Spinal Cord InjuriesSCINCT03204240
Metabolic Health in Individuals With Spinal Cord Injury (SCI)
A study testing Neuromuscular electrical stimulation in people with Spinal Cord Injuries and Skeletal Muscle Atrophy, run by Ohio State University at 1 site in United States.
Trial summary
Individuals with spinal cord injury (SCI) live longer than before and live to an age where metabolic disorders become highly prevalent. Due to loss of mobility and severe skeletal muscle atrophy, obesity, glucose intolerance, and peripheral insulin resistance develop soon after the onset of SCI. Read more about this study
- Who is it for?
- Ages 18 to 60 years
- Conditions the study is for
- Spinal Cord Injuries, Skeletal Muscle Atrophy, Metabolic Disease
- What is being tested?
- Neuromuscular electrical stimulation
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 40 participants
- Where
- 1 siteUnited States
- Study dates
- 1 Jan 2018to 31 Aug 2022
- Phase
- Interventional
- Are there results?
- None posted in the registry
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 to 60 years
- All sexes
- No healthy volunteers
- Adult
Who may be able to join
- 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.
Who cannot join
- 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
Trial locations and contacts
1 site in 1 country.
About this study
Official title: Targeting Skeletal Muscle to Improve Metabolic Health in Individuals With Spinal Cord Injury (SCI)
Individuals with spinal cord injury (SCI) live longer than before and live to an age where metabolic disorders become highly prevalent. Due to loss of mobility and severe skeletal muscle atrophy, obesity, glucose intolerance, and peripheral insulin resistance develop soon after the onset of SCI. These abnormalities are thought to contribute to the increased diabetes disease risk and accelerated aging process in the SCI population. As a result of these trends, overall burden of complications, economic impact and reduced quality of life are increasing. Until there are effective treatments for SCI, it is imperative to develop effective interventions to mitigate metabolic disorders that develop in individuals with SCI. The proposed research project examines the impact of early utilization of a novel neuromuscular electrical stimulation (NMES) program on skeletal muscle metabolism and overall metabolic health in individuals with sub-acute, complete SCI.
Read the 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.
- Being tested
- Neuromuscular electrical stimulation
- Keywords
- Spinal Cord Injury, Skeletal Muscle, Functional Electrical Stimulation, Diabetes
- Medical subject headings
- Spinal Cord Injuries, Muscular Atrophy, Metabolic Diseases, Diabetes Mellitus
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Neuromuscular electrical stimulationOther
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.
| Study group | Role | What they receive |
|---|---|---|
| Intervention | Experimental | 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. Receives: Other: Neuromuscular electrical stimulation |
| Control | No intervention | 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 being measured
The primary outcome is the main question the study is designed to answer.
Change in insulin sensitivity
Liquid meal test will be given and blood samples will be collected before and after meal ingestion.
Measured: Week1 and Week 6 of IPR
Change in glucose tolerance
Liquid meal test will be given and blood samples will be collected before and after meal ingestion.
Measured: Week 1 and Week 6 of IPR
Change in beta cell function
Liquid meal test will be given and blood samples will be collected before and after meal ingestion.
Measured: Week 1 and Week 6 of IPR
Secondary outcomes (3)
Change in metabolic signaling in skeletal muscle
Muscle samples will be collected via our established percutaneous needle biopsy procedure.
Measured: Week1 and Week 6 of IPR
Change in muscle strength
The quadriceps femoris muscle group will be studied during NMES-elicited muscle contractions both in the intervention and control groups.
Measured: Week 1 and Week 6 of IPR
Change in muscle fatigue
The quadriceps femoris muscle group will be studied during NMES-elicited muscle contractions both in the intervention and control groups.
Measured: Week 1 and Wekk 6 of IPR
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted29 Jun 2017
- Study start1 Jan 2018
- Primary completion29 Aug 2022
- Study completion31 Aug 2022
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Spinal Cord InjuriesStudies of the same condition, open and under way.
- More trials run by Ohio State UniversityThe sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase N/A
- Primary purpose
- Other
- Allocation
- Randomised
- Intervention model
- Crossover
- Masking
- Single blind
- Who is masked
- Outcomes assessor
- Enrolment
- 40 participants (actual)
Sponsor and investigators
- Lead sponsor
- Ohio State University
- Sponsor type
- University, hospital or other
- Responsible party
- Principal investigator, Ceren Yarar-Fisher, Ohio State University
- Investigators
- Ceren Yarar-Fisher, PhD, Principal investigator, OSU
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT03204240
- Sponsor's protocol ID
- 000512788
- Acronym
- SCI
- Status last verified
- Mar 2023
- First submitted
- 14 Jun 2017
- Last updated
- 27 Mar 2023
- Results posted
- No
- Data monitoring committee
- No
- FDA-regulated drug
- No
- FDA-regulated device
- No
- Individual data sharing
- Undecided
Study at a glance
From the registry record, last updated by the sponsor on 27 Mar 2023. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Targeting Skeletal Muscle to Improve Metabolic Health in Individuals With Spinal Cord Injury (SCI)
- ClinicalTrials.gov ID
- NCT03204240
- Acronym / sponsor ID
- SCI / 000512788
- Keywords
- Spinal Cord Injury, Skeletal Muscle, Functional Electrical Stimulation, Diabetes
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 40 participants (actual)
- Lead sponsor
- Ohio State UniversityUniversity, hospital or other
- Study start
- 1 Jan 2018 (actual)
- Primary completion
- 29 Aug 2022 (actual)
- Study completion
- 31 Aug 2022 (actual)
- First posted
- 29 Jun 2017 (actual)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
Individuals with spinal cord injury (SCI) live longer than before and live to an age where metabolic disorders become highly prevalent. Due to loss of mobility and severe skeletal muscle atrophy, obesity, glucose intolerance, and peripheral insulin resistance develop soon after the onset of SCI. These abnormalities are thought to contribute to the increased diabetes disease risk and accelerated aging process in the SCI population. As a result of these trends, overall burden of complications, economic impact and reduced quality of life are increasing. Until there are effective treatments for SCI, it is imperative to develop effective interventions to mitigate metabolic disorders that develop in individuals with SCI. The proposed research project examines the impact of early utilization of a novel neuromuscular electrical stimulation (NMES) program on skeletal muscle metabolism and overall metabolic health in individuals with sub-acute, complete SCI.
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 design
- Primary purpose
- Other
- Allocation
- Randomised
- Intervention model
- Crossover
- Masking
- Single blind (outcomes assessor)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| Intervention | Experimental | Other: Neuromuscular electrical stimulationThis 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. |
| Control | No intervention | –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. |
Who may qualify
- Ages
- 18 to 60 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult
Key inclusion criteria (5 listed)
- 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.
Key exclusion criteria (5 listed)
- 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
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| Neuromuscular electrical stimulationNMES-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. | Other | Intervention |
Primary outcome
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.
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.
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.
3 secondary outcomes
Change in metabolic signaling in skeletal muscle
Time frame: Week1 and Week 6 of IPR
Change in muscle strength
Time frame: Week 1 and Week 6 of IPR
Change in muscle fatigue
Time frame: Week 1 and Wekk 6 of IPR
Results and safety
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 27 Mar 2023.
- Individual participant dataSharing planned: Undecided
Related trials for Spinal Cord Injuries
Recruiting
MyHand-SCI: An Active Hand Orthosis for Spinal Cord Injury
Spinal Cord Injuries, Tetraplegia
Recruiting
Clinical Outcome Assessment for AT & BCI
Spinal Cord Injury, ALS (Amyotrophic Lateral Sclerosis)
Recruiting
Transcutaneous Spinal Cord Stimulation Combined With 4-Aminopyridine and Intensive Rehabilitation in SCI
Spinal Cord Injuries
Not yet recruiting
Evaluating the Effect of the Zeen Mobility Device on Clinical Practicality, Safety, and Impact (Via Assessments of Walking, Standing Tolerance, Balance, Endurance, Effort, and Participation in Daily Tasks) in an Outpatient Rehabilitation Setting for Individuals With Mobility Impairments.
Stroke, Parkinson's Disease (PD)
RecruitingPhase 3
A Trial Investigating the Efficacy and Safety of NVG-291 in Subjects With Chronic Spinal Cord Injury
Chronic Spinal Cord Injury
Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Ceren Yarar-Fisher, PhD principal investigator
OSU
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A study testing Neuromuscular electrical stimulation in people with Spinal Cord Injuries and Skeletal Muscle Atrophy, run by Ohio State University at 1 site in United States.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 5 inclusion and 5 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: finished, as of the sponsor's last update on 27 Mar 2023. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in United States. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
Are results available for this study?
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Change in insulin sensitivity (time frame: Week1 and Week 6 of IPR). The study lists 3 primary outcomes in all. It is what the study was designed to measure, not a finding.
Where can I read the original study information?
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 27 Mar 2023.