Spinal Cord InjuriesNCT01093014
Novel Intervention to Influence Muscle Plasticity in Veterans
A study testing Low-force muscle stimulation, High-force muscle stimulation and Sequential low-force and high-force muscle stimulation in people with Spinal Cord Injuries, run by VA Office of Research and Development at 1 site in United States.
Trial summary
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. Read more about this study
- Who is it for?
- Ages 18 to 75 years
- Conditions the study is for
- Spinal Cord Injuries
- What is being tested?
- Low-force muscle stimulation, High-force muscle stimulation and Sequential low-force and high-force muscle stimulation
- Type of treatment
- Lifestyle or therapy programme
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 33 participants
- Where
- 1 siteUnited States
- Study dates
- Apr 2011to Dec 2014
- 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 to 75 years
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- Inclusion criteria for all subjects will be upper motor neuron lesions between the 10th thoracic and the 7th cervical spinal levels. The completeness of the injury will be verified by somatosensory evoked potentials.
Who cannot join
- Subjects will be excluded if they have pressure ulcers
- chronic infection
- lower extremity muscle contractures
- deep vein thrombosis
- recent limb fractures
- muscle metabolic disorders
Show all 9Show fewer
- any comorbid disease known to affect bone metabolism (such as parathyroid dysfunction)
- or if they are pregnant or plan to become pregnant.
- Subjects with distal femur trabecular bone mineral density less than 50 mg/cm3 will be excluded from participation in quadriceps electrical stimulation training
Trial locations and contacts
1 site in 1 country.
United States1 site
Iowa City VA Health Care System, Iowa City, IA
Iowa City, Iowa, 52246-2208
About this study
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.
Read the detailed description
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.
- Conditions
- Spinal Cord Injuries
- Being tested
- Low-force muscle stimulation, High-force muscle stimulation, Sequential low-force and high-force muscle stimulation
- Keywords
- Quadriceps Muscle, RNA, Messenger, Hypertrophy, Electric Stimulation Therapy
- Medical subject headings
- Spinal Cord Injuries, Hypertrophy
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Low-force muscle stimulationBehavioural
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.
High-force muscle stimulationBehavioural
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 stimulationBehavioural
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.
| Study group | Role | What they receive |
|---|---|---|
| Arm 1: High-force muscle stimulation | Experimental | High-force muscle stimulation Receives: Behavioral: High-force muscle stimulation |
| Arm 2: Low-force muscle stimulation | Experimental | Low-force muscle stimulation Receives: Behavioral: Low-force muscle stimulation |
| Arm 3: Sequential low-force and high-force muscle stimulation | Experimental | Sequential low-force and high-force muscle stimulation Receives: Behavioral: Sequential low-force and high-force muscle stimulation |
What is being measured
The primary outcome is the main question the study is designed to answer.
HF Muscle Force
Muscle force evoked during high-force muscle stimulation
Measured: up to 1 year
LF Muscle Force
Muscle force evoked during low-force muscle stimulation
Measured: 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.
Measured: 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.
Measured: up to 1 year
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted25 Mar 2010 (estimated)
- Study startApr 2011
- Primary completionDec 2014
- Study completionDec 2014
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 (8)Papers the sponsor has linked to this study.
- Other trials for Spinal Cord InjuriesStudies of the same condition, open and under way.
- More trials run by VA Office of Research and DevelopmentThe sponsor's other registered studies.
- 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
- Treatment
- Allocation
- Non-randomised
- Intervention model
- Single group
- Masking
- None (open label)
- Enrolment
- 33 participants (actual)
Sponsor and investigators
- Lead sponsor
- VA Office of Research and Development
- Sponsor type
- US federal agency
- Collaborators
- University of Iowa
- Responsible party
- Sponsor
- Investigators
- Richard K Shields, PhD PT, Principal investigator, Iowa City VA Health Care System, Iowa City, IA
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT01093014
- Sponsor's protocol ID
- B7097-R
- Status last verified
- Feb 2016
- First submitted
- 23 Mar 2010
- Last updated
- 10 Mar 2016
- Results posted
- Yes, on ClinicalTrials.gov
- Data monitoring committee
- No
- Individual data sharing
- No
Publications
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.
PubMed 21171097Kunkel 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, 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 22507023Dudley-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.
PubMed 23408218Dudley-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 22187008Petrie 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 24744911Petrie 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 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 25635001
Study at a glance
From the registry record, last updated by the sponsor on 10 Mar 2016. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Novel Intervention to Influence Muscle Plasticity in Veterans
- ClinicalTrials.gov ID
- NCT01093014
- Acronym / sponsor ID
- B7097-R
- Conditions
- Spinal Cord Injuries
- Keywords
- Quadriceps Muscle, RNA, Messenger, Hypertrophy, Electric Stimulation Therapy
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 33 participants (actual)
- Lead sponsor
- VA Office of Research and DevelopmentUS federal agency
- Collaborators
- University of Iowa
- Study start
- Apr 2011
- Primary completion
- Dec 2014 (actual)
- Study completion
- Dec 2014 (actual)
- First posted
- 25 Mar 2010 (estimated)
- Results
- Posted 5 Feb 2016
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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.
Detailed description
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.
Study design
- Primary purpose
- Treatment
- Allocation
- Non-randomised
- Intervention model
- Single group
- Masking
- None (open label)
- Number of arms
- 3
| Arm | Type | Receives |
|---|---|---|
| Arm 1: High-force muscle stimulation | Experimental | Behavioral: High-force muscle stimulationHigh-force muscle stimulation |
| Arm 2: Low-force muscle stimulation | Experimental | Behavioral: Low-force muscle stimulationLow-force muscle stimulation |
| Arm 3: Sequential low-force and high-force muscle stimulation | Experimental | Behavioral: Sequential low-force and high-force muscle stimulationSequential low-force and high-force muscle stimulation |
Who may qualify
- Ages
- 18 to 75 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (1 listed)
- Inclusion criteria for all subjects will be upper motor neuron lesions between the 10th thoracic and the 7th cervical spinal levels. The completeness of the injury will be verified by somatosensory evoked potentials.
Key exclusion criteria (9 listed)
- Subjects will be excluded if they have pressure ulcers
- chronic infection
- lower extremity muscle contractures
- deep vein thrombosis
- recent limb fractures
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-force muscle stimulationElectrical 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. | Behavioural | Arm 2: Low-force muscle stimulation |
| High-force muscle stimulationElectrical 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. | Behavioural | Arm 1: High-force muscle stimulation |
| Sequential low-force and high-force muscle stimulationElectrical 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. | Behavioural | Arm 3: Sequential low-force and high-force muscle stimulation |
Primary outcome
HF Muscle Force
Time frame: up to 1 year
Muscle force evoked during high-force muscle stimulation
LF Muscle Force
Time frame: up to 1 year
Muscle force evoked during low-force muscle stimulation
Skeletal Muscle Gene Regulation: MSTN
Time frame: up to 1 year
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.
Skeletal Muscle Gene Expression: PPARGC1A
Time frame: up to 1 year
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.
Results and safety
Loading the posted results from ClinicalTrials.gov…
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 10 Mar 2016.
- Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
- 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 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 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 23408218Dudley-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.
- Results publication: 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.
- Results publication: 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.
- Results publication: 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.
- Results publication: PubMed 25635001Petrie 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.
- 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
Iowa City VA Health Care System, Iowa City, IA
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-force muscle stimulation, High-force muscle stimulation and Sequential low-force and high-force muscle stimulation in people with Spinal Cord Injuries, run by VA Office of Research and Development 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 9 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 10 Mar 2016. 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 5 Feb 2016). 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?
HF Muscle Force (time frame: up to 1 year). The study lists 4 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 NCT01093014, which also lists 8 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 10 Mar 2016.