocrine System Diseases Glucose Metabolism Disorders Hyperinsulinism Insulin Resistance Metabolic Diseases Musculoskeletal Diseases Nervous System Diseases Nutritional and Metabolic Diseases Osteoporosis Spinal Cord Diseases Trauma, Nervous System Wounds and Injuries

Age range

21 year–60 year

Sex eligibility

All sexes

Study type

Interventional

Phase

Not applicable

Primary location

University of Iowa

Iowa City, Iowa, 52242, United States

Who can participate

Healthy volunteers accepted: No

Only the study team can determine whether someone qualifies for participation.

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.

Treatment and study plan

Single-session electrically induced exercise

Behavioral

A single session of electrically induced exercise to the quadriceps and hamstring muscle groups of people with paralysis.

Electrically-induced exercise training

Behavioral

Multiple sessions of electrically induced exercise to the quadriceps and hamstring muscle groups for up to 3 years in people with paralysis.

Primary outcomes

  1. Acute Gene Regulation: MSTN

    Time frame: 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.

  2. Acute Gene Regulation: PGC1-alpha

    Time frame: 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.

  3. Acute Gene Regulation: PDK4

    Time frame: 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.

  4. Acute Gene Regulation: SDHB

    Time frame: 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.

  5. Post-training Gene Regulation: MSTN

    Time frame: 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.

  6. Post-training Gene Regulation: PGC1-alpha

    Time frame: 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.

  7. Post-training Gene Regulation: PDK4

    Time frame: 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.

  8. Post-training Gene Regulation: SDHB

    Time frame: 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.

  9. Post-training Metabolism: Fasting Glucose

    Time frame: up to 3 years

    Pre- and post-training fasting glucose, measured via venipuncture and standard laboratory assays

  10. Post-training Metabolism: Fasting Insulin

    Time frame: up to 3 years

    Pre- and post-training fasting insulin, measured via venipuncture and standard laboratory assays

  11. Post-training Metabolism: HOMA Score

    Time frame: 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.

  12. Post-training Bone Turnover: Osteocalcin

    Time frame: up to 3 years

    Pre- and post-training serum osteocalcin, measured via venipuncture and enzyme-linked immunosorbent assay

Secondary outcomes

  1. Post-training Subject-report Measures: EQ-5D

    Time frame: 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.

Sponsors and collaborators

Lead sponsor

Richard K Shields

Other

Collaborators

  • Eunice Kennedy Shriver National Institute of Child Health and Human Development (NICHD)

Registry information

Important dates

Study start
2015
Primary completion
2021
Study completion
2021
First posted
Dec 4, 2015
Registry last updated
Nov 4, 2022

OpenTrials presents study information sourced from ClinicalTrials.gov. The official registry record should be consulted for the latest information.

View the official ClinicalTrials.gov record (opens in a new tab)

This listing is for discovery and informational purposes only. It is not medical advice, does not guarantee that a study is recruiting, and does not determine eligibility. Contact the study team and a qualified healthcare professional when considering participation.

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