Novel Intervention to Influence Muscle Plasticity in Veterans

NCT ID: NCT01093014

Last Updated: 2016-03-10

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: NA
• Total Enrollment: 33 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2011-04-30
• Study Completion Date: 2014-12-31

Brief 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. 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.

Conditions

Spinal Cord Injuries

Study Design

• Allocation Method: NON_RANDOMIZED
• Intervention Model: SINGLE_GROUP
• Primary Study Purpose: TREATMENT
• Blinding Strategy: NONE

Study Groups

Arm 1: High-force muscle stimulation

High-force muscle stimulation

Group Type: EXPERIMENTAL

High-force muscle stimulation

Intervention Type: 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.

Arm 2: Low-force muscle stimulation

Low-force muscle stimulation

Group Type: EXPERIMENTAL

Low-force muscle stimulation

Intervention Type: 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.

Arm 3: Sequential low-force and high-force muscle stimulation

Sequential low-force and high-force muscle stimulation

Group Type: EXPERIMENTAL

Sequential low-force and high-force muscle stimulation

Intervention Type: 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.

Interventions

Low-force muscle stimulation

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.

Intervention Type: BEHAVIORAL

High-force muscle stimulation

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.

Intervention Type: BEHAVIORAL

Sequential low-force and high-force muscle stimulation

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.

Intervention Type: BEHAVIORAL

Eligibility Criteria

Exclusion Criteria

• Subjects will be excluded if they have pressure ulcers
• chronic infection
• lower extremity muscle contractures
• deep vein thrombosis
• recent limb fractures
• muscle metabolic disorders
• 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

• Minimum Eligible Age: 18 Years
• Maximum Eligible Age: 75 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

University of Iowa

OTHER

Sponsor Role: collaborator

VA Office of Research and Development

FED

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

Richard K Shields, PhD PT

Role: PRINCIPAL_INVESTIGATOR

Iowa City VA Health Care System, Iowa City, IA

Locations

Iowa City VA Health Care System, Iowa City, IA

Iowa City, Iowa, United States

Countries

United States

References

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.

Reference Type: BACKGROUND

PMID: 21171097 (View on PubMed)

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.

Reference Type: BACKGROUND

PMID: 21641545 (View on PubMed)

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.

Reference Type: BACKGROUND

PMID: 22507023 (View on PubMed)

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.

Reference Type: BACKGROUND

PMID: 23408218 (View on PubMed)

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.

Reference Type: RESULT

PMID: 22187008 (View on PubMed)

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.

Reference Type: RESULT

PMID: 24744911 (View on PubMed)

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.

Reference Type: RESULT

PMID: 25531450 (View on PubMed)

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.

Reference Type: RESULT

PMID: 25635001 (View on PubMed)

Other Identifiers

B7097-R

Identifier Type: -

Identifier Source: org_study_id