Novel Intervention to Influence Muscle Plasticity in Veterans

NCT01093014 | Completed Results

• 1 other identifier: B7097-R
• Study Type: interventional
• Target: 33
• Locations: 1 country
• Sites: 1

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.

Conditions

Spinal Cord Injuries

Keywords

Quadriceps Muscle; RNA, Messenger; Hypertrophy; Electric Stimulation Therapy

Outcome Measures

Primary Outcomes (4)

• 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

Study Arms (3)

Arm 1: High-force muscle stimulation

EXPERIMENTAL

High-force muscle stimulation

Behavioral: High-force muscle stimulation

Arm 2: Low-force muscle stimulation

EXPERIMENTAL

Low-force muscle stimulation

Behavioral: Low-force muscle stimulation

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

EXPERIMENTAL

Sequential low-force and high-force muscle stimulation

Behavioral: Sequential low-force and high-force muscle stimulation

Interventions

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.

Arm 2: Low-force muscle stimulation

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.

Arm 1: High-force muscle stimulation

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.

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

Eligibility Criteria

• Age: 18 Years - 75 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may not qualify if:

• 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

Sponsors & Collaborators

• VA Office of Research and Development: lead
• University of Iowa: collaborator

Study Sites (1)

Iowa City VA Health Care System, Iowa City, IA

Iowa City, Iowa, 52246-2208, United States

Location

Related Publications (8)

• 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.

  PMID: 21171097 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.

  PMID: 21641545 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.

  PMID: 22507023 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.

  PMID: 23408218 BACKGROUND

• 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.

  PMID: 22187008 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.

  PMID: 24744911 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.

  PMID: 25531450 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.

  PMID: 25635001 RESULT

MeSH Terms

Conditions

Spinal Cord Injuries; Hypertrophy

Condition Hierarchy (Ancestors)

Spinal Cord Diseases; Central Nervous System Diseases; Nervous System Diseases; Trauma, Nervous System; Wounds and Injuries; Pathological Conditions, Anatomical; Pathological Conditions, Signs and Symptoms

Results Point of Contact

• Title: Richard K. Shields PhD, PT
• Organization: University of Iowa / Iowa City VA Medical Center

richard-shields@uiowa.edu

319-335-9791

Study Officials

• Richard K Shields, PhD PT

  Iowa City VA Health Care System, Iowa City, IA

  PRINCIPAL INVESTIGATOR

Publication Agreements

• PI is Sponsor Employee: Yes

Study Design

• Study Type: interventional
• Phase: not applicable
• Allocation: NON RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: FED
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: March 23, 2010
• First Posted: March 25, 2010
• Study Start: April 1, 2011
• Primary Completion: December 1, 2014
• Study Completion: December 1, 2014
• Last Updated: March 10, 2016
• Results First Posted: February 5, 2016

Record last verified: 2016-02

Data Sharing

• IPD Sharing: Will not share

Locations

US (1)