Not provided
Not provided
Not provided
Not provided
Not provided
Not provided
Not provided
Not provided
Not provided
Not provided
| Name | Class |
|---|---|
| University of Iowa | OTHER |
Not provided
Not provided
Not provided
Not provided
Not provided
Not provided
The loss of muscle contraction (paralysis) removes an important stimulus for maintenance of overall health for individuals with complete spinal cord injury (SCI). Increased protein catabolism (atrophy) limits important stresses to the skeletal system. Bone loss doubles the risk of fracture and contributes to increased mortality in Veterans with SCI. Metabolic syndrome and diabetes lead to heart disease in Veterans with SCI at higher rates than the general population. Exercise methods to sustain muscle tissue, bone density, and metabolic stability after SCI are lacking scientific justification. If left unchecked, the secondary complications of SCI can be health limiting or even life threatening to Veterans with paralysis. The importance of maintaining the health of the musculoskeletal system after SCI has never been greater as a cure for paralysis may become a reality. Contemporary rehabilitation interventions lack the ability to functionally load muscle tissue, quantify the dose of load, stress the cardiovascular system, monitor the overall stresses during daily exercise training, or offer portability to improve compliance with the exercise. The long-term goal of this project is to establish the optimal dose of muscle and bone stress during functional exercise in order to improve the health of Veterans with complete paralysis. The practical outcome of this research is to offer a form of activity that is feasible, portable, and grounded in sound scientific principles. The scientific goal is to understand whether the dose of force generated in paralyzed muscle via evoked contractions is critical to muscle atrophy/hypertrophy molecular pathways, physiologic performance, and insulin sensitivity. The investigators will administer various doses of muscle force by manipulating the frequency of electrical stimulation while keeping stimulation current (i.e. muscle fiber recruitment) constant. Interestingly, no previous study has examined the dose of muscle force necessary to trigger adaptations in protein synthesis/degradation pathways. The investigators wish to discover the most effective method to maintain the molecular and physiologic properties of paralyzed muscle. The investigators believe such a method will be in urgent demand as a co-intervention with pharmaceutical strategies in post-SCI rehabilitation.
Central Hypothesis: The investigators hypothesize that high muscle force induced via a novel, portable, active standing intervention will increase muscle force properties, alter gene expression for atrophy and fiber type pathways, and improve systemic insulin sensitivity in Veterans with complete paralysis.
Aim 1: To determine the training effects of 3 tiers of quadriceps muscle force on muscle physiological properties in Veterans with chronic paralysis from SCI.
Aim 2: To determine the training effects of 3 tiers of quadriceps muscle forces on muscle mRNA for genes associated with atrophy and muscle fiber type in Veterans with complete paralysis.
Aim 3: To determine the training effects of 2 tiers of compressive load induced by quadriceps muscle forces on insulin sensitivity and markers of inflammation in Veterans with SCI.
Not provided
Not provided
Not provided
Not provided
| Label | Type | Description | Intervention Names |
|---|---|---|---|
| Arm 1: High-force muscle stimulation | Experimental | High-force muscle stimulation |
|
| Arm 2: Low-force muscle stimulation | Experimental | Low-force muscle stimulation |
|
| Arm 3: Sequential low-force and high-force muscle stimulation | Experimental | Sequential low-force and high-force muscle stimulation |
|
| Name | Type | Description | Arm Group Labels | Other Names |
|---|---|---|---|---|
| Low-force muscle stimulation | Behavioral | Electrical stimulation of paralyzed muscle in seated or standing to evoke non-summated, low-force contractions, using either a lab-based system or a portable system for up to 1 year. |
| Measure | Description | Time Frame |
|---|---|---|
| HF Muscle Force | Muscle force evoked during high-force muscle stimulation | up to 1 year |
| LF Muscle Force | Muscle force evoked during low-force muscle stimulation | up to 1 year |
| Skeletal Muscle Gene Regulation: MSTN | Messenger ribonucleic acid (mRNA) expression fold-change for myostatin (MSTN). Fold change: post-intervention expression / pre-intervention expression. Values greater than 1.0 indicate up-regulation. Values less than 1.0 indicate down-regulation. | up to 1 year |
| Skeletal Muscle Gene Expression: PPARGC1A | Messenger ribonucleic acid (mRNA) expression fold-change for peroxisome proliferator-activated receptor gamma, coactivator 1 alpha (PPARGC1A). Fold change: post-intervention expression / pre-intervention expression. Values greater than 1.0 indicate up-regulation. Values less than 1.0 indicate down-regulation. | up to 1 year |
Not provided
Not provided
Inclusion Criteria:
Exclusion Criteria:
Not provided
Not provided
Not provided
Not provided
Not provided
| Name | Affiliation | Role |
|---|---|---|
| Richard K Shields, PhD PT | Iowa City VA Health Care System, Iowa City, IA | Principal Investigator |
| Facility | Status | City | State | ZIP | Country | Contacts |
|---|---|---|---|---|---|---|
| Iowa City VA Health Care System, Iowa City, IA | Iowa City | Iowa | 52246-2208 | United States |
| PubMed Identifier | Type | Citation | Retractions |
|---|---|---|---|
| 21171097 | Background | Adams 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. | |
| 21641545 | Background | Kunkel 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. |
Not provided
Not provided
Not provided
Not provided
Not provided
Not provided
Not provided
Not provided
Not provided
Not provided
| ID | Title | Description |
|---|---|---|
| FG000 | Arm 1: High-force Muscle Stimulation | High-force muscle stimulation |
| FG001 | Arm 2: Low-force Muscle Stimulation | Low-force muscle stimulation |
| FG002 | Arm 3: Sequential Low-force and High-force Muscle Stimulation | Sequential low-force and high-force muscle stimulation |
| Title | Milestones | Reasons Not Completed | ||||||||||||
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Overall Study |
|
Not provided
Not provided
| ID | Title | Description |
|---|---|---|
| BG000 | Arm 1: High-force Muscle Stimulation | High-force muscle stimulation |
| BG001 | Arm 2: Low-force Muscle Stimulation | Low-force muscle stimulation |
| Units | Counts |
|---|---|
| Participants |
|
| Title | Description | Population Description | Parameter Type | Dispersion Type | Unit of Measure | Calculate Percentage | Denominator Units Selected | Denominators | Classes |
|---|---|---|---|---|---|---|---|---|---|
| Age, Continuous | Mean |
| Type | Title | Description | Population Description | Reporting Status | Anticipated Posting Date | Parameter Type | Dispersion Type | Unit of Measure | Calculate Percentage | Time Frame | Units Analyzed | Denominator Units Selected | Arm/Group Information | Denominators | Classes | Analyses | ||||||
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Primary | HF Muscle Force | Muscle force evoked during high-force muscle stimulation | Posted | Mean | Standard Deviation | Newtons (N) | up to 1 year |
|
Up to 1 year
Not provided
Not provided
| ID | Title | Description | Deaths (Affected) | Deaths (At Risk) | Serious Events (Affected) | Serious Events (At Risk) | Other Events (Affected) | Other Events (At Risk) |
|---|---|---|---|---|---|---|---|---|
| EG000 | Arm 1: High-force Muscle Stimulation | High-force muscle stimulation |
Not provided
Not provided
Not provided
| Title | Organization | Phone | Extension | |
|---|---|---|---|---|
| Richard K. Shields PhD, PT | University of Iowa / Iowa City VA Medical Center | 319-335-9791 | richard-shields@uiowa.edu |
Not provided
| ID | Term |
|---|---|
| D013119 | Spinal Cord Injuries |
| D006984 | Hypertrophy |
| ID | Term |
|---|---|
| D013118 | Spinal Cord Diseases |
| D002493 | Central Nervous System Diseases |
| D009422 | Nervous System Diseases |
| D020196 | Trauma, Nervous System |
Not provided
Not provided
Not provided
Not provided
Not provided
Not provided
Not provided
| High-force muscle stimulation | Behavioral | Electrical stimulation of paralyzed muscle in seated or standing to evoke summated, high-force contractions, using either a lab-based system or a portable system for up to 1 year. |
|
| Sequential low-force and high-force muscle stimulation | Behavioral | Electrical stimulation of paralyzed muscle in seated or standing to evoke non-summated, low-force contractions, followed by: 1) a 1-month washout period, then; 2) electrical stimulation to evoke summated, high-force contractions. |
|
| 22507023 | Background | McHenry 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. |
| 23408218 | Background | Dudley-Javoroski S, Shields RK. Regional cortical and trabecular bone loss after spinal cord injury. J Rehabil Res Dev. 2012;49(9):1365-76. doi: 10.1682/jrrd.2011.12.0245. |
| 22187008 | Result | 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. |
| 24744911 | Result | Petrie 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. |
| 25531450 | Result | Petrie 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. |
| 25635001 | Result | Petrie 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. |
| BG002 | Arm 3: Sequential Low-force and High-force Muscle Stimulation | Sequential low-force and high-force muscle stimulation |
| BG003 | Total | Total of all reporting groups |
| years |
|
| Sex: Female, Male | Count of Participants | Participants |
|
| OG002 |
| Arm 3: Sequential Low-force and High-force Muscle Stimulation |
Sequential low-force and high-force muscle stimulation: Electrical stimulation of paralyzed muscle to evoke non-summated, low-force contractions, followed by: 1) a 1-month washout period, then; 2) electrical stimulation to evoke summated, high-force contractions. |
|
|
| Primary | LF Muscle Force | Muscle force evoked during low-force muscle stimulation | Posted | Mean | Standard Deviation | N (newtons) | up to 1 year |
|
|
|
| Primary | Skeletal Muscle Gene Regulation: MSTN | Messenger ribonucleic acid (mRNA) expression fold-change for myostatin (MSTN). Fold change: post-intervention expression / pre-intervention expression. Values greater than 1.0 indicate up-regulation. Values less than 1.0 indicate down-regulation. | Only a subset of Arm 1 and Arm 3 participants underwent biopsy: we achieved statistical power with these subsets and further biopsies were not warranted. | Posted | Mean | Standard Deviation | fold-change | up to 1 year |
|
|
|
| Primary | Skeletal Muscle Gene Expression: PPARGC1A | Messenger ribonucleic acid (mRNA) expression fold-change for peroxisome proliferator-activated receptor gamma, coactivator 1 alpha (PPARGC1A). Fold change: post-intervention expression / pre-intervention expression. Values greater than 1.0 indicate up-regulation. Values less than 1.0 indicate down-regulation. | Only a subset of Arm 1 and Arm 3 participants underwent biopsy: we achieved statistical power with these subsets and further biopsies were not warranted. | Posted | Mean | Standard Deviation | fold-change | up to 1 year |
|
|
|
| 0 |
| 12 |
| 0 |
| 12 |
| EG001 | Arm 2: Low-force Muscle Stimulation | Low-force muscle stimulation | 0 | 9 | 0 | 9 |
| EG002 | Arm 3: Sequential Low-force and High-force Muscle Stimulation | Sequential low-force and high-force muscle stimulation | 0 | 12 | 0 | 12 |
Not provided
Not provided
Not provided
| D014947 | Wounds and Injuries |
| D020763 | Pathological Conditions, Anatomical |
| D013568 | Pathological Conditions, Signs and Symptoms |