Spinal Cord InjuriesNCT03139344
Long Duration Activity and Metabolic Control After Spinal Cord Injury
A study testing Low-frequency Exercise and High-frequency Exercise in people with Spinal Cord Injuries, run by Richard K Shields at 1 site in United States.
Trial 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. Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Spinal Cord Injuries
- What is being tested?
- Low-frequency Exercise and High-frequency Exercise
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 89 participants
- Where
- 1 siteUnited States
- Study dates
- 1 Aug 2015to 1 Apr 2022
- Phase
- Interventional
- Are there results?
- Yes, posted in the registrySummary in the doctors' view
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 years and older
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- Motor complete SCI (AIS A-B)
Who cannot join
- Pressure ulcers, chronic infection, lower extremity muscle contractures, deep vein thrombosis, bleeding disorder, recent limb fractures, pregnancy, metformin or other medications for diabetes
Trial locations and contacts
1 site in 1 country.
About this study
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.
Read the 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.
- Conditions
- Spinal Cord Injuries
- Being tested
- Low-frequency Exercise, High-frequency Exercise
- Keywords
- metabolism, exercise, glucose, secondary health conditions, quality of life
- Medical subject headings
- Spinal Cord Injuries, Motor Activity
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Low-frequency ExerciseOther
The quadriceps/hamstrings will perform exercise via the application of low-frequency electrical stimulation.
High-frequency ExerciseOther
The quadriceps/hamstrings will perform exercise via the application of high-frequency electrical stimulation.
| Study group | Role | What they receive |
|---|---|---|
| Acute gene regulation: low frequency | Experimental | Adaptations in gene regulation in response to single-session low-frequency exercise. Receives: Other: Low-frequency Exercise |
| Acute gene regulation: high frequency | Experimental | Adaptations in gene regulation in response to single-session high-frequency exercise. Receives: Other: High-frequency Exercise |
| Training study: low frequency | Experimental | Adaptations in gene regulation, systemic metabolic markers, and patient-report metrics in response to training with low-frequency exercise. Receives: Other: Low-frequency Exercise |
| Training study: high frequency | Experimental | Adaptations in gene regulation in response to training with high-frequency exercise. Receives: Other: High-frequency Exercise |
| Comparator cohort | No intervention | Participants will undergo selected outcome measures to provide comparison values for Experimental arms. |
What is being measured
The primary outcome is the main question the study is designed to answer.
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.
Measured: 3 hours after a single session of electrical stimulation
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.
Measured: 3 hours after a single session of electrical stimulation
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.
Measured: 3 hours after a single session of electrical stimulation
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.
Measured: 3 hours after a single session of electrical stimulation
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.
Measured: 6 months
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.
Measured: 6 months
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.
Measured: 6 months
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.
Measured: 6 months
Post-training Metabolism: Fasting Insulin
Pre- and post-training fasting insulin, measured via venipuncture and standard laboratory assays
Measured: 6 months
Post-training Metabolism: Fasting Glucose
Pre- and post-training fasting glucose, measured via venipuncture and standard laboratory assays
Measured: 6 months
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
Measured: 6 months
Post-training Metabolism: Fasting Hemoglobin A1c (HBA1c)
Pre- and post-training fasting Hemoglobin A1C (HbA1c), measured via venipuncture and standard laboratory assays
Measured: 6 months
Post-training Metabolism: C-reactive Protein (CRP)
Pre- and post-training C-reactive protein (CRP), measured via venipuncture and standard laboratory assays
Measured: 6 months
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.
Measured: Baseline
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.
Measured: Baseline
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.
Measured: 6 months
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.
Measured: 6 months
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted3 May 2017
- Study start1 Aug 2015
- Primary completion1 Apr 2022
- Study completion1 Apr 2022
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Posted resultsParticipant flow, outcome measures and adverse events reported by the sponsor.
- Publications (28)Papers the sponsor has linked to this study.
- Other trials for Spinal Cord InjuriesStudies of the same condition, open and under way.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase N/A
- Primary purpose
- Basic science
- Allocation
- Non-randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Enrolment
- 89 participants (actual)
Sponsor and investigators
- Lead sponsor
- Richard K Shields
- Sponsor type
- University, hospital or other
- Collaborators
- Eunice Kennedy Shriver National Institute of Child Health and Human Development (NICHD)
- Responsible party
- Sponsor-investigator, Richard K Shields, University of Iowa
- Investigators
- Richard K Shields, PhD, PT, Principal investigator, University of Iowa
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT03139344
- Sponsor's protocol ID
- 201503732
- Other IDs
- R01HD082109
- Status last verified
- Jan 2023
- First submitted
- 28 Apr 2017
- Last updated
- 16 Feb 2023
- Results posted
- Yes, on ClinicalTrials.gov
- Data monitoring committee
- No
- FDA-regulated drug
- No
- FDA-regulated device
- No
- Individual data sharing
- No
Publications
Dudley-Javoroski S, Saha PK, Liang G, Li C, Gao Z, Shields RK. High dose compressive loads attenuate bone mineral loss in humans with spinal cord injury. Osteoporos Int. 2012 Sep;23(9):2335-46. doi: 10.1007/s00198-011-1879-4. Epub 2011 Dec 21.
PubMed 22187008Dudley-Javoroski S, Shields RK. Dose estimation and surveillance of mechanical loading interventions for bone loss after spinal cord injury. Phys Ther. 2008 Mar;88(3):387-96. doi: 10.2522/ptj.20070224. Epub 2008 Jan 17.
PubMed 18202080Dudley-Javoroski S, Shields RK. Active-resisted stance modulates regional bone mineral density in humans with spinal cord injury. J Spinal Cord Med. 2013 May;36(3):191-9. doi: 10.1179/2045772313Y.0000000092.
PubMed 23809588Dudley-Javoroski S, Littmann AE, Iguchi M, Shields RK. Doublet stimulation protocol to minimize musculoskeletal stress during paralyzed quadriceps muscle testing. J Appl Physiol (1985). 2008 Jun;104(6):1574-82. doi: 10.1152/japplphysiol.00892.2007. Epub 2008 Apr 24.
PubMed 18436697Dudley-Javoroski S, Shields RK. Assessment of physical function and secondary complications after complete spinal cord injury. Disabil Rehabil. 2006 Jan 30;28(2):103-10. doi: 10.1080/09638280500163828.
PubMed 16393840Adams CM, Suneja M, Dudley-Javoroski S, Shields RK. Altered mRNA expression after long-term soleus electrical stimulation training in humans with paralysis. Muscle Nerve. 2011 Jan;43(1):65-75. doi: 10.1002/mus.21831.
PubMed 21171097Frey Law LA, Shields RK. Femoral loads during passive, active, and active-resistive stance after spinal cord injury: a mathematical model. Clin Biomech (Bristol). 2004 Mar;19(3):313-21. doi: 10.1016/j.clinbiomech.2003.12.005.
PubMed 15003348Kunkel SD, Suneja M, Ebert SM, Bongers KS, Fox DK, Malmberg SE, Alipour F, Shields RK, Adams CM. mRNA expression signatures of human skeletal muscle atrophy identify a natural compound that increases muscle mass. Cell Metab. 2011 Jun 8;13(6):627-38. doi: 10.1016/j.cmet.2011.03.020.
PubMed 21641545McHenry CL, Wu J, Shields RK. Potential regenerative rehabilitation technology: implications of mechanical stimuli to tissue health. BMC Res Notes. 2014 Jun 3;7:334. doi: 10.1186/1756-0500-7-334.
PubMed 24894666McHenry CL, Shields RK. A biomechanical analysis of exercise in standing, supine, and seated positions: Implications for individuals with spinal cord injury. J Spinal Cord Med. 2012 May;35(3):140-7. doi: 10.1179/2045772312Y.0000000011.
PubMed 22507023Petrie MA, Suneja M, Faidley E, Shields RK. A minimal dose of electrically induced muscle activity regulates distinct gene signaling pathways in humans with spinal cord injury. PLoS One. 2014 Dec 22;9(12):e115791. doi: 10.1371/journal.pone.0115791. eCollection 2014.
PubMed 25531450Petrie MA, Suneja M, Faidley E, Shields RK. Low force contractions induce fatigue consistent with muscle mRNA expression in people with spinal cord injury. Physiol Rep. 2014 Feb 25;2(2):e00248. doi: 10.1002/phy2.248. eCollection 2014 Feb 1.
PubMed 24744911Shields RK, Dudley-Javoroski S. Monitoring standing wheelchair use after spinal cord injury: a case report. Disabil Rehabil. 2005 Feb 4;27(3):142-6. doi: 10.1080/09638280400009337.
PubMed 15823996Petrie M, Suneja M, Shields RK. Low-frequency stimulation regulates metabolic gene expression in paralyzed muscle. J Appl Physiol (1985). 2015 Mar 15;118(6):723-31. doi: 10.1152/japplphysiol.00628.2014. Epub 2015 Jan 29.
PubMed 25635001Zhorne R, Dudley-Javoroski S, Shields RK. Skeletal muscle activity and CNS neuro-plasticity. Neural Regen Res. 2016 Jan;11(1):69-70. doi: 10.4103/1673-5374.169623. No abstract available.
PubMed 26981083
Study at a glance
From the registry record, last updated by the sponsor on 16 Feb 2023. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Long Duration Activity and Metabolic Control After Spinal Cord Injury
- ClinicalTrials.gov ID
- NCT03139344
- Acronym / sponsor ID
- 201503732
- Conditions
- Spinal Cord Injuries
- Keywords
- metabolism, exercise, glucose, secondary health conditions, quality of life
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 89 participants (actual)
- Lead sponsor
- Richard K ShieldsUniversity, hospital or other
- Collaborators
- Eunice Kennedy Shriver National Institute of Child Health and Human Development (NICHD)
- Study start
- 1 Aug 2015 (actual)
- Primary completion
- 1 Apr 2022 (actual)
- Study completion
- 1 Apr 2022 (actual)
- First posted
- 3 May 2017 (actual)
- Results
- Posted 16 Feb 2023
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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.
Study design
- Primary purpose
- Basic science
- Allocation
- Non-randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Number of arms
- 5
| Arm | Type | Receives |
|---|---|---|
| Acute gene regulation: low frequency | Experimental | Other: Low-frequency ExerciseAdaptations in gene regulation in response to single-session low-frequency exercise. |
| Acute gene regulation: high frequency | Experimental | Other: High-frequency ExerciseAdaptations in gene regulation in response to single-session high-frequency exercise. |
| Training study: low frequency | Experimental | Other: Low-frequency ExerciseAdaptations in gene regulation, systemic metabolic markers, and patient-report metrics in response to training with low-frequency exercise. |
| Training study: high frequency | Experimental | Other: High-frequency ExerciseAdaptations in gene regulation in response to training with high-frequency exercise. |
| Comparator cohort | No intervention | –Participants will undergo selected outcome measures to provide comparison values for Experimental arms. |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (1 listed)
- Motor complete SCI (AIS A-B)
Key exclusion criteria (1 listed)
- Pressure ulcers, chronic infection, lower extremity muscle contractures, deep vein thrombosis, bleeding disorder, recent limb fractures, pregnancy, metformin or other medications for diabetes
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| Low-frequency ExerciseThe quadriceps/hamstrings will perform exercise via the application of low-frequency electrical stimulation. | Other | Acute gene regulation: low frequency, Training study: low frequency |
| High-frequency ExerciseThe quadriceps/hamstrings will perform exercise via the application of high-frequency electrical stimulation. | Other | Acute gene regulation: high frequency, Training study: high frequency |
Primary outcome
Acute Gene Regulation: NR4A3 mRNA Expression Pre and Post-Stimulation
Time frame: 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
Time frame: 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
Time frame: 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
Time frame: 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
Time frame: 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
Time frame: 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
Time frame: 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
Time frame: 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
Time frame: 6 months
Pre- and post-training fasting insulin, measured via venipuncture and standard laboratory assays
Post-training Metabolism: Fasting Glucose
Time frame: 6 months
Pre- and post-training fasting glucose, measured via venipuncture and standard laboratory assays
Post-training Metabolism: Fasting Glucose-insulin Ratio
Time frame: 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)
Time frame: 6 months
Pre- and post-training fasting Hemoglobin A1C (HbA1c), measured via venipuncture and standard laboratory assays
Post-training Metabolism: C-reactive Protein (CRP)
Time frame: 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
Time frame: 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
Time frame: 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
Time frame: 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
Time frame: 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.
Results and safety
Loading the posted results from ClinicalTrials.gov…
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 16 Feb 2023.
- Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
- Background: PubMed 22187008Dudley-Javoroski S, Saha PK, Liang G, Li C, Gao Z, Shields RK. High dose compressive loads attenuate bone mineral loss in humans with spinal cord injury. Osteoporos Int. 2012 Sep;23(9):2335-46. doi: 10.1007/s00198-011-1879-4. Epub 2011 Dec 21.
- Background: PubMed 18202080Dudley-Javoroski S, Shields RK. Dose estimation and surveillance of mechanical loading interventions for bone loss after spinal cord injury. Phys Ther. 2008 Mar;88(3):387-96. doi: 10.2522/ptj.20070224. Epub 2008 Jan 17.
- Background: PubMed 23809588Dudley-Javoroski S, Shields RK. Active-resisted stance modulates regional bone mineral density in humans with spinal cord injury. J Spinal Cord Med. 2013 May;36(3):191-9. doi: 10.1179/2045772313Y.0000000092.
- Background: PubMed 18436697Dudley-Javoroski S, Littmann AE, Iguchi M, Shields RK. Doublet stimulation protocol to minimize musculoskeletal stress during paralyzed quadriceps muscle testing. J Appl Physiol (1985). 2008 Jun;104(6):1574-82. doi: 10.1152/japplphysiol.00892.2007. Epub 2008 Apr 24.
- Background: PubMed 16393840Dudley-Javoroski S, Shields RK. Assessment of physical function and secondary complications after complete spinal cord injury. Disabil Rehabil. 2006 Jan 30;28(2):103-10. doi: 10.1080/09638280500163828.
- Background: PubMed 21171097Adams CM, Suneja M, Dudley-Javoroski S, Shields RK. Altered mRNA expression after long-term soleus electrical stimulation training in humans with paralysis. Muscle Nerve. 2011 Jan;43(1):65-75. doi: 10.1002/mus.21831.
- Background: PubMed 15003348Frey Law LA, Shields RK. Femoral loads during passive, active, and active-resistive stance after spinal cord injury: a mathematical model. Clin Biomech (Bristol). 2004 Mar;19(3):313-21. doi: 10.1016/j.clinbiomech.2003.12.005.
- Background: PubMed 21641545Kunkel SD, Suneja M, Ebert SM, Bongers KS, Fox DK, Malmberg SE, Alipour F, Shields RK, Adams CM. mRNA expression signatures of human skeletal muscle atrophy identify a natural compound that increases muscle mass. Cell Metab. 2011 Jun 8;13(6):627-38. doi: 10.1016/j.cmet.2011.03.020.
- Background: PubMed 24894666McHenry CL, Wu J, Shields RK. Potential regenerative rehabilitation technology: implications of mechanical stimuli to tissue health. BMC Res Notes. 2014 Jun 3;7:334. doi: 10.1186/1756-0500-7-334.
- Background: PubMed 22507023McHenry CL, Shields RK. A biomechanical analysis of exercise in standing, supine, and seated positions: Implications for individuals with spinal cord injury. J Spinal Cord Med. 2012 May;35(3):140-7. doi: 10.1179/2045772312Y.0000000011.
- Background: PubMed 25531450Petrie MA, Suneja M, Faidley E, Shields RK. A minimal dose of electrically induced muscle activity regulates distinct gene signaling pathways in humans with spinal cord injury. PLoS One. 2014 Dec 22;9(12):e115791. doi: 10.1371/journal.pone.0115791. eCollection 2014.
- Background: PubMed 24744911Petrie MA, Suneja M, Faidley E, Shields RK. Low force contractions induce fatigue consistent with muscle mRNA expression in people with spinal cord injury. Physiol Rep. 2014 Feb 25;2(2):e00248. doi: 10.1002/phy2.248. eCollection 2014 Feb 1.
- Individual participant dataSharing planned: No
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Richard K Shields, PhD, PT principal investigator
University of Iowa
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A study testing Low-frequency Exercise and High-frequency Exercise in people with Spinal Cord Injuries, run by Richard K Shields at 1 site in United States.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 1 inclusion and 1 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: finished, as of the sponsor's last update on 16 Feb 2023. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in United States. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
Are results available for this study?
Yes. Results are posted in the registry (first posted 16 Feb 2023). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Acute Gene Regulation: NR4A3 mRNA Expression Pre and Post-Stimulation (time frame: 3 hours after a single session of electrical stimulation). The study lists 17 primary outcomes in all. It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT03139344, which also lists 28 linked publications.
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 16 Feb 2023.