Spinal Cord Injuries
Conditions
Keywords
metabolism, exercise, glucose, secondary health conditions, quality of life
Brief summary
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.
Detailed description
Skeletal muscle is a critical organ for regulating glucose and insulin in the body as a whole, and post-spinal cord injury (SCI) adaptations in muscle severely undermine this capacity. Contemporary SCI rehabilitation for people with complete SCI does not intervene to protect the function of paralyzed skeletal muscle as a key regulator of metabolic homeostasis. Through its deleterious effects on multiple systems, metabolic disease is one of the leading sources of morbidity, mortality, and health care cost for this population. In the non-SCI population, pervasive, frequent, low-magnitude muscle contractions can increase energy expenditure by 50.3% above sitting levels. The loss of this component of muscle activity contributes to the energy imbalance and metabolic dysregulation observed in SCI. Subsidizing low-magnitude muscle contractions may offer an important metabolic stimulus for people with SCI. The significance of this study is that it builds on previous work demonstrating healthful transcriptional and translational gene adaptations in response to electrical stimulation training in SCI. These adaptations may initiate improvements in systemic biomarkers of metabolic health and improvements in secondary health conditions and health-related quality of life. In our previous work, we demonstrated that regular electrical stimulation of paralyzed muscle up-regulates PGC-1α, a key transcriptional co-activator for skeletal muscle and metabolic adaptation. Our previous work also indicates that electrical stimulation alters the expression of genes controlling mitochondrial biogenesis. However, we understand very little about the optimal amount of electrically-evoked muscle activity to deliver in order to promote positive metabolic adaptations. Long duration, low force contractions are likely to be most advantageous for promoting metabolic stability in people with chronic SCI, who also have osteoporosis and are unable to receive high force muscle contractions induced by conventional rehabilitation protocols. This study will intervene with a protocol of low-force, long-duration muscle stimulation designed to instigate systemic metabolic adaptations. In the proposed study we hypothesize that gene-level adaptations will yield tissue-level improvements in glucose utilization that facilitate systemic improvements in clinical markers of metabolic control, culminating in fewer secondary health conditions and enhanced health-related quality of life.
Interventions
OTHERLow-frequency Exercise
The quadriceps/hamstrings will perform exercise via the application of low-frequency electrical stimulation.
OTHERHigh-frequency Exercise
The quadriceps/hamstrings will perform exercise via the application of high-frequency electrical stimulation.
Sponsors
Eunice Kennedy Shriver National Institute of Child Health and Human Development (NICHD)
Richard K Shields
Study design
Allocation
NON_RANDOMIZED
Intervention model
PARALLEL
Primary purpose
BASIC_SCIENCE
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
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, pregnancy, metformin or other medications for diabetes
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Acute Gene Regulation: NR4A3 mRNA Expression Pre and Post-Stimulation | 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. |
| Acute Gene Regulation: PGC1-alpha mRNA Expression Pre and Post-Stimulation | 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. |
| Acute Gene Regulation: ABRA mRNA Expression Pre and Post-Stimulation | 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. |
| Acute Gene Regulation: PDK4 mRNA Expression Pre and Post-Stimulation | 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. |
| Post-training Gene Regulation: MYH6 mRNA Expression Baseline and Post-Training | 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. |
| Post-training Gene Regulation: MYL3 mRNA Expression Baseline and Post-Training | 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. |
| Post-training Gene Regulation: MYH7 mRNA Expression Baseline and Post-Training | 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. |
| Post-training Gene Regulation: ACTN3 mRNA Expression Baseline and Post-Training | 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. |
| Post-training Metabolism: Fasting Insulin | 6 months | Pre- and post-training fasting insulin, measured via venipuncture and standard laboratory assays |
| Post-training Metabolism: Fasting Glucose | 6 months | Pre- and post-training fasting glucose, measured via venipuncture and standard laboratory assays |
| Post-training Metabolism: Fasting Glucose-insulin Ratio | 6 months | Pre- and post-training ratio of fasting glucose to fasting insulin, measured via venipuncture and standard laboratory assays |
| Post-training Metabolism: Fasting Hemoglobin A1c (HBA1c) | 6 months | Pre- and post-training fasting Hemoglobin A1C (HbA1c), measured via venipuncture and standard laboratory assays |
| Post-training Metabolism: C-reactive Protein (CRP) | 6 months | Pre- and post-training C-reactive protein (CRP), measured via venipuncture and standard laboratory assays |
| Pre-training Subject-report Measures: PROMIS Physical Health | Baseline | Pre-training Patient Reported Outcomes Measurement Information Systems (PROMIS) Global Health - Physical health T-score Theoretical minimum = 16.2, Theoretical maximum = 67.7, higher scores signify more of the construct being measured (eg. physical health). US population mean = 50, SD = 10. |
| Pre-training Subject Report Measures: PROMIS Mental Health | Baseline | Pre-training Patient Reported Outcomes Measurement Information Systems (PROMIS) Global Health - Mental health T-score Theoretical minimum = 21.2, Theoretical maximum = 67.6, higher scores signify more of the construct being measured (eg. mental health). US population mean = 50, SD = 10. |
| Post-training Subject-report Measures: PROMIS Physical Health | 6 months | Pre- and post-training Patient Reported Outcomes Measurement Information Systems (PROMIS) Global Health - Physical health T-score Theoretical minimum = 16.2, Theoretical maximum = 67.7, higher scores signify more of the construct being measured (eg. physical health). US population mean = 50, SD = 10. |
| Post-training Subject-report Measures: PROMIS Mental Health | 6 months | Pre- and post-training Patient Reported Outcomes Measurement Information Systems (PROMIS) Global Health - Mental health T-score Theoretical minimum = 21.2, Theoretical maximum = 67.6, higher scores signify more of the construct being measured (eg. mental health). US population mean = 50, SD = 10. |
Countries
United States
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| 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. | 28 |
| 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. | 12 |
| 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. | 21 |
| 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. | 10 |
| Comparator Cohort Participants will undergo selected outcome measures to provide comparison values for Experimental arms. | 18 |
| Total | 89 |
Baseline characteristics
| Characteristic | Acute Gene Regulation: Low Frequency | Acute Gene Regulation: High Frequency | Training Study: Low Frequency | Training Study: High Frequency | Comparator Cohort | Total |
|---|---|---|---|---|---|---|
| Age, Categorical <=18 years | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Age, Categorical >=65 years | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Age, Categorical Between 18 and 65 years | 28 Participants | 12 Participants | 21 Participants | 10 Participants | 18 Participants | 89 Participants |
| Ethnicity (NIH/OMB) Hispanic or Latino | 1 Participants | 0 Participants | 0 Participants | 0 Participants | 1 Participants | 2 Participants |
| Ethnicity (NIH/OMB) Not Hispanic or Latino | 27 Participants | 12 Participants | 21 Participants | 10 Participants | 17 Participants | 87 Participants |
| Ethnicity (NIH/OMB) Unknown or Not Reported | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Quadriplegia versus Paraplegia Paraplegia | 20 Participants | 8 Participants | 15 Participants | 8 Participants | 12 Participants | 63 Participants |
| Quadriplegia versus Paraplegia Quadriplegia | 8 Participants | 4 Participants | 6 Participants | 2 Participants | 6 Participants | 26 Participants |
| Race (NIH/OMB) American Indian or Alaska Native | 1 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 1 Participants |
| Race (NIH/OMB) Asian | 2 Participants | 0 Participants | 2 Participants | 0 Participants | 0 Participants | 4 Participants |
| Race (NIH/OMB) Black or African American | 2 Participants | 1 Participants | 1 Participants | 0 Participants | 1 Participants | 5 Participants |
| Race (NIH/OMB) More than one race | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Native Hawaiian or Other Pacific Islander | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Unknown or Not Reported | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) White | 23 Participants | 11 Participants | 18 Participants | 10 Participants | 17 Participants | 79 Participants |
| Region of Enrollment United States | 28 participants | 12 participants | 21 participants | 10 participants | 18 participants | 89 participants |
| Sex: Female, Male Female | 10 Participants | 4 Participants | 8 Participants | 3 Participants | 4 Participants | 29 Participants |
| Sex: Female, Male Male | 18 Participants | 8 Participants | 13 Participants | 7 Participants | 14 Participants | 60 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk | EG002 affected / at risk | EG003 affected / at risk | EG004 affected / at risk |
|---|---|---|---|---|---|
| deaths Total, all-cause mortality | 0 / 28 | 0 / 12 | 0 / 21 | 0 / 10 | 0 / 18 |
| other Total, other adverse events | 0 / 28 | 0 / 12 | 0 / 21 | 0 / 10 | 0 / 18 |
| serious Total, serious adverse events | 0 / 28 | 0 / 12 | 0 / 21 | 0 / 10 | 0 / 18 |
Outcome results
Primary
Acute Gene Regulation: ABRA mRNA Expression Pre and Post-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.
Time frame: 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
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Acute Gene Regulation: Low Frequency | Acute Gene Regulation: ABRA mRNA Expression Pre and Post-Stimulation | Pre-Stimulation | 6.76 arbitrary units | Standard Deviation 0.993 |
| Acute Gene Regulation: Low Frequency | Acute Gene Regulation: ABRA mRNA Expression Pre and Post-Stimulation | Post-Stimulation | 8.61 arbitrary units | Standard Deviation 0.76 |
| Acute Gene Regulation: High Frequency | Acute Gene Regulation: ABRA mRNA Expression Pre and Post-Stimulation | Pre-Stimulation | 5.63 arbitrary units | Standard Deviation 0.34 |
| Acute Gene Regulation: High Frequency | Acute Gene Regulation: ABRA mRNA Expression Pre and Post-Stimulation | Post-Stimulation | 7.71 arbitrary units | Standard Deviation 0.34 |
p-value: 0.011ANOVA
p-value: <0.001ANOVA
Primary
Acute Gene Regulation: NR4A3 mRNA Expression Pre and Post-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.
Time frame: 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
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Acute Gene Regulation: Low Frequency | Acute Gene Regulation: NR4A3 mRNA Expression Pre and Post-Stimulation | Post-Stimulation | 6.286 arbitrary units | Standard Deviation 0.78 |
| Acute Gene Regulation: Low Frequency | Acute Gene Regulation: NR4A3 mRNA Expression Pre and Post-Stimulation | Pre-Stimulation | 3.235 arbitrary units | Standard Deviation 0.81 |
| Acute Gene Regulation: High Frequency | Acute Gene Regulation: NR4A3 mRNA Expression Pre and Post-Stimulation | Pre-Stimulation | 2.711 arbitrary units | Standard Deviation 0.49 |
| Acute Gene Regulation: High Frequency | Acute Gene Regulation: NR4A3 mRNA Expression Pre and Post-Stimulation | Post-Stimulation | 5.772 arbitrary units | Standard Deviation 0.49 |
p-value: <0.001ANOVA
p-value: <0.001ANOVA
Primary
Acute Gene Regulation: PDK4 mRNA Expression Pre and Post-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.
Time frame: 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
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Acute Gene Regulation: Low Frequency | Acute Gene Regulation: PDK4 mRNA Expression Pre and Post-Stimulation | Pre-Stimulation | 6.64 arbitrary units | Standard Deviation 0.38 |
| Acute Gene Regulation: Low Frequency | Acute Gene Regulation: PDK4 mRNA Expression Pre and Post-Stimulation | Post-Stimulation | 7.23 arbitrary units | Standard Deviation 0.38 |
| Acute Gene Regulation: High Frequency | Acute Gene Regulation: PDK4 mRNA Expression Pre and Post-Stimulation | Pre-Stimulation | 6.46 arbitrary units | Standard Deviation 0.44 |
| Acute Gene Regulation: High Frequency | Acute Gene Regulation: PDK4 mRNA Expression Pre and Post-Stimulation | Post-Stimulation | 7.45 arbitrary units | Standard Deviation 0.44 |
p-value: 0.148ANOVA
p-value: 0.005ANOVA
Primary
Acute Gene Regulation: PGC1-alpha mRNA Expression Pre and Post-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.
Time frame: 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
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Acute Gene Regulation: Low Frequency | Acute Gene Regulation: PGC1-alpha mRNA Expression Pre and Post-Stimulation | Pre-Stimulation | 5.37 arbitrary units | Standard Deviation 0.48 |
| Acute Gene Regulation: Low Frequency | Acute Gene Regulation: PGC1-alpha mRNA Expression Pre and Post-Stimulation | Post-Stimulation | 6.72 arbitrary units | Standard Deviation 0.39 |
| Acute Gene Regulation: High Frequency | Acute Gene Regulation: PGC1-alpha mRNA Expression Pre and Post-Stimulation | Pre-Stimulation | 4.92 arbitrary units | Standard Deviation 0.3 |
| Acute Gene Regulation: High Frequency | Acute Gene Regulation: PGC1-alpha mRNA Expression Pre and Post-Stimulation | Post-Stimulation | 6.43 arbitrary units | Standard Deviation 0.3 |
p-value: <0.001ANOVA
p-value: <0.001ANOVA
Primary
Post-training Gene Regulation: ACTN3 mRNA Expression Baseline and Post-Training
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.
Time frame: 6 months
Population: This outcome measure only pertains to the Training study arms: Training Study: Low Frequency and Training Study: High Frequency.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Acute Gene Regulation: Low Frequency | Post-training Gene Regulation: ACTN3 mRNA Expression Baseline and Post-Training | Baseline | 8.95 arbitrary units | Standard Deviation 0.79 |
| Acute Gene Regulation: Low Frequency | Post-training Gene Regulation: ACTN3 mRNA Expression Baseline and Post-Training | Post-Training | 8.20 arbitrary units | Standard Deviation 0.71 |
| Acute Gene Regulation: High Frequency | Post-training Gene Regulation: ACTN3 mRNA Expression Baseline and Post-Training | Baseline | 8.51 arbitrary units | Standard Deviation 0.74 |
| Acute Gene Regulation: High Frequency | Post-training Gene Regulation: ACTN3 mRNA Expression Baseline and Post-Training | Post-Training | 7.12 arbitrary units | Standard Deviation 0.74 |
p-value: 0.01ANOVA
p-value: 0.001ANOVA
Primary
Post-training Gene Regulation: MYH6 mRNA Expression Baseline and Post-Training
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.
Time frame: 6 months
Population: This outcome measure only pertains to the Training study arms: Training Study: Low Frequency and Training Study: High Frequency.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Acute Gene Regulation: Low Frequency | Post-training Gene Regulation: MYH6 mRNA Expression Baseline and Post-Training | Baseline | 6.61 arbitrary units | Standard Deviation 0.71 |
| Acute Gene Regulation: Low Frequency | Post-training Gene Regulation: MYH6 mRNA Expression Baseline and Post-Training | Post-Training | 7.10 arbitrary units | Standard Deviation 0.88 |
| Acute Gene Regulation: High Frequency | Post-training Gene Regulation: MYH6 mRNA Expression Baseline and Post-Training | Baseline | 5.38 arbitrary units | Standard Deviation 0.69 |
| Acute Gene Regulation: High Frequency | Post-training Gene Regulation: MYH6 mRNA Expression Baseline and Post-Training | Post-Training | 6.58 arbitrary units | Standard Deviation 0.69 |
p-value: 0.069ANOVA
p-value: 0.003ANOVA
Primary
Post-training Gene Regulation: MYH7 mRNA Expression Baseline and Post-Training
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.
Time frame: 6 months
Population: This outcome measure only pertains to the Training study arms: Training Study: Low Frequency and Training Study: High Frequency.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Acute Gene Regulation: Low Frequency | Post-training Gene Regulation: MYH7 mRNA Expression Baseline and Post-Training | Baseline | 8.55 arbitrary units | Standard Deviation 1.1 |
| Acute Gene Regulation: Low Frequency | Post-training Gene Regulation: MYH7 mRNA Expression Baseline and Post-Training | Post-Training | 9.43 arbitrary units | Standard Deviation 1.4 |
| Acute Gene Regulation: High Frequency | Post-training Gene Regulation: MYH7 mRNA Expression Baseline and Post-Training | Baseline | 7.16 arbitrary units | Standard Deviation 0.88 |
| Acute Gene Regulation: High Frequency | Post-training Gene Regulation: MYH7 mRNA Expression Baseline and Post-Training | Post-Training | 8.85 arbitrary units | Standard Deviation 0.88 |
p-value: 0.059ANOVA
p-value: 0.015ANOVA
Primary
Post-training Gene Regulation: MYL3 mRNA Expression Baseline and Post-Training
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.
Time frame: 6 months
Population: This outcome measure only pertains to the Training study arms: Training Study: Low Frequency and Training Study: High Frequency.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Acute Gene Regulation: Low Frequency | Post-training Gene Regulation: MYL3 mRNA Expression Baseline and Post-Training | Baseline | 7.37 arbitrary units | Standard Deviation 0.87 |
| Acute Gene Regulation: Low Frequency | Post-training Gene Regulation: MYL3 mRNA Expression Baseline and Post-Training | Post-Training | 8.01 arbitrary units | Standard Deviation 1.08 |
| Acute Gene Regulation: High Frequency | Post-training Gene Regulation: MYL3 mRNA Expression Baseline and Post-Training | Baseline | 6.38 arbitrary units | Standard Deviation 0.81 |
| Acute Gene Regulation: High Frequency | Post-training Gene Regulation: MYL3 mRNA Expression Baseline and Post-Training | Post-Training | 7.96 arbitrary units | Standard Deviation 0.81 |
p-value: 0.118ANOVA
p-value: 0.01ANOVA
Primary
Post-training Metabolism: C-reactive Protein (CRP)
Pre- and post-training C-reactive protein (CRP), measured via venipuncture and standard laboratory assays
Time frame: 6 months
Population: This outcome measure only pertains to the Training Study: Low Frequency arm. 11 participants contributed venous blood samples.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Acute Gene Regulation: Low Frequency | Post-training Metabolism: C-reactive Protein (CRP) | Pre-training | 11.427 mg/L | Standard Deviation 11.137 |
| Acute Gene Regulation: Low Frequency | Post-training Metabolism: C-reactive Protein (CRP) | Post-training | 4.545 mg/L | Standard Deviation 2.581 |
p-value: 0.04t-test, 2 sided
Primary
Post-training Metabolism: Fasting Glucose
Pre- and post-training fasting glucose, measured via venipuncture and standard laboratory assays
Time frame: 6 months
Population: This outcome measure only pertains to the Training Study: Low Frequency arm. 11 participants contributed venous blood samples.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Acute Gene Regulation: Low Frequency | Post-training Metabolism: Fasting Glucose | Pre-Training | 94.727 mg/dL | Standard Deviation 10.725 |
| Acute Gene Regulation: Low Frequency | Post-training Metabolism: Fasting Glucose | Post-Training | 91.091 mg/dL | Standard Deviation 14.223 |
p-value: 0.345t-test, 2 sided
Primary
Post-training Metabolism: Fasting Glucose-insulin Ratio
Pre- and post-training ratio of fasting glucose to fasting insulin, measured via venipuncture and standard laboratory assays
Time frame: 6 months
Population: This outcome measure only pertains to the Training Study: Low Frequency arm. 11 participants contributed venous blood samples.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Acute Gene Regulation: Low Frequency | Post-training Metabolism: Fasting Glucose-insulin Ratio | Pre-Training | 8.649 ratio | Standard Deviation 5.573 |
| Acute Gene Regulation: Low Frequency | Post-training Metabolism: Fasting Glucose-insulin Ratio | Post-Training | 11.274 ratio | Standard Deviation 5.417 |
p-value: 0.264t-test, 2 sided
Primary
Post-training Metabolism: Fasting Hemoglobin A1c (HBA1c)
Pre- and post-training fasting Hemoglobin A1C (HbA1c), measured via venipuncture and standard laboratory assays
Time frame: 6 months
Population: This outcome measure only pertains to the Training Study: Low Frequency arm. 11 participants contributed venous blood samples.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Acute Gene Regulation: Low Frequency | Post-training Metabolism: Fasting Hemoglobin A1c (HBA1c) | Pre-training | 4.227 percent of total hemoglobin | Standard Deviation 1.03 |
| Acute Gene Regulation: Low Frequency | Post-training Metabolism: Fasting Hemoglobin A1c (HBA1c) | Post-training | 3.970 percent of total hemoglobin | Standard Deviation 0.946 |
p-value: 0.266t-test, 2 sided
Primary
Post-training Metabolism: Fasting Insulin
Pre- and post-training fasting insulin, measured via venipuncture and standard laboratory assays
Time frame: 6 months
Population: This outcome measure only pertains to the Training Study: Low Frequency arm. 11 participants contributed venous blood samples.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Acute Gene Regulation: Low Frequency | Post-training Metabolism: Fasting Insulin | Pre-Training | 19.245 microU/mL | Standard Deviation 16.387 |
| Acute Gene Regulation: Low Frequency | Post-training Metabolism: Fasting Insulin | Post-Training | 8.305 microU/mL | Standard Deviation 3.407 |
p-value: 0.036t-test, 2 sided
Primary
Post-training Subject-report Measures: PROMIS Mental Health
Pre- and post-training Patient Reported Outcomes Measurement Information Systems (PROMIS) Global Health - Mental health T-score Theoretical minimum = 21.2, Theoretical maximum = 67.6, higher scores signify more of the construct being measured (eg. mental health). US population mean = 50, SD = 10.
Time frame: 6 months
Population: This outcome measure pertained only to the Training Study: Low Frequency arm. 11 participants contributed PROMIS subject-report measures.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Acute Gene Regulation: Low Frequency | Post-training Subject-report Measures: PROMIS Mental Health | Pre-training | 47.0 T-score | Standard Deviation 5.1 |
| Acute Gene Regulation: Low Frequency | Post-training Subject-report Measures: PROMIS Mental Health | Post-training | 47.3 T-score | Standard Deviation 5.1 |
p-value: 0.858t-test, 2 sided
Primary
Post-training Subject-report Measures: PROMIS Physical Health
Pre- and post-training Patient Reported Outcomes Measurement Information Systems (PROMIS) Global Health - Physical health T-score Theoretical minimum = 16.2, Theoretical maximum = 67.7, higher scores signify more of the construct being measured (eg. physical health). US population mean = 50, SD = 10.
Time frame: 6 months
Population: This outcome measure pertained only to the Training Study: Low Frequency arm. 11 participants contributed PROMIS subject-report measures.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Acute Gene Regulation: Low Frequency | Post-training Subject-report Measures: PROMIS Physical Health | Pre-training | 39.9 T-score | Standard Deviation 4.9 |
| Acute Gene Regulation: Low Frequency | Post-training Subject-report Measures: PROMIS Physical Health | Post-training | 39.5 T-score | Standard Deviation 5.6 |
p-value: 0.573t-test, 2 sided
Primary
Pre-training Subject Report Measures: PROMIS Mental Health
Pre-training Patient Reported Outcomes Measurement Information Systems (PROMIS) Global Health - Mental health T-score Theoretical minimum = 21.2, Theoretical maximum = 67.6, higher scores signify more of the construct being measured (eg. mental health). US population mean = 50, SD = 10.
Time frame: Baseline
Population: This outcome measure pertained only to the Training Study: Low Frequency arm and to the Comparator Cohort. 11 participants in the Training study: low frequency arm contributed PROMIS subject-report measures.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Acute Gene Regulation: Low Frequency | Pre-training Subject Report Measures: PROMIS Mental Health | 47.0 T-score | Standard Deviation 5.1 |
| Acute Gene Regulation: High Frequency | Pre-training Subject Report Measures: PROMIS Mental Health | 47.3 T-score | Standard Deviation 4.1 |
p-value: 0.895t-test, 2 sided
Primary
Pre-training Subject-report Measures: PROMIS Physical Health
Pre-training Patient Reported Outcomes Measurement Information Systems (PROMIS) Global Health - Physical health T-score Theoretical minimum = 16.2, Theoretical maximum = 67.7, higher scores signify more of the construct being measured (eg. physical health). US population mean = 50, SD = 10.
Time frame: Baseline
Population: This outcome measure pertained only to the Training Study: Low Frequency arm and to the Comparator Cohort. 11 participants in the Training study: low frequency arm contributed PROMIS subject-report measures.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Acute Gene Regulation: Low Frequency | Pre-training Subject-report Measures: PROMIS Physical Health | 39.9 T-score | Standard Deviation 4.9 |
| Acute Gene Regulation: High Frequency | Pre-training Subject-report Measures: PROMIS Physical Health | 37.0 T-score | Standard Deviation 4.1 |
p-value: 0.109t-test, 2 sided