Trial Outcomes & Findings for Musculoskeletal Plasticity After Spinal Cord Injury (NCT NCT02622295)

NCT ID: NCT02622295

Last Updated: 2022-11-04

Results Overview

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.

• Recruitment status: COMPLETED
• Study phase: NA
• Target enrollment: 71 participants
• Primary outcome timeframe: 3 hours after a single session of electrical stimulation
• Results posted on: 2022-11-04

Participant Flow

Participant milestones

Measure	Acute Gene Regulation Adaptations in gene regulation in response to single-session electrically induced exercise Single-session electrically induced exercise: A single session of electrically induced exercise to the quadriceps and hamstring muscle groups of people with paralysis.	Training Study Adaptations in gene regulation, metabolic markers, and subject-report metrics in response to up to 3 years of electrically induced exercise 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.
Overall Study STARTED	40	31
Overall Study COMPLETED	40	31
Overall Study NOT COMPLETED	0	0

Reasons for withdrawal

Withdrawal data not reported

Baseline Characteristics

Musculoskeletal Plasticity After Spinal Cord Injury

Baseline characteristics by cohort

Measure	Acute Gene Regulation n=40 Participants Adaptations in gene regulation in response to single-session electrically induced exercise Single-session electrically induced exercise: A single session of electrically induced exercise to the quadriceps and hamstring muscle groups of people with paralysis.	Training Study n=31 Participants Adaptations in gene regulation, metabolic markers, and subject-report metrics in response to up to 3 years of electrically induced exercise 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.	Total n=71 Participants Total of all reporting groups
Age, Categorical <=18 years	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants
Age, Categorical Between 18 and 65 years	40 Participants n=5 Participants	31 Participants n=7 Participants	71 Participants n=5 Participants
Age, Categorical >=65 years	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants
Sex: Female, Male Female	13 Participants n=5 Participants	10 Participants n=7 Participants	23 Participants n=5 Participants
Sex: Female, Male Male	27 Participants n=5 Participants	21 Participants n=7 Participants	48 Participants n=5 Participants
Ethnicity (NIH/OMB) Hispanic or Latino	1 Participants n=5 Participants	0 Participants n=7 Participants	1 Participants n=5 Participants
Ethnicity (NIH/OMB) Not Hispanic or Latino	39 Participants n=5 Participants	31 Participants n=7 Participants	70 Participants n=5 Participants
Ethnicity (NIH/OMB) Unknown or Not Reported	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants
Race (NIH/OMB) American Indian or Alaska Native	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants
Race (NIH/OMB) Asian	3 Participants n=5 Participants	1 Participants n=7 Participants	4 Participants n=5 Participants
Race (NIH/OMB) Native Hawaiian or Other Pacific Islander	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants
Race (NIH/OMB) Black or African American	3 Participants n=5 Participants	2 Participants n=7 Participants	5 Participants n=5 Participants
Race (NIH/OMB) White	34 Participants n=5 Participants	28 Participants n=7 Participants	62 Participants n=5 Participants
Race (NIH/OMB) More than one race	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants
Race (NIH/OMB) Unknown or Not Reported	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants
Region of Enrollment United States	40 participants n=5 Participants	31 participants n=7 Participants	71 participants n=5 Participants
Quadriplegia versus Paraplegia Quadriplegia	14 Participants n=5 Participants	11 Participants n=7 Participants	25 Participants n=5 Participants
Quadriplegia versus Paraplegia Paraplegia	26 Participants n=5 Participants	20 Participants n=7 Participants	46 Participants n=5 Participants

PRIMARY outcome

Timeframe: 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.

Outcome measures

Measure	Acute Gene Regulation n=40 Participants Adaptations in gene regulation in response to single-session electrically induced exercise
Acute Gene Regulation: MSTN Pre-Stimulation	5.49 arbitrary units Standard Deviation 0.633
Acute Gene Regulation: MSTN Post-Stimulation	4.76 arbitrary units Standard Deviation 0.748

PRIMARY outcome

Timeframe: 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.

Outcome measures

Measure	Acute Gene Regulation n=40 Participants Adaptations in gene regulation in response to single-session electrically induced exercise
Acute Gene Regulation: PGC1-alpha Pre-Stimulation	5.23 arbitrary units Standard Deviation 0.486
Acute Gene Regulation: PGC1-alpha Post-Stimulation	6.63 arbitrary units Standard Deviation 0.395

PRIMARY outcome

Timeframe: 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.

Outcome measures

Measure	Acute Gene Regulation n=40 Participants Adaptations in gene regulation in response to single-session electrically induced exercise
Acute Gene Regulation: PDK4 Pre-Stimulation	6.59 arbitrary units Standard Deviation 0.413
Acute Gene Regulation: PDK4 Post-Stimulation	7.29 arbitrary units Standard Deviation 0.416

PRIMARY outcome

Timeframe: 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.

Outcome measures

Measure	Acute Gene Regulation n=40 Participants Adaptations in gene regulation in response to single-session electrically induced exercise
Acute Gene Regulation: SDHB Pre-Stimulation	7.15 arbitrary units Standard Deviation 0.478
Acute Gene Regulation: SDHB Post-Stimulation	7.20 arbitrary units Standard Deviation 0.490

PRIMARY outcome

Timeframe: 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.

Outcome measures

Measure	Acute Gene Regulation n=31 Participants Adaptations in gene regulation in response to single-session electrically induced exercise
Post-training Gene Regulation: MSTN Baseline	5.34 arbitrary units Standard Deviation 0.510
Post-training Gene Regulation: MSTN Post-Training (up to 3 years)	4.78 arbitrary units Standard Deviation 0.668

PRIMARY outcome

Timeframe: 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.

Outcome measures

Measure	Acute Gene Regulation n=31 Participants Adaptations in gene regulation in response to single-session electrically induced exercise
Post-training Gene Regulation: PGC1-alpha Baseline	5.89 arbitrary units Standard Deviation 0.372
Post-training Gene Regulation: PGC1-alpha Post-Training (up to 3 years)	5.90 arbitrary units Standard Deviation 0.337

PRIMARY outcome

Timeframe: 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.

Outcome measures

Measure	Acute Gene Regulation n=31 Participants Adaptations in gene regulation in response to single-session electrically induced exercise
Post-training Gene Regulation: PDK4 Baseline	7.01 arbitrary units Standard Deviation 0.377
Post-training Gene Regulation: PDK4 Post-Training (up to 3 years)	6.87 arbitrary units Standard Deviation 0.372

PRIMARY outcome

Timeframe: 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.

Outcome measures

Measure	Acute Gene Regulation n=31 Participants Adaptations in gene regulation in response to single-session electrically induced exercise
Post-training Gene Regulation: SDHB Baseline	7.22 arbitrary units Standard Deviation 0.456
Post-training Gene Regulation: SDHB Post-Training (up to 3 years)	7.26 arbitrary units Standard Deviation 0.556

PRIMARY outcome

Timeframe: up to 3 years

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

Outcome measures

Measure	Acute Gene Regulation n=10 Participants Adaptations in gene regulation in response to single-session electrically induced exercise
Post-training Metabolism: Fasting Glucose Baseline	95.5 mg/dL Standard Deviation 10.5
Post-training Metabolism: Fasting Glucose Post-Training (up to 3 years)	97.8 mg/dL Standard Deviation 7.7

PRIMARY outcome

Timeframe: up to 3 years

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

Outcome measures

Measure	Acute Gene Regulation n=10 Participants Adaptations in gene regulation in response to single-session electrically induced exercise
Post-training Metabolism: Fasting Insulin Baseline	20.6 microU/mL Standard Deviation 16.7
Post-training Metabolism: Fasting Insulin Post-Training (up to 3 years)	11.8 microU/mL Standard Deviation 8.37

PRIMARY outcome

Timeframe: 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.

Outcome measures

Measure	Acute Gene Regulation n=10 Participants Adaptations in gene regulation in response to single-session electrically induced exercise
Post-training Metabolism: HOMA Score Baseline	2.3 score on a scale Standard Deviation 1.8
Post-training Metabolism: HOMA Score Post-Training (up to 3 years)	1.3 score on a scale Standard Deviation 0.9

PRIMARY outcome

Timeframe: up to 3 years

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

Outcome measures

Measure	Acute Gene Regulation n=10 Participants Adaptations in gene regulation in response to single-session electrically induced exercise
Post-training Bone Turnover: Osteocalcin Baseline	6638.5 pg/mL Standard Deviation 2711.9
Post-training Bone Turnover: Osteocalcin Post-Training (up to 3 years)	6874.1 pg/mL Standard Deviation 3197.5

SECONDARY outcome

Timeframe: 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.

Outcome measures

Measure	Acute Gene Regulation n=11 Participants Adaptations in gene regulation in response to single-session electrically induced exercise
Post-training Subject-report Measures: EQ-5D Baseline	0.296 score on a scale Standard Deviation 0.111
Post-training Subject-report Measures: EQ-5D Post-Training (up to 3 years)	0.265 score on a scale Standard Deviation 0.093

Adverse Events

Acute Gene Regulation

Serious events: 0 serious events

Other events: 0 other events

Deaths: 0 deaths

Training Study

Serious events: 0 serious events

Other events: 0 other events

Deaths: 0 deaths

Serious adverse events

Adverse event data not reported

Other adverse events

Adverse event data not reported

Additional Information

Dr. Richard K. Shields

University of Iowa Department of Physical Therapy and Rehabilitation Science

Phone: 319-335-9791

Email: richard-shields@uiowa.edu

Results disclosure agreements

• Principal investigator is a sponsor employee
• Publication restrictions are in place