Exoskeletal-assisted Walking Combined With Transcutaneous Spinal Cord Stimulation: Effect on Imaging and Serum Biomarkers of Skeletal Muscle Mass and Bone Strength.

July 20, 2026 updated by: VA Office of Research and Development

Exoskeletal-assisted Walking Combined With Transcutaneous Spinal Cord Stimulation: Effect on Imaging and Serum Biomarkers of Skeletal Muscle Mass and Bone Strength

Immobilization following spinal cord injury (SCI) results in muscle and bone loss below the level of injury, which ultimately predisposes to fracture at several sites throughout the legs and can lead to several medical complications that can devastate quality of life. There is a scarcity of research that has successfully implemented rehabilitation and/or exercise training interventions to preserve the musculoskeletal system during the acute phase SCI, or possibly reverse the muscle and bone loss that has already occurred in chronic SCI. This study will compare the effect of exoskeleton-assisted walking (EAW) training combined with transcutaneous spinal cord stimulation (tSCS) (EAW + active tSCS), to that of EAW + sham tSCS, on measures of muscle and bone health in a cohort of chronically injured motor incomplete SCI. A successful outcome would expand treatment options to improve musculoskeletal health over the lifetime.

Study Overview

Status

Status

Indicates the current recruitment status or the expanded access status.
Not yet recruiting

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

Background: Immobilization results in bone loss that predisposes to osteoporosis and fracture, which may be complicated by non-union, infection, and deep venous thrombosis. Reduced muscular contraction after SCI and the elevated release of cortisol contribute to a catabolic state, resulting in a loss of lean tissue mass (LTM) below the level of lesion. Six months after motor-complete SCI, the average muscle cross-sectional area (CSA) significantly decreases at the quadriceps, hamstrings, and hip adductors (14-16%), and 12% and 24% at the soleus and gastrocnemius, respectively. Following SCI, the quadricep muscles generate less total force and force per unit area when evoked by surface electrode electrical stimulation. This loss of muscle CSA and strength in the lower extremities limits the ability to stand, ambulate, and preserve bone - even if neural regenerative strategies could be implemented in the future. In addition to the marked skeletal muscle atrophy, persons with non-ambulatory motor-complete SCI also experience a precipitous loss of bone mineral content (BMC) and bone mineral density (BMD) by as much as 1% per week below the level of lesion. In individuals with motor-incomplete lesions who have not reached their ambulatory potential, there is still considerable bone loss due to immobilization that can reach the fracture threshold years after injury. This rapid bone loss during the first two years after SCI results in volumetric BMD (vBMD) at the DF and PT decreasing by ~ 50% and 26% at the trabecular and cortical compartments, respectively. During the chronic phase of SCI bone loss continues more slowly throughout the individuals lifetime. This loss in muscle and bone places individuals with SCI at high risk for fragility fracture. More than 50% of individuals with SCI experience a fragility fracture over the course of their lifetimes. Objectives: Aim 1: To compare the effects of 108 sessions of EAW + sham tSCS versus EAW + active tSCS on the muscle-bone unit in wheelchair-dependent chronic SCI participants.Aim 2 (exploratory): To determine the acute time-course responses for serum/plasma biomarkers of bone resorption and formation, muscle contractile activity, and the mRNA profiles of circulating exosomes collected prior to (time 0), and again 30, 60, 120, 180, minutes and 24, and 48 hours following an acute session of both the EAW + active tSCS and EAW + sham tSCS training interventions. Setting: Participant enrollment, the clinical trial intervention (EAW + sham tSCS versus EAW + active tSCS), EMG data collection, dual energy X-ray absorptiometry (DXA), peripheral quantitative computed tomography (pQCT), magnetic resonance imaging (MRI) to measure the cross-sectional area of the mid-thigh, and the time-course responses for serum/plasma biomarkers of bone resorption and formation and muscle contractile activity will be performed at the Kessler Foundation and the James J. Peters VA Medical Center.Design: After meeting eligibility criteria, wheelchair users with chronic SCI will be block randomized into the EAW + active tSCS group or the EAW + sham tSCS group (n=12 in each group). Both groups will receive 60 minutes of EAW overground training per session for a total of 108 sessions (3 X week for 36 weeks). In addition to the EAW training, the EAW + active tSCS group will receive simultaneous lumbosacral tSCS targeted to activate the locomotor central pattern generator. Participants: Twenty-four participants (12 participants/group) with SCI will be recruited over a 4-year period and randomly assigned to an EAW + sham tSCS or EAW + active tSCS group. At the end of the first year, approximately 3 participants will have completed the protocol. Outcome measures: At baseline, the investigators will perform imaging to measure bone density and strength, surface EMG to assess muscle contractility, and a time-course response for serum muscle and bone biomarkers following an acute bout of EAW. The investigators will capture these same data again after ~54 training sessions (mid-point), and after 108 training sessions (month 9 timepoint). In addition, MRI of both legs for muscle CSA will be performed at the baseline and month 9 time point.

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 (Estimated)

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.
24

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 Contact

Study Contact

The name and contact information for the person who can answer enrollment questions for a clinical study. Each location where the study is being conducted may also have a specific contact, who may be better able to answer those questions.

Study Contact Backup

Study Locations

  • United States
    • New Jersey
    • New York
      • The Bronx, New York, United States, 10468-3904
        • James J. Peters VA Medical Center, Bronx, NY
        • Contact:
        • Contact:
        • Principal Investigator:
          • Chris Cirnigliaro, MS

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

  • Adult

Accepts Healthy Volunteers

No

Description

Inclusion Criteria:

  • Non-walkers with an SCI greater than 3 years post injury
  • As measured by a member of the study staff, participants who have a lower extremity motor score greater or equal to 16 on the INSCSCI exam with an impairment grade of C or D
  • Neurologic level of injury as determined by study staff between C5-T10 (completed at participant's screening)
  • Capable of gripping Lofstrand crutches and/or a walker without assistance
  • Wheelchair reliant 100% of the time
  • Height is between 62 inches and 74 inches
  • Weight less than 220lbs

  • Anthropometric compatibility with the EAW device:

    • Thigh length between 14 and 19 in (36 and 48 cm)
    • Shank length between 17 and 22 in (43 and 55 cm)

Exclusion Criteria:

  • As determined by the study physician from the screening health exam, a history of fragility or traumatic fractures, unhealed fractures, and signs of swelling, bruising, and discoloration of the legs
  • Current bone disease diagnosis (e.g., osteomyelitis, hyperparathyroidism)
  • As determined by the study physician from the screening DXA study, a T-score at the total hip < -3.5 or aBMD of the knee (proximal tibia and/or distal femur) < 0.60 g/cm2 from the DXA screen
  • Positive pregnancy test at any of the study intervention or assessment visits, or if female participants plan to become pregnant over the course of the study, they will be excluded or withdrawn (if already enrolled) from participation
  • Currently in a gym/rehabilitation program performing ambulatory interventions such as EAW, as determined by the study staff
  • Currently prescribed any medications that can affect muscle and/or bone metabolism, as determined by the study staff

Exclusion Criteria from MRI Safety Screening:

  • Medically unsafe to receive an MRI scan
  • Claustrophobia
  • Baclofen pump

  • Body metal, including any of the following:

    • metal fragments or pieces in eyes or any other part of body
    • pacemakers or other implanted electrical devices
    • aneurysm clips (metal clips on wall of a large artery)
    • metallic prostheses (metal pins and heart valves)
    • internal hearing aids (cochlear implants)
    • permanent eyeliner
    • shrapnel fragments
    • piercing that cannot be removed

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: Treatment
  • 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: Exoskeleton-Assisted Walking (EAW) + active Transcutaneous Spinal Cord Stimulation (tSCS)
The EAW + active tSCS group will receive simultaneous lumbosacral tSCS while simultaneously performing EAW.
Device: Exoskeleton-Assisted Walking (EAW)
Participants will perform EAW will for 60 minutes per session for a total of 108 sessions (3 X week for 36 weeks).
Device: Active Transcutaneous Spinal Cord Stimulation (tSCS)
Participants in the active tSCS group will receive simultaneous lumbosacral tSCS while simultaneously performing EAW.
Sham Comparator: Exoskeleton-assisted walking (EAW) + sham Transcutaneous Spinal Cord Stimulation (tSCS)
The EAW + sham tSCS group will receive simultaneous lumbosacral sham tSCS while simultaneously performing EAW. Participants in both groups will receive 60 minutes of EAW + sham tSCS overground training per session for a total of 108 sessions (3 X week for 36 weeks).
Device: Exoskeleton-Assisted Walking (EAW)
Participants will perform EAW will for 60 minutes per session for a total of 108 sessions (3 X week for 36 weeks).
Device: Sham Transcutaneous Spinal Cord Stimulation (tSCS)
The lumbosacral tSCS electrical signal is set too low to have any biological effect while simultaneously performing EAW.

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
Muscle cross sectional area of the mid-thigh
Time Frame: Obtained prior to starting the study at enrollment (baseline) and again at the 9 month study time point (post intervention).
EAW + active tSCS will increase muscle cross sectional area of the mid-thigh more than EAW + sham tSCS.
Obtained prior to starting the study at enrollment (baseline) and again at the 9 month study time point (post intervention).

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
Bone Strength at the Distal Femur and Proximal Tibia
Time Frame: Obtained prior to starting the study at enrollment (baseline), at the 4.5 month study time point (mid-point), with a final measurement completed at the 9 month study time point (post intervention).
EAW + active tSCS will increase bone strength at the distal femur and proximal tibia more than EAW + sham tSCS.
Obtained prior to starting the study at enrollment (baseline), at the 4.5 month study time point (mid-point), with a final measurement completed at the 9 month study time point (post intervention).
Muscle and Bone Serum and Plasma Biomarker Time-Course Response
Time Frame: Obtained prior to starting the study at enrollment (baseline), at the 4.5 month study time point (mid-point), with a final measurement completed at the 9 month study time point (post intervention).
An intravenous line will be placed to draw serial serum and plasma samples prior to (time 0), and again 30, 60, 120, 180, minutes and 24, and 48 hours following an acute session of either an EAW + sham tSCS or an EAW + active tSCS training intervention depending on that participant's group assignment.
Obtained prior to starting the study at enrollment (baseline), at the 4.5 month study time point (mid-point), with a final measurement completed at the 9 month study time point (post intervention).
Seated and Supine Electromyography (EMG) assessments of Muscle Activation
Time Frame: Obtained prior to starting the study at enrollment (baseline), at the 4.5 month study time point (mid-point), with a final measurement completed at the 9 month study time point (post intervention).
Surface EMG data will be collected from muscles in each leg to assess surface EMG amplitudes of these muscles during attempts at volitional knee extension and flexion and ankle plantar- and dorsi-flexion using surface sensors. Furthermore, the resting EMG protocol will be performed to determine the individualized mapping to determine the minimum tSCS intensity required to evoke a motor evoked potential (MEP).
Obtained prior to starting the study at enrollment (baseline), at the 4.5 month study time point (mid-point), with a final measurement completed at the 9 month study time point (post intervention).

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.
VA Office of Research and Development

Investigators

Investigators

A researcher involved in a clinical study. Related terms include site principal investigator, site sub-investigator, study chair, study director, and study principal investigator.
  • Principal Investigator: Chris Cirnigliaro, MS, James J. Peters Veterans Affairs 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 (Estimated)

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.
November 1, 2026

Primary Completion (Estimated)

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.
November 1, 2030

Study Completion (Estimated)

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.
November 1, 2032

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).
February 10, 2026

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.
February 10, 2026

First Posted (Actual)

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.
February 18, 2026

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.
July 22, 2026

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.
July 20, 2026

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.
July 1, 2026

More Information

Terms related to this study

Keywords

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.
  • RRD8-002-25M
  • 1IK2RD000484-01A1 (U.S. NIH Grant/Contract: RRD&T)

Plan for Individual participant data (IPD)

Plan to Share Individual Participant Data (IPD)?

NO

Drug and device information, study documents

Studies a U.S. FDA-regulated drug product

No

Studies a U.S. FDA-regulated device product

Yes

product manufactured in and exported from the U.S.

No

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.

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