- ICH GCP
- US Clinical Trials Registry
- Clinical Trial NCT03204240
Metabolic Health in Individuals With Spinal Cord Injury (SCI) (SCI)
Targeting Skeletal Muscle to Improve Metabolic Health in Individuals With Spinal Cord Injury (SCI)
Study Overview
Status
Intervention / Treatment
Detailed Description
The escalating prevalence of metabolic disorders in individuals with long-standing spinal cord injury (SCI) highlights the urgent need for early interventions for prevention and improving quality of life. Individuals with SCI, while often relatively young, are at high risk for developing insulin resistance and type 2 diabetes soon after the onset of injury. Skeletal muscle is the major site of dietary glucose disposal, yet the relationship between adaptations in skeletal muscle after SCI and the development of metabolic disturbances remains poorly understood. Within 6 months after SCI, lower limb muscles atrophy by up to 45% and individuals show a 3-fold increase in intramuscular fat levels compared to able-bodied (AB) controls. Moreover, within 6 months after SCI, fatigue-resistant and oxidative Type I and Type IIa muscle fibers transform into highly fatigable, glycolytic Type IIax and IIx muscle fibers with impaired oxidative metabolism. The maintenance of adequate muscle mass and metabolic function has never been targeted as a potential strategy to prevent chronic metabolic disorders in individuals with SCI. Early prevention of these deleterious adaptations is expected to be more effective than attempting to reverse changes several months or years after SCI.
Among the available experimental strategies to reverse atrophy and improve skeletal muscle metabolism in individuals with SCI, there seems to be consensus that muscle contraction via neuromuscular electrical stimulation (NMES) is the most potent approach. The investigators recently showed that 8 weeks of NMES-resistance exercise in people with long-standing SCI effectively increased myofiber size and distribution of Type IIa myofibers; however, this intervention did not increase the distribution of Type I fibers. There is a need for novel NMES programs that induce key molecular adaptations to both resistance and aerobic exercise to maintain an oxidative, fatigue-resistant, and insulin-sensitive phenotype following SCI.
Here, the investigators propose an early intervention of combined NMES (Comb-NMES). This program couples electrically induced resistance and aerobic exercise on the knee extensor muscle group (quadriceps) with the goal of maintaining or even improving muscle mass and metabolic function. The proposed Comb-NMES program repetitively stresses the paralyzed knee extensor muscles with both low frequency electrical stimulation (aerobic training) to improve oxidative metabolism and retain Type I fibers and high frequency (resistance training) electrical stimulation with dynamic contractions to prevent atrophy and retain Type IIa fibers.
The investigators will test the following central hypothesis that, compared to a control group, those treated with Comb-NMES for 6 weeks early after SCI will maintain a better whole-body metabolic profile, largely driven by maintenance of paralyzed muscle mass, fiber phenotype (maintenance of Type I and IIa fibers), and muscle oxidative metabolic function. The investigators will test this hypothesis in a controlled clinical trial of patients with SCI with the following specific aims:
Aim 1: Quantify the effects of Comb-NMES on clinically important measures of metabolic function.
Hypothesis 1. Compared to a control group, 6 weeks of Comb-NMES (3 days/week) will maintain higher glucose tolerance and whole-body insulin sensitivity.
Aim 2: Quantify cellular, molecular and functional adaptations in the quadriceps muscle that are responsible for improvements in muscle metabolism and overall metabolic profile.
Hypothesis 2.1. Compared to a control group, 6 weeks of Comb-NMES (3 days/week) will maintain better muscle glucose utilization, oxidative metabolism, muscle size, strength, and fatigue resistance, as well as a healthy muscle fiber phenotype (homogeneous distribution of Type I, IIa, and IIx fibers).
Hypothesis 2.2. Comb-NMES-induced improvements in overall metabolic profile will be reflected in changes in metabolite signatures related to muscle mitochondrial function and intermediary metabolism.
Study Type
Enrollment (Actual)
Phase
- Not Applicable
Contacts and Locations
Study Locations
-
-
Alabama
-
Birmingham, Alabama, United States, 35294
- UAB
-
-
Participation Criteria
Eligibility Criteria
Ages Eligible for Study
Accepts Healthy Volunteers
Genders Eligible for Study
Description
Inclusion Criteria:
- between the ages of 18 and 60 years;
- diagnosis of traumatic SCI at the cervical or thoracic level (C5-T12) classified as AIS A (motor and sensory complete);
- within 14 days of the SCI and the first week of initial inpatient rehabilitation;
- medically stable at the time of testing;
- no history of metabolic syndrome and/or type 1 or type 2 diabetes.
Exclusion Criteria:
- Pregnant women
- Orthopedic condition that limits lower extremity function
- Neurological (other than SCI), vascular, or cardiac problems that may limit function and interfere with testing procedures
- Have 1 or more contraindications to NMES
- Have lidocaine or iodine allergy
Study Plan
How is the study designed?
Design Details
- Primary Purpose: Other
- Allocation: Randomized
- Interventional Model: Crossover Assignment
- Masking: Single
Arms and Interventions
Participant Group / Arm |
Intervention / Treatment |
---|---|
Experimental: Intervention
This group will receive electrical stimulation induced exercises in addition to their standard care during in-patient rehabilitation (IPR).
Standard care will include respiration therapy, bed mobility, transfers, wheelchair mobility skills, bowel and bladder management, tone and spasticity management, and skills for performing other activities of daily living.
Exercises will include neuromuscular electrical stimulation (NMES) induced-resistance exercise (RE) (1x/day) and NMES-aerobic exercise (1x/day) for 3 days/week.
|
NMES-RE will involve concentric/eccentric contractions of the quadriceps from a seated position.
Briefly, each session will include four sets of 10 actions evoked using 50 Hz trains of 450 µs biphasic pulses.
The protocol will be implemented using surface NMES.
Upon completion of the NMES-RE session, participants will be given a short break (10-15 minutes) for recovery before starting aerobic training.
NMES aerobic exercise will involve twitch electrical stimulation (pulse duration/interval=200/50 µs) applied to the quadriceps muscle via surface NMES.
The current amplitude will set to 175 mA.
The training will start with 10 minutes of twitch stimulation at 2 Hz.
After the first weeks, the duration of the session will progressively increase up to 60 minutes at 10 Hz.
|
No Intervention: Control
This group will receive standard care plus passive dynamic exercise of the lower legs (sham treatment for NMES-RE, 1x/day) and transcutaneous electrical nerve stimulation (TENS, sham treatment for NMES-aerobic exercise, 1x/day) during IPR.
|
What is the study measuring?
Primary Outcome Measures
Outcome Measure |
Measure Description |
Time Frame |
---|---|---|
Change in insulin sensitivity
Time Frame: Week1 and Week 6 of IPR
|
Liquid meal test will be given and blood samples will be collected before and after meal ingestion.
|
Week1 and Week 6 of IPR
|
Change in glucose tolerance
Time Frame: Week 1 and Week 6 of IPR
|
Liquid meal test will be given and blood samples will be collected before and after meal ingestion.
|
Week 1 and Week 6 of IPR
|
Change in beta cell function
Time Frame: Week 1 and Week 6 of IPR
|
Liquid meal test will be given and blood samples will be collected before and after meal ingestion.
|
Week 1 and Week 6 of IPR
|
Secondary Outcome Measures
Outcome Measure |
Measure Description |
Time Frame |
---|---|---|
Change in metabolic signaling in skeletal muscle
Time Frame: Week1 and Week 6 of IPR
|
Muscle samples will be collected via our established percutaneous needle biopsy procedure.
|
Week1 and Week 6 of IPR
|
Change in muscle strength
Time Frame: Week 1 and Week 6 of IPR
|
The quadriceps femoris muscle group will be studied during NMES-elicited muscle contractions both in the intervention and control groups.
|
Week 1 and Week 6 of IPR
|
Change in muscle fatigue
Time Frame: Week 1 and Wekk 6 of IPR
|
The quadriceps femoris muscle group will be studied during NMES-elicited muscle contractions both in the intervention and control groups.
|
Week 1 and Wekk 6 of IPR
|
Collaborators and Investigators
Sponsor
Investigators
- Principal Investigator: Ceren Yarar-Fisher, PhD, OSU
Study record dates
Study Major Dates
Study Start (Actual)
Primary Completion (Actual)
Study Completion (Actual)
Study Registration Dates
First Submitted
First Submitted That Met QC Criteria
First Posted (Actual)
Study Record Updates
Last Update Posted (Actual)
Last Update Submitted That Met QC Criteria
Last Verified
More Information
Terms related to this study
Additional Relevant MeSH Terms
Other Study ID Numbers
- 000512788
Plan for Individual participant data (IPD)
Plan to Share Individual Participant Data (IPD)?
Drug and device information, study documents
Studies a U.S. FDA-regulated drug product
Studies a U.S. FDA-regulated device product
This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.
Clinical Trials on Spinal Cord Injuries
-
Khon Kaen UniversityUnknownInjuries, Spinal Cord
-
Universidade do Vale do ParaíbaCompletedInjuries, Spinal Cord
-
Ekso BionicsBurke Medical Research InstituteCompletedInjuries, Spinal CordUnited States
-
ReWalk Robotics, Inc.Unknown
-
InVivo TherapeuticsTerminated
-
Shepherd Center, Atlanta GACompletedInjuries, Spinal Cord
-
Wroclaw Medical UniversityInstitute of Immunology and Experimental Therapy of the Polish Academy of... and other collaboratorsUnknownComplete Spinal Cord InjuriesPoland
-
M.D. Anderson Cancer CenterActive, not recruitingMetastatic Epidural Spinal Cord CompressionUnited States
Clinical Trials on Neuromuscular electrical stimulation
-
Brooks RehabilitationTerminatedBlepharoptosis | LagophthalmosUnited States
-
University Hospital, BrestRecruitingAsthma | Chronic Obstructive Pulmonary Disease Overlap SyndromeFrance
-
Hacettepe UniversityNot yet recruiting
-
MetroHealth Medical CenterEunice Kennedy Shriver National Institute of Child Health and Human Development... and other collaboratorsCompletedStroke | Hemiparesis | FootdropUnited States
-
University of Sao PauloSuspendedRehabilitation | Critical CareBrazil
-
Research Institute for Complex Problems of Cardiovascular...UnknownHeart Failure | Sarcopenia | Peripheral Artery Disease | Exercise IntoleranceRussian Federation
-
Federal University of Rio Grande do SulEnrolling by invitation
-
University of Texas, El PasoRecruitingObesity | Overweight | Insulin ResistanceUnited States
-
University of PittsburghKing Fahad Specialist Hospital Dammam; Saudi Arabian Cultural MissionCompleted