Trial Outcomes & Findings for Long Duration Activity and Metabolic Control After Spinal Cord Injury (NCT NCT03139344)

Results Overview

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.

Recruitment status

COMPLETED

Study phase

NA

Target enrollment

89 participants

Primary outcome timeframe

3 hours after a single session of electrical stimulation

Results posted on

2023-02-16

Participant Flow

Participant milestones

Participant milestones
Measure	Acute Gene Regulation: Low Frequency Adaptations in gene regulation in response to single-session low-frequency exercise. Low-frequency Exercise: The quadriceps/hamstrings will perform exercise via the application of low-frequency electrical stimulation.	Acute Gene Regulation: High Frequency Adaptations in gene regulation in response to single-session high-frequency exercise. High-frequency Exercise: The quadriceps/hamstrings will perform exercise via the application of high-frequency electrical stimulation.	Training Study: Low Frequency Adaptations in gene regulation, systemic metabolic markers, and patient-report metrics in response to training with low-frequency exercise. Low-frequency Exercise: The quadriceps/hamstrings will perform exercise via the application of low-frequency electrical stimulation.	Training Study: High Frequency Adaptations in gene regulation in response to training with high-frequency exercise. High-frequency Exercise: The quadriceps/hamstrings will perform exercise via the application of high-frequency electrical stimulation.	Comparator Cohort Participants will undergo selected outcome measures to provide comparison values for Experimental arms.
Overall Study STARTED	28	12	21	10	18
Overall Study COMPLETED	28	12	21	10	18
Overall Study NOT COMPLETED	0	0	0	0	0

Reasons for withdrawal

Withdrawal data not reported

Baseline Characteristics

Long Duration Activity and Metabolic Control After Spinal Cord Injury

Baseline characteristics by cohort

Baseline characteristics by cohort
Measure	Acute Gene Regulation: Low Frequency n=28 Participants Adaptations in gene regulation in response to single-session low-frequency exercise. Low-frequency Exercise: The quadriceps/hamstrings will perform exercise via the application of low-frequency electrical stimulation.	Acute Gene Regulation: High Frequency n=12 Participants Adaptations in gene regulation in response to single-session high-frequency exercise. High-frequency Exercise: The quadriceps/hamstrings will perform exercise via the application of high-frequency electrical stimulation.	Training Study: Low Frequency n=21 Participants Adaptations in gene regulation, systemic metabolic markers, and patient-report metrics in response to training with low-frequency exercise. Low-frequency Exercise: The quadriceps/hamstrings will perform exercise via the application of low-frequency electrical stimulation.	Training Study: High Frequency n=10 Participants Adaptations in gene regulation in response to training with high-frequency exercise. High-frequency Exercise: The quadriceps/hamstrings will perform exercise via the application of high-frequency electrical stimulation.	Comparator Cohort n=18 Participants Participants will undergo selected outcome measures to provide comparison values for Experimental arms.	Total n=89 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	0 Participants n=4 Participants	0 Participants n=21 Participants	0 Participants n=8 Participants
Age, Categorical Between 18 and 65 years	28 Participants n=5 Participants	12 Participants n=7 Participants	21 Participants n=5 Participants	10 Participants n=4 Participants	18 Participants n=21 Participants	89 Participants n=8 Participants
Age, Categorical >=65 years	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants	0 Participants n=4 Participants	0 Participants n=21 Participants	0 Participants n=8 Participants
Sex: Female, Male Female	10 Participants n=5 Participants	4 Participants n=7 Participants	8 Participants n=5 Participants	3 Participants n=4 Participants	4 Participants n=21 Participants	29 Participants n=8 Participants
Sex: Female, Male Male	18 Participants n=5 Participants	8 Participants n=7 Participants	13 Participants n=5 Participants	7 Participants n=4 Participants	14 Participants n=21 Participants	60 Participants n=8 Participants
Ethnicity (NIH/OMB) Hispanic or Latino	1 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants	0 Participants n=4 Participants	1 Participants n=21 Participants	2 Participants n=8 Participants
Ethnicity (NIH/OMB) Not Hispanic or Latino	27 Participants n=5 Participants	12 Participants n=7 Participants	21 Participants n=5 Participants	10 Participants n=4 Participants	17 Participants n=21 Participants	87 Participants n=8 Participants
Ethnicity (NIH/OMB) Unknown or Not Reported	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants	0 Participants n=4 Participants	0 Participants n=21 Participants	0 Participants n=8 Participants
Race (NIH/OMB) American Indian or Alaska Native	1 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants	0 Participants n=4 Participants	0 Participants n=21 Participants	1 Participants n=8 Participants
Race (NIH/OMB) Asian	2 Participants n=5 Participants	0 Participants n=7 Participants	2 Participants n=5 Participants	0 Participants n=4 Participants	0 Participants n=21 Participants	4 Participants n=8 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	0 Participants n=4 Participants	0 Participants n=21 Participants	0 Participants n=8 Participants
Race (NIH/OMB) Black or African American	2 Participants n=5 Participants	1 Participants n=7 Participants	1 Participants n=5 Participants	0 Participants n=4 Participants	1 Participants n=21 Participants	5 Participants n=8 Participants
Race (NIH/OMB) White	23 Participants n=5 Participants	11 Participants n=7 Participants	18 Participants n=5 Participants	10 Participants n=4 Participants	17 Participants n=21 Participants	79 Participants n=8 Participants
Race (NIH/OMB) More than one race	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants	0 Participants n=4 Participants	0 Participants n=21 Participants	0 Participants n=8 Participants
Race (NIH/OMB) Unknown or Not Reported	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants	0 Participants n=4 Participants	0 Participants n=21 Participants	0 Participants n=8 Participants
Region of Enrollment United States	28 participants n=5 Participants	12 participants n=7 Participants	21 participants n=5 Participants	10 participants n=4 Participants	18 participants n=21 Participants	89 participants n=8 Participants
Quadriplegia versus Paraplegia Quadriplegia	8 Participants n=5 Participants	4 Participants n=7 Participants	6 Participants n=5 Participants	2 Participants n=4 Participants	6 Participants n=21 Participants	26 Participants n=8 Participants
Quadriplegia versus Paraplegia Paraplegia	20 Participants n=5 Participants	8 Participants n=7 Participants	15 Participants n=5 Participants	8 Participants n=4 Participants	12 Participants n=21 Participants	63 Participants n=8 Participants

PRIMARY outcome

Timeframe: 3 hours after a single session of electrical stimulation

Population: This outcome measure only pertains to the single-session (3 hour) study arms: Acute Gene Regulation: Low Frequency and Acute Gene Regulation: High Frequency

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.

Outcome measures

Outcome measures
Measure	Acute Gene Regulation: Low Frequency n=28 Participants Adaptations in gene regulation in response to single-session low-frequency exercise. Low-frequency Exercise: The quadriceps/hamstrings will perform exercise via the application of low-frequency electrical stimulation.	Acute Gene Regulation: High Frequency n=12 Participants Adaptations in gene regulation in response to single-session high-frequency exercise. High-frequency Exercise: The quadriceps/hamstrings will perform exercise via the application of high-frequency electrical stimulation.
Acute Gene Regulation: NR4A3 mRNA Expression Pre and Post-Stimulation Pre-Stimulation	3.235 arbitrary units Standard Deviation 0.81	2.711 arbitrary units Standard Deviation 0.49
Acute Gene Regulation: NR4A3 mRNA Expression Pre and Post-Stimulation Post-Stimulation	6.286 arbitrary units Standard Deviation 0.78	5.772 arbitrary units Standard Deviation 0.49

PRIMARY outcome

Timeframe: 3 hours after a single session of electrical stimulation

Population: This outcome measure only pertains to the single-session (3 hour) study arms: Acute Gene Regulation: Low Frequency and Acute Gene Regulation: High Frequency

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.

Outcome measures

Outcome measures
Measure	Acute Gene Regulation: Low Frequency n=28 Participants Adaptations in gene regulation in response to single-session low-frequency exercise. Low-frequency Exercise: The quadriceps/hamstrings will perform exercise via the application of low-frequency electrical stimulation.	Acute Gene Regulation: High Frequency n=12 Participants Adaptations in gene regulation in response to single-session high-frequency exercise. High-frequency Exercise: The quadriceps/hamstrings will perform exercise via the application of high-frequency electrical stimulation.
Acute Gene Regulation: PGC1-alpha mRNA Expression Pre and Post-Stimulation Pre-Stimulation	5.37 arbitrary units Standard Deviation 0.48	4.92 arbitrary units Standard Deviation 0.30
Acute Gene Regulation: PGC1-alpha mRNA Expression Pre and Post-Stimulation Post-Stimulation	6.72 arbitrary units Standard Deviation 0.39	6.43 arbitrary units Standard Deviation 0.30

PRIMARY outcome

Timeframe: 3 hours after a single session of electrical stimulation

Population: This outcome measure only pertains to the single-session (3 hour) study arms: Acute Gene Regulation: Low Frequency and Acute Gene Regulation: High Frequency

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.

Outcome measures

Outcome measures
Measure	Acute Gene Regulation: Low Frequency n=28 Participants Adaptations in gene regulation in response to single-session low-frequency exercise. Low-frequency Exercise: The quadriceps/hamstrings will perform exercise via the application of low-frequency electrical stimulation.	Acute Gene Regulation: High Frequency n=12 Participants Adaptations in gene regulation in response to single-session high-frequency exercise. High-frequency Exercise: The quadriceps/hamstrings will perform exercise via the application of high-frequency electrical stimulation.
Acute Gene Regulation: ABRA mRNA Expression Pre and Post-Stimulation Pre-Stimulation	6.76 arbitrary units Standard Deviation 0.993	5.63 arbitrary units Standard Deviation 0.34
Acute Gene Regulation: ABRA mRNA Expression Pre and Post-Stimulation Post-Stimulation	8.61 arbitrary units Standard Deviation 0.76	7.71 arbitrary units Standard Deviation 0.34

PRIMARY outcome

Timeframe: 3 hours after a single session of electrical stimulation

Population: This outcome measure only pertains to the single-session (3 hour) study arms: Acute Gene Regulation: Low Frequency and Acute Gene Regulation: High Frequency

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.

Outcome measures

Outcome measures
Measure	Acute Gene Regulation: Low Frequency n=28 Participants Adaptations in gene regulation in response to single-session low-frequency exercise. Low-frequency Exercise: The quadriceps/hamstrings will perform exercise via the application of low-frequency electrical stimulation.	Acute Gene Regulation: High Frequency n=12 Participants Adaptations in gene regulation in response to single-session high-frequency exercise. High-frequency Exercise: The quadriceps/hamstrings will perform exercise via the application of high-frequency electrical stimulation.
Acute Gene Regulation: PDK4 mRNA Expression Pre and Post-Stimulation Pre-Stimulation	6.64 arbitrary units Standard Deviation 0.38	6.46 arbitrary units Standard Deviation 0.44
Acute Gene Regulation: PDK4 mRNA Expression Pre and Post-Stimulation Post-Stimulation	7.23 arbitrary units Standard Deviation 0.38	7.45 arbitrary units Standard Deviation 0.44

PRIMARY outcome

Timeframe: 6 months

Population: This outcome measure only pertains to the Training study arms: Training Study: Low Frequency and Training Study: High Frequency.

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.

Outcome measures

Outcome measures
Measure	Acute Gene Regulation: Low Frequency n=21 Participants Adaptations in gene regulation in response to single-session low-frequency exercise. Low-frequency Exercise: The quadriceps/hamstrings will perform exercise via the application of low-frequency electrical stimulation.	Acute Gene Regulation: High Frequency n=10 Participants Adaptations in gene regulation in response to single-session high-frequency exercise. High-frequency Exercise: The quadriceps/hamstrings will perform exercise via the application of high-frequency electrical stimulation.
Post-training Gene Regulation: MYH6 mRNA Expression Baseline and Post-Training Baseline	6.61 arbitrary units Standard Deviation 0.71	5.38 arbitrary units Standard Deviation 0.69
Post-training Gene Regulation: MYH6 mRNA Expression Baseline and Post-Training Post-Training	7.10 arbitrary units Standard Deviation 0.88	6.58 arbitrary units Standard Deviation 0.69

PRIMARY outcome

Timeframe: 6 months

Population: This outcome measure only pertains to the Training study arms: Training Study: Low Frequency and Training Study: High Frequency.

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.

Outcome measures

Outcome measures
Measure	Acute Gene Regulation: Low Frequency n=21 Participants Adaptations in gene regulation in response to single-session low-frequency exercise. Low-frequency Exercise: The quadriceps/hamstrings will perform exercise via the application of low-frequency electrical stimulation.	Acute Gene Regulation: High Frequency n=10 Participants Adaptations in gene regulation in response to single-session high-frequency exercise. High-frequency Exercise: The quadriceps/hamstrings will perform exercise via the application of high-frequency electrical stimulation.
Post-training Gene Regulation: MYL3 mRNA Expression Baseline and Post-Training Post-Training	8.01 arbitrary units Standard Deviation 1.08	7.96 arbitrary units Standard Deviation 0.81
Post-training Gene Regulation: MYL3 mRNA Expression Baseline and Post-Training Baseline	7.37 arbitrary units Standard Deviation 0.87	6.38 arbitrary units Standard Deviation 0.81

PRIMARY outcome

Timeframe: 6 months

Population: This outcome measure only pertains to the Training study arms: Training Study: Low Frequency and Training Study: High Frequency.

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.

Outcome measures

Outcome measures
Measure	Acute Gene Regulation: Low Frequency n=21 Participants Adaptations in gene regulation in response to single-session low-frequency exercise. Low-frequency Exercise: The quadriceps/hamstrings will perform exercise via the application of low-frequency electrical stimulation.	Acute Gene Regulation: High Frequency n=10 Participants Adaptations in gene regulation in response to single-session high-frequency exercise. High-frequency Exercise: The quadriceps/hamstrings will perform exercise via the application of high-frequency electrical stimulation.
Post-training Gene Regulation: MYH7 mRNA Expression Baseline and Post-Training Baseline	8.55 arbitrary units Standard Deviation 1.1	7.16 arbitrary units Standard Deviation 0.88
Post-training Gene Regulation: MYH7 mRNA Expression Baseline and Post-Training Post-Training	9.43 arbitrary units Standard Deviation 1.4	8.85 arbitrary units Standard Deviation 0.88

PRIMARY outcome

Timeframe: 6 months

Population: This outcome measure only pertains to the Training study arms: Training Study: Low Frequency and Training Study: High Frequency.

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.