Skeletal Muscle Hypertrophy and Cardio-Metabolic Benefits After Spinal Cord Injury

February 26, 2021 updated by: Ashraf S. Gorgey, United States Department of Defense

Spinal cord injury (SCI) is a devastating medical problem that affects thousands of civilian and military personnel in the United States. Spinal cord injuries (SCI) predispose individuals to impaired fitness, obesity, glucose intolerance and insulin resistance, placing them at greater risk for diabetes and coronary artery disease. These are devastating problems that occur frequently because of changes in body composition and reduced level of physical activity. Skeletal muscle wasting plays a central role in altered metabolism after SCI. Functional electrical stimulation (FES) is an effective rehabilitation tool that has been used to train the paralyzed skeletal muscles and which has shown some ability to ameliorate the deleterious effects of SCI on metabolism, particularly on insulin sensitivity. However, its ability to reverse skeletal muscle wasting is modest; most studies report limited gains in muscle mass and workload with highly variables outcomes from one study to another. This proposal was stimulated by the findings that a program of neuromuscular electrical stimulation resistance exercise prior to initiating functional electrical stimulation lower extremity cycling (FES-LEC) improves the gains in muscle mass and workload observed with FES. The specific objectives for the current proposal are to compare the impact of FES following evoking skeletal muscle hypertrophy of the lower extremity versus initiating FES cycling without introducing the hypertrophy effects on insulin sensitivity, control of blood sugar levels, oxygen uptake and amounts of muscle tissue and fat deposition. These studies could potentially have significant effects on thousands of people that will experience an SCI in the future as well as those living with SCI where prolonged paralysis is a major quality of life issue.

There is a major need to investigate the mechanisms lead to maximize the benefits of FES applications and to understand cellular or molecular events that are associated with muscle hypertrophy and lead to promoting metabolic health after SCI. The designed study will provide a greater understanding regarding utilization of energy sources (like fats and sugars) in muscle

Study Overview

Status

Status

Indicates the current recruitment status or the expanded access status.
Completed

Conditions

Conditions

The disease, disorder, syndrome, illness, or injury that is being studied. On ClinicalTrials.gov, conditions may also include other health-related issues, such as lifespan, quality of life, and health risks.

Intervention / Treatment

Intervention / Treatment

A process or action that is the focus of a clinical study. Interventions include drugs, medical devices, procedures, vaccines, and other products that are either investigational or already available. Interventions can also include noninvasive approaches, such as education or modifying diet and exercise.

Detailed Description

Primary Objectives Aim #1: To determine the impact of 12+12 weeks of neuromuscular electrical stimulation (NMES)+FES-LEC on oxygen uptake, insulin sensitivity and glucose uptake in adults with SCI compared to control + FES-LEC.

Aim #2: To determine the impact of 12+12 weeks of NMES+FES-LEC on skeletal muscle size, infiltration of intramuscular fat, visceral adiposity as well as fatigue resistance compared to control+ FES-LEC.

. Aim #3 : To determine the impact of 12+12 weeks of NMES+FES-LEC on determinants of energy metabolism, protein molecules involved in insulin signaling, muscle hypertrophy and oxygen uptake (IRS-1, adenosine monophosphate kinase (AMPK), glucose transporter (GLUT-4), insulin like growth factor (IGF-1), Akt, mammalian target of rapamycin (mTOR) and Peroxisome proliferator-activated receptor coactivator (PGC-1 alpha) and electron transport chain proteins compared to control + FES-LEC only.

Subjects: Forty eight chronic (1 year or more post-injury) individuals with motor complete SCI will be recruited from the Hunter Holmes McGuire VA Spinal Cord Dysfunction registry and Virginia Commonwealth University over 4 years.

Inclusion Criteria

  1. All participants will be between 18-65 years old, men/women,
  2. greater than one year post SCI,
  3. Body mass index (BMI) < 30 Kg/m2.
  4. Participants must have C5-L2 level of injury, traumatic motor complete or incomplete SCI [American Spinal Injury Impairment Scale Classification (AIS A, B or C)].

Exclusion Criteria:

  1. Participants with any of the following pre-existing medical conditions will be excluded (cardiovascular disease, uncontrolled type II diabetes mellitus, uncontrolled hypertension, and those on insulin, pressures sores stage 3 or greater), hematocrit above 50% or urinary tract infection or symptoms.
  2. Participants with osteoporosis (T-score equal or worse than -2.5 according to the World Health recommendation) will be excluded.
  3. Pregnant women and women who will be involved and become pregnant during the course of the study will be excluded as well.

Study arms

  1. NMES+FES group (n =24; 2 days/week for 24 weeks); this group will undergo twice weekly of 12 weeks of surface NMES and ankle weights followed by 12 additional weeks of twice weekly of progressive FES-LEC using the RT300 bike. The total participation duration is 24 weeks +3 weeks for measurements.
  2. Control + FES group (n =24; 2 days/week for 24 weeks); this group will undergo twice weekly of 12 weeks of passive leg extension/flexion with no ankle weights followed by 12 additional weeks of twice weekly of progressive FES-LEC using the RT300 bike. The total participation duration is 24 weeks+3 weeks for measurements.

Study Type

Study Type

Describes the nature of a clinical study. Study types include interventional studies (also called clinical trials), observational studies (including patient registries), and expanded access.
Interventional

Enrollment (Anticipated)

Enrollment

The number of participants in a clinical study. The "anticipated" enrollment is the target number of participants that the researchers need for the study.
48

Phase

Phase

The stage of a clinical trial studying a drug or biological product, based on definitions developed by the U.S. Food and Drug Administration (FDA). The phase is based on the study's objective, the number of participants, and other characteristics. There are five phases: Early Phase 1 (formerly listed as Phase 0), Phase 1, Phase 2, Phase 3, and Phase 4. Not Applicable is used to describe trials without FDA-defined phases, including trials of devices or behavioral interventions.
  • Not Applicable

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Locations

  • United States
    • New York
      • Bronx, New York, United States
        • James J. Peters VA Medical Center
    • Virginia
      • Richmond, Virginia, United States, 23249
        • Hunter Holmes McGuire VA Medical Center
      • Richmond, Virginia, United States
        • Virginia Commonwealth Unviersity

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Eligibility Criteria

The key requirements that people who want to participate in a clinical study must meet or the characteristics they must have. Eligibility criteria consist of both inclusion criteria (which are required for a person to participate in the study) and exclusion criteria (which prevent a person from participating). Types of eligibility criteria include whether a study accepts healthy volunteers, has age or age group requirements, or is limited by sex.

Ages Eligible for Study

18 years to 65 years (Adult, Older Adult)

Accepts Healthy Volunteers

No

Genders Eligible for Study

All

Description

Inclusion Criteria:

  • All participants will be between 18-65 years old,
  • men/women,
  • Greater than one year post SCI,
  • with body mass index (BMI) < 30 Kg/m2. .
  • Participants must have traumatic motor complete or incomplete SCI C5-L2 level of injury, American Spinal Injury Impairment Scale Classification (AIS A, B or C).

Exclusion Criteria:

  • Participants with any of the following pre-existing medical conditions will be excluded (cardiovascular disease, uncontrolled type II DM, uncontrolled hypertension, and those on insulin, pressures sores stage 3 or greater), hematocrit above 50% or urinary tract infection or symptoms.
  • Participants with osteoporosis (T-score equal or worse than -2.5 according to the World Health recommendation) will be excluded.
  • Pregnant women and women who will be involved and become pregnant during the course of the study will be excluded as well.

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: Health Services Research
  • Allocation: Randomized
  • Interventional Model: Parallel Assignment
  • Masking: None (Open Label)

Arms and Interventions

Participant Group / Arm

Participant Group / Arm

A group or subgroup of participants in a clinical trial that receives a specific intervention/treatment, or no intervention, according to the trial's protocol.
Intervention / Treatment

Intervention / Treatment

A process or action that is the focus of a clinical study. Interventions include drugs, medical devices, procedures, vaccines, and other products that are either investigational or already available. Interventions can also include noninvasive approaches, such as education or modifying diet and exercise.
Experimental: NMES+FES group
NMES+FES group (n=24; 2 days/week for 24 weeks); this group will undergo twice weekly of 12 weeks of surface NMES and ankle weights followed by 12 additional weeks of twice weekly of progressive FES-LEC using the RT300 bike. The total participation duration is 24 weeks +3 weeks for measurements.
Device: NMES+FES
12 weeks of electrically evoked resistance training followed by 12 weeks of functional electrical stimulation cycling.
Other Names:
  • (NMES; Theratouch)+(FES; RTI300 Bike)
Experimental: Control+FES group
Control+FES group (n=24; 2 days/week for 24 weeks); this group will undergo twice weekly of 12 weeks of passive leg extension/flexion with no ankle weights followed by 12 additional weeks of twice weekly of progressive FES-LEC using the RT300 bike. The total participation duration is 24 weeks+3 weeks for measurements.
Device: Control+FES
12 weeks of passive movement followed by 12 weeks of functional electrical stimulation cycling.
Other Names:
  • Control+(FES; RTI300 Bike)

What is the study measuring?

Primary Outcome Measures

Primary Outcome Measures

In a clinical study's protocol, the planned outcome measure that is the most important for evaluating the effect of an intervention/treatment. Most clinical studies have one primary outcome measure, but some have more than one.
Outcome Measure
Measure Description
Time Frame
Glucose uptake
Time Frame: 24 weeks
by measuring glucose effectiveness
24 weeks
Insulin Sensitivity
Time Frame: 24 weeks
By performing frequent blood drawing of 32 samples over 3 hour period while the patient is fasting.
24 weeks
Oxygen Uptake
Time Frame: 24 weeks
24 weeks

Secondary Outcome Measures

Secondary Outcome Measures

In a clinical study's protocol, a planned outcome measure that is not as important as the primary outcome measure for evaluating the effect of an intervention but is still of interest. Most clinical studies have more than one secondary outcome measure.
Outcome Measure
Measure Description
Time Frame
Skeletal Muscle Size
Time Frame: 24 weeks
Magnetic Resonance Imaging
24 weeks
Visceral Fat
Time Frame: 24 weeks
Magnetic Resonance Imaging
24 weeks

Other Outcome Measures

Other Outcome Measures

For clinical trials, a planned measurement described in the protocol that is used to determine the effect of an intervention/treatment on participants. For observational studies, a measurement or observation that is used to describe patterns of diseases or traits, or associations with exposures, risk factors, or treatment. Types of outcome measures include primary outcome measure and secondary outcome measure.
Outcome Measure
Measure Description
Time Frame
Skeletal Muscle protein expressions
Time Frame: 24 weeks
Muscle Biopsy of the Vastus Lateralis Muscle. The Quantity of the Protein will be determined using Western Blot.
24 weeks
Mitochondrial Enzyme Activities
Time Frame: 24 weeks
Muscle Biopsy of the Vastus Lateralis Muscle. Mitochondrial enzyme activities will be determined using biochemical assays.
24 weeks

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

Sponsor

The organization or person who initiates the study and who has authority and control over the study.
United States Department of Defense

Collaborators

Collaborators

An organization other than the sponsor that provides support for a clinical study. This support may include activities related to funding, design, implementation, data analysis, or reporting.
Virginia Commonwealth University
James J. Peters Veterans Affairs Medical Center
Hunter Holmes McGuire VA Medical Center

Publications and helpful links

The person responsible for entering information about the study voluntarily provides these publications. These may be about anything related to the study.

General Publications

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start

Study Start

The actual date on which the first participant was enrolled in a clinical study. The "anticipated" study start date is the date that the researchers think will be the study start date.
October 1, 2015

Primary Completion (Actual)

Primary Completion

The date on which the last participant in a clinical study was examined or received an intervention to collect final data for the primary outcome measure. Whether the clinical study ended according to the protocol or was terminated does not affect this date. For clinical studies with more than one primary outcome measure with different completion dates, this term refers to the date on which data collection is completed for all the primary outcome measures. The "anticipated" primary completion date is the date that the researchers think will be the primary completion date for the study.
September 1, 2020

Study Completion (Actual)

Study Completion

The date on which the last participant in a clinical study was examined or received an intervention/treatment to collect final data for the primary outcome measures, secondary outcome measures, and adverse events (that is, the last participant's last visit). The "anticipated" study completion date is the date that the researchers think will be the study completion date.
September 1, 2020

Study Registration Dates

First Submitted

First Submitted

The date on which the study sponsor or investigator first submitted a study record to ClinicalTrials.gov. There is typically a delay of a few days between the first submitted date and the record's availability on ClinicalTrials.gov (the first posted date).
December 11, 2015

First Submitted That Met QC Criteria

First Submitted That Met QC Criteria

The date on which the study sponsor or investigator first submits a study record that is consistent with National Library of Medicine (NLM) quality control (QC) review criteria. The sponsor or investigator may need to revise and submit a study record one or more times before NLM's QC review criteria are met. It is the responsibility of the sponsor or investigator to ensure that the study record is consistent with the NLM QC review criteria.
January 20, 2016

First Posted (Estimate)

First Posted

The date on which the study record was first available on ClinicalTrials.gov after National Library of Medicine (NLM) quality control (QC) review has concluded. There is typically a delay of a few days between the date the study sponsor or investigator submitted the study record and the first posted date.
January 21, 2016

Study Record Updates

Last Update Posted (Actual)

Last Update Posted

The most recent date on which changes to a study record were made available on ClinicalTrials.gov. There may be a delay between when the changes were submitted to ClinicalTrials.gov by the study's sponsor or investigator (the last update submitted date) and the last update posted date.
March 1, 2021

Last Update Submitted That Met QC Criteria

Last Update Submitted That Met QC Criteria

The most recent date on which the study sponsor or investigator submitted changes to a study record that are consistent with National Library of Medicine (NLM) quality control (QC) review criteria. It is the responsibility of the sponsor or investigator to ensure that the study record is consistent with the NLM QC review criteria.
February 26, 2021

Last Verified

Last Verified

The most recent date on which the study sponsor or investigator confirmed the information about a clinical study on ClinicalTrials.gov as accurate and current. If a study with a recruitment status of recruiting; not yet recruiting; or active, not recruiting has not been confirmed within the past 2 years, the study's recruitment status is shown as unknown.
February 1, 2021

More Information

Terms related to this study

Additional Relevant MeSH Terms

Other Study ID Numbers

Other Study ID Numbers

Identifiers or ID numbers other than the NCT number that are assigned to a clinical study by the study's sponsor, funders, or others. These numbers may include unique identifiers from other trial registries and National Institutes of Health grant numbers.
  • W81XWH-14-SCIRP-CTA

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