Novel Intervention to Influence Muscle Plasticity in Veterans

This study is currently recruiting participants. (see Contacts and Locations)
Verified March 2014 by Department of Veterans Affairs
Sponsor:
Collaborator:
University of Iowa
Information provided by (Responsible Party):
Department of Veterans Affairs
ClinicalTrials.gov Identifier:
NCT01093014
First received: March 23, 2010
Last updated: March 18, 2014
Last verified: March 2014
  Purpose

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. Our 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. We 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. We wish to discover the most effective method to maintain the molecular and physiologic properties of paralyzed muscle. We believe such a method will be in urgent demand as a co-intervention with pharmaceutical strategies in post-SCI rehabilitation.


Condition Intervention
Spinal Cord Injuries
Behavioral: Active Resisted Standing

Study Type: Interventional
Study Design: Allocation: Non-Randomized
Endpoint Classification: Efficacy Study
Intervention Model: Single Group Assignment
Masking: Open Label
Primary Purpose: Treatment
Official Title: Novel Intervention to Influence Muscle Plasticity in Veterans

Resource links provided by NLM:


Further study details as provided by Department of Veterans Affairs:

Primary Outcome Measures:
  • 1) Quadriceps physiology: (peak force, fatigue index, torque-time integral, and potentiation index). [ Time Frame: 16 weeks ] [ Designated as safety issue: No ]

Secondary Outcome Measures:
  • Muscle tissue analyses (mRNA fold-changes) [ Time Frame: 16 ] [ Designated as safety issue: No ]
  • Quadriceps mRNA fold-changes for atrophy/hypertrophy pathways. [ Time Frame: 16 weeks ] [ Designated as safety issue: No ]

Estimated Enrollment: 150
Study Start Date: April 2011
Estimated Study Completion Date: December 2014
Estimated Primary Completion Date: December 2014 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: Arm 1
Higher-force (20 Hz) unilateral training
Behavioral: Active Resisted Standing
The active standing intervention includes both a lab based system and a portable home-based training system. Subjects will perform active-resisted standing on 5 days per wk. The high force group will activate the quads with a 20 Hz stimulation train every 12 secs for 4 secs. The low force group will activate the quads with a 10 Hz stimulation frequency train every 24 sec for 8 secs. Two bouts of 60 contractions will be admin 5 days/wk for 12 wks. The initial current will be set to the intensity that generates 60% of the maximal peak twitch. The intensity will be adjusted each wk as the peak twitch increases with hypertrophy. Subjects in Aims 1 and 2 will train unilateral quads. A second cohort of subjects will train bilateral quads for Aim 3. Unilateral and bilateral training subjects will perform home-based training on 4 days per wk. On one day per wk they will return to the laboratory for a training/testing session, bringing the total dose of training to 5 days per wk.
Experimental: Arm 2
Lower-force (10 Hz) unilateral training
Behavioral: Active Resisted Standing
The active standing intervention includes both a lab based system and a portable home-based training system. Subjects will perform active-resisted standing on 5 days per wk. The high force group will activate the quads with a 20 Hz stimulation train every 12 secs for 4 secs. The low force group will activate the quads with a 10 Hz stimulation frequency train every 24 sec for 8 secs. Two bouts of 60 contractions will be admin 5 days/wk for 12 wks. The initial current will be set to the intensity that generates 60% of the maximal peak twitch. The intensity will be adjusted each wk as the peak twitch increases with hypertrophy. Subjects in Aims 1 and 2 will train unilateral quads. A second cohort of subjects will train bilateral quads for Aim 3. Unilateral and bilateral training subjects will perform home-based training on 4 days per wk. On one day per wk they will return to the laboratory for a training/testing session, bringing the total dose of training to 5 days per wk.
Experimental: Arm 3
Higher-force (20 Hz) bilateral training
Behavioral: Active Resisted Standing
The active standing intervention includes both a lab based system and a portable home-based training system. Subjects will perform active-resisted standing on 5 days per wk. The high force group will activate the quads with a 20 Hz stimulation train every 12 secs for 4 secs. The low force group will activate the quads with a 10 Hz stimulation frequency train every 24 sec for 8 secs. Two bouts of 60 contractions will be admin 5 days/wk for 12 wks. The initial current will be set to the intensity that generates 60% of the maximal peak twitch. The intensity will be adjusted each wk as the peak twitch increases with hypertrophy. Subjects in Aims 1 and 2 will train unilateral quads. A second cohort of subjects will train bilateral quads for Aim 3. Unilateral and bilateral training subjects will perform home-based training on 4 days per wk. On one day per wk they will return to the laboratory for a training/testing session, bringing the total dose of training to 5 days per wk.
Experimental: Arm 4
Lower-force (10 Hz) bilateral training
Behavioral: Active Resisted Standing
The active standing intervention includes both a lab based system and a portable home-based training system. Subjects will perform active-resisted standing on 5 days per wk. The high force group will activate the quads with a 20 Hz stimulation train every 12 secs for 4 secs. The low force group will activate the quads with a 10 Hz stimulation frequency train every 24 sec for 8 secs. Two bouts of 60 contractions will be admin 5 days/wk for 12 wks. The initial current will be set to the intensity that generates 60% of the maximal peak twitch. The intensity will be adjusted each wk as the peak twitch increases with hypertrophy. Subjects in Aims 1 and 2 will train unilateral quads. A second cohort of subjects will train bilateral quads for Aim 3. Unilateral and bilateral training subjects will perform home-based training on 4 days per wk. On one day per wk they will return to the laboratory for a training/testing session, bringing the total dose of training to 5 days per wk.
No Intervention: Arm 5
Control

Detailed Description:

Central Hypothesis: We 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.

  Eligibility

Ages Eligible for Study:   18 Years to 75 Years
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  • 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.

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
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT01093014

Contacts
Contact: Michele Myrvik (319) 339-7151 Michele.Myrvik@va.gov
Contact: Richard K Shields, PhD PT Richard.Shields@va.gov

Locations
United States, Iowa
VA Medical Center, Iowa City Recruiting
Iowa City, Iowa, United States, 52246-2208
Contact: Michele Myrvik    319-339-7151    Michele.Myrvik@va.gov   
Contact: Kari A Steinkamp    (319) 338-0581 ext 7678    Kari.Steinkamp2@va.gov   
Principal Investigator: Richard K Shields, PhD PT         
Sponsors and Collaborators
University of Iowa
Investigators
Principal Investigator: Richard K Shields, PhD PT VA Medical Center, Iowa City
  More Information

Publications:
Responsible Party: Department of Veterans Affairs
ClinicalTrials.gov Identifier: NCT01093014     History of Changes
Other Study ID Numbers: B7097-R, 5R01HD062507-04
Study First Received: March 23, 2010
Last Updated: March 18, 2014
Health Authority: United States: Federal Government

Keywords provided by Department of Veterans Affairs:
Quadriceps Muscle
RNA, Messenger
Hypertrophy
Electric Stimulation Therapy

Additional relevant MeSH terms:
Spinal Cord Injuries
Wounds and Injuries
Spinal Cord Diseases
Central Nervous System Diseases
Nervous System Diseases
Trauma, Nervous System

ClinicalTrials.gov processed this record on July 09, 2014