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NCT03139344

Long Duration Activity and Metabolic Control After Spinal Cord Injury

Completed NA Results posted Last updated 16 February 2023
What this trial tests

NA trial testing Low-frequency Exercise in Spinal Cord Injuries in 89 participants. Completed in 1 April 2022.

Timeline
1 August 2015
Primary endpoint
1 April 2022
1 April 2022

Quick facts

Lead sponsorRichard K Shields
PhaseNA
StatusCompleted
Study typeINTERVENTIONAL
Allocationnon randomized
Designparallel
Maskingnone
Primary purposebasic science
Enrollment89
Start date1 August 2015
Primary completion1 April 2022
Estimated completion1 April 2022
Sites1 location across United States

Drugs / interventions tested

Conditions studied

Sponsor

Richard K Shields

Who can join

18 and older, any sex, with Spinal Cord Injuries. Patients with the condition only — healthy volunteers not accepted.

Results — posted to ClinicalTrials.gov

Per-arm endpoint measurements with 95% confidence intervals where reported. Source: trial results section.

Acute Gene Regulation: NR4A3 mRNA Expression Pre and Post-Stimulation Primary · 3 hours after a single session of electrical stimulation

Acute post-stimulation effect upon skeletal muscle nuclear receptor subfamily 4 group A member 3 (NR4A3) 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.

Pre-Stimulation
GroupValue95% CI
Acute Gene Regulation: Low Frequency3.235± 0.81
Acute Gene Regulation: High Frequency2.711± 0.49
Post-Stimulation
GroupValue95% CI
Acute Gene Regulation: Low Frequency6.286± 0.78
Acute Gene Regulation: High Frequency5.772± 0.49
Acute Gene Regulation: PGC1-alpha mRNA Expression Pre and Post-Stimulation Primary · 3 hours after a single session of electrical stimulation

Acute post-stimulation effect upon skeletal muscle peroxisome proliferator-activated gamma coactivator (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.

Pre-Stimulation
GroupValue95% CI
Acute Gene Regulation: Low Frequency5.37± 0.48
Acute Gene Regulation: High Frequency4.92± 0.30
Post-Stimulation
GroupValue95% CI
Acute Gene Regulation: Low Frequency6.72± 0.39
Acute Gene Regulation: High Frequency6.43± 0.30
Acute Gene Regulation: ABRA mRNA Expression Pre and Post-Stimulation Primary · 3 hours after a single session of electrical stimulation

Acute post-stimulation effect upon skeletal muscle actin binding Rho activating protein (ABRA) 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.

Pre-Stimulation
GroupValue95% CI
Acute Gene Regulation: Low Frequency6.76± 0.993
Acute Gene Regulation: High Frequency5.63± 0.34
Post-Stimulation
GroupValue95% CI
Acute Gene Regulation: Low Frequency8.61± 0.76
Acute Gene Regulation: High Frequency7.71± 0.34
Acute Gene Regulation: PDK4 mRNA Expression Pre and Post-Stimulation Primary · 3 hours after a single session of electrical stimulation

Acute post-stimulation effect upon skeletal muscle pyruvate dehydrogenase kinase 4 (PDK4) 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.

Pre-Stimulation
GroupValue95% CI
Acute Gene Regulation: Low Frequency6.64± 0.38
Acute Gene Regulation: High Frequency6.46± 0.44
Post-Stimulation
GroupValue95% CI
Acute Gene Regulation: Low Frequency7.23± 0.38
Acute Gene Regulation: High Frequency7.45± 0.44
Post-training Gene Regulation: MYH6 mRNA Expression Baseline and Post-Training Primary · 6 months

Pre- and post-training skeletal muscle myosin heavy chain 6 (MYH6) 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.

Baseline
GroupValue95% CI
Training Study: Low Frequency6.61± 0.71
Training Study: High Frequency5.38± 0.69
Post-Training
GroupValue95% CI
Training Study: Low Frequency7.10± 0.88
Training Study: High Frequency6.58± 0.69
Post-training Gene Regulation: MYL3 mRNA Expression Baseline and Post-Training Primary · 6 months

Pre- and post-training skeletal muscle myosin light chain 3 (MYL3) 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.

Baseline
GroupValue95% CI
Training Study: Low Frequency7.37± 0.87
Training Study: High Frequency6.38± 0.81
Post-Training
GroupValue95% CI
Training Study: Low Frequency8.01± 1.08
Training Study: High Frequency7.96± 0.81
Post-training Gene Regulation: MYH7 mRNA Expression Baseline and Post-Training Primary · 6 months

Pre- and post-training skeletal muscle myosin heavy chain 7 (MYH7) 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.

Baseline
GroupValue95% CI
Training Study: Low Frequency8.55± 1.1
Training Study: High Frequency7.16± 0.88
Post-Training
GroupValue95% CI
Training Study: Low Frequency9.43± 1.4
Training Study: High Frequency8.85± 0.88
Post-training Gene Regulation: ACTN3 mRNA Expression Baseline and Post-Training Primary · 6 months

Pre- and post-training skeletal muscle actin 3 (ACTN3) 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.

Baseline
GroupValue95% CI
Training Study: Low Frequency8.95± 0.79
Training Study: High Frequency8.51± 0.74
Post-Training
GroupValue95% CI
Training Study: Low Frequency8.20± 0.71
Training Study: High Frequency7.12± 0.74
Post-training Metabolism: Fasting Insulin Primary · 6 months

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

Pre-Training
GroupValue95% CI
Training Study: Low Frequency19.245± 16.387
Post-Training
GroupValue95% CI
Training Study: Low Frequency8.305± 3.407
Post-training Metabolism: Fasting Glucose Primary · 6 months

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

Pre-Training
GroupValue95% CI
Training Study: Low Frequency94.727± 10.725
Post-Training
GroupValue95% CI
Training Study: Low Frequency91.091± 14.223
Post-training Metabolism: Fasting Glucose-insulin Ratio Primary · 6 months

Pre- and post-training ratio of fasting glucose to fasting insulin, measured via venipuncture and standard laboratory assays

Pre-Training
GroupValue95% CI
Training Study: Low Frequency8.649± 5.573
Post-Training
GroupValue95% CI
Training Study: Low Frequency11.274± 5.417
Post-training Metabolism: Fasting Hemoglobin A1c (HBA1c) Primary · 6 months

Pre- and post-training fasting Hemoglobin A1C (HbA1c), measured via venipuncture and standard laboratory assays

Pre-training
GroupValue95% CI
Training Study: Low Frequency4.227± 1.030
Post-training
GroupValue95% CI
Training Study: Low Frequency3.970± 0.946

Sponsor's own description

Skeletal muscle is the largest endocrine organ in the body, playing an indispensable role in glucose homeostasis. Spinal cord injury (SCI) prevents skeletal muscle from carrying out this important function. Dysregulation of glucose metabolism precipitates high rates of metabolic syndrome, diabetes, and other secondary health conditions (SHCs) of SCI. These SHCs exert a negative influence on health-related quality of life (HRQOL). New discoveries support that a low level of activity throughout the day offers a more effective metabolic stimulus than brief, episodic exercise bouts. The proposed study will translate this emerging concept to the population of individuals with SCI by using low-force, long-duration electrical muscle stimulation to subsidize daily activity levels. Recently, we demonstrated that this type of stimulation up-regulates key genes that foster an oxidative, insulin-sensitive phenotype in paralyzed muscle. We will now test whether this type of activity can improve glucose homeostasis and metabolic function in patients with chronic paralysis. We hypothesize that improvements in metabolic function will be accompanied by a reduction in SHCs and a concomitant improvement in self-reported HRQOL. The long-term goal of this research is to develop a rehabilitation strategy to protect the musculoskeletal health, metabolic function, and health-related quality of life of people living with complete SCI.

Publications & conference data

1 peer-reviewed publication reference this trial (live from Europe PMC):

  1. Distinct Genomic Expression Signatures after Low-Force Electrically Induced Exercises in Persons with Spinal Cord Injury.
    Petrie MA, Suneja M, Shields RK. · · 2024 · cited 1× · PMID 39337673 · DOI 10.3390/ijms251810189

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