Musculoskeletal Plasticity After Spinal Cord Injury

Sponsor

Richard K Shields (Other)

Overall Status

Completed

CT.gov ID

NCT02622295

Collaborator

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

Enrollment

Location

Arms

78.6

Actual Duration (Months)

0.9

Patients Per Site Per Month

Study Details

Study Description

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.

Condition or Disease	Intervention/Treatment	Phase
Spinal Cord Injuries	Behavioral: Single-session electrically induced exercise Behavioral: Electrically-induced exercise training	N/A

Study Design

Study Type:

Interventional

Actual Enrollment :

71 participants

Allocation:

Non-Randomized

Intervention Model:

Parallel Assignment

Masking:

None (Open Label)

Primary Purpose:

Basic Science

Official Title:

Musculoskeletal Plasticity After Spinal Cord Injury

Actual Study Start Date :

May 1, 2015

Actual Primary Completion Date :

Nov 18, 2021

Actual Study Completion Date :

Nov 18, 2021

Arms and Interventions

Arm	Intervention/Treatment
Experimental: Acute gene regulation Adaptations in gene regulation in response to single-session electrically induced exercise	Behavioral: Single-session electrically induced exercise A single session of electrically induced exercise to the quadriceps and hamstring muscle groups of people with paralysis.
Experimental: Training Study Adaptations in gene regulation, metabolic markers, and subject-report metrics in response to up to 3 years of electrically induced exercise	Behavioral: Electrically-induced exercise training Multiple sessions of electrically induced exercise to the quadriceps and hamstring muscle groups for up to 3 years in people with paralysis.

Arm

Intervention/Treatment

Experimental: Acute gene regulation

Adaptations in gene regulation in response to single-session electrically induced exercise

Behavioral: Single-session electrically induced exercise

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

Experimental: Training Study

Adaptations in gene regulation, metabolic markers, and subject-report metrics in response to up to 3 years of electrically induced exercise

Behavioral: Electrically-induced exercise training

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

Outcome Measures

Primary Outcome Measures

Acute gene regulation: MSTN [3 hours]
Acute post-stimulation effect upon skeletal muscle myostatin (MSTN) expression, measured via muscle biopsy and exon array analysis
Acute gene regulation: PGC1-alpha [3 hours]
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
Acute gene regulation: PDK4 [3 hours]
Acute post-stimulation effect upon skeletal muscle pyruvate dehydrogenase kinase, isozyme 4 (PDK4-alpha) expression, measured via muscle biopsy and exon array analysis
Acute gene regulation: SDHB [3 hours]
Acute post-stimulation effect upon skeletal muscle succinate dehydrogenase-B (SDHB) expression, measured via muscle biopsy and exon array analysis
Post-training gene regulation: MSTN [up to 3 years]
Change from baseline in skeletal muscle myostatin (MSTN) expression, measured via muscle biopsy and exon array analysis
Post-training gene regulation: PGC1-alpha [up to 3 years]
Change from baseline in skeletal muscle peroxisome proliferator-activated receptor gamma coactivator alpha (PGC1-alpha) expression, measured via muscle biopsy and exon array analysis
Post-training gene regulation: PDK4 [up to 3 years]
Change from baseline in skeletal muscle pyruvate dehydrogenase kinase, isozyme 4 (PDK4-alpha) expression, measured via muscle biopsy and exon array analysis
Post-training gene regulation: SDHB [up to 3 years]
Change from baseline in skeletal muscle succinate dehydrogenase-B (SDHB) expression, measured via muscle biopsy and exon array analysis
Post-training metabolism: fasting glucose [up to 3 years]
Change from baseline in fasting glucose, measured via venipuncture and standard laboratory assays
Post-training metabolism: fasting insulin [up to 3 years]
Change from baseline in fasting insulin, measured via venipuncture and standard laboratory assays
Post-training metabolism: HOMA score [up to 3 years]
Change from baseline in HOMA score, calculated via the Homeostasis Model Assessement equation
Post-training bone turnover: osteocalcin [up to 3 years]
Change from baseline in serum osteocalcin, measured via venipuncture and enzyme-linked immunosorbent assay

Secondary Outcome Measures

Post-training subject-report measures: EQ-5D [up to 3 years]
Change from baseline in QALY (quality-adjusted life-years) via the EQ-5D subject-report survey instrument

Eligibility Criteria

Criteria

Ages Eligible for Study:

21 Years to 60 Years

Sexes Eligible for Study:

All

Accepts Healthy Volunteers:

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.