The Effect of Exoskeletal-assisted Walking Combined With Transcutaneous Spinal Cord Stimulation on Bone Strength.

January 6, 2026 updated by: Christopher M. Cirnigliaro, Bronx VA Medical Center

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

Not yet recruiting

Conditions

Intervention / Treatment

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

Interventional

Enrollment (Estimated)

24

Phase

  • 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 Backup

Study Locations

  • United States
    • New Jersey
      • West Orange, New Jersey, United States, 07052
        • Kessler Foundation
        • Principal Investigator:
          • Gail F Forrest, PhD
        • Contact:
        • Contact:
        • Principal Investigator:
          • Christopher M Cirnigliaro, Ph.D.
        • Sub-Investigator:
          • Christopher P Cardozo, Ph.D.
        • Sub-Investigator:
          • Noam Y Harel, M.D.

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

Ages Eligible for Study

  • Adult

Accepts Healthy Volunteers

No

Description

  • Participant Screening:

    1. International Standards for Neurological Classification of Spinal Cord Injury (ISNCSCI) neurological assessment examination to determine the level and completeness of SCI when participants screen for entry into the study. The ISNCSCI exam will be performed by the study physician using a tool that assesses sensory function (light touch and pinprick) in each dermatome (A dermatome is an area of skin that sends touch, pain, temperature, and other sensory signals back to the brain) and motor function (motor function is a general term to describe the way muscles create movement) in ten key muscles. This test will determine the level of SCI, defined as the lowest spinal level with normal function, and assigns a classification of severity according to the ISNCSCI scale. In this study, both ISNCSCI grade C and grade D would make a participant eligible for this study.
    2. DXA study to assess bone mineral density (BMD) at the total hip (TH), distal femur (DF), and proximal tibia (PT) that will be compared to the cutoff values described in the exclusion criteria section.
    3. Medical history and exam to ensure medical health, anthropometric compatibility for EAW, and to identify fragility or traumatic fractures, unhealed fractures, and signs of swelling, bruising, and discoloration of the legs.

  • Inclusion Criteria:

    1. Between the ages of 21-60 years old
    2. Non-walkers with an SCI greater than 3 years post injury.
    3. 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.
    4. Neurologic level of injury as determined by study staff between C5-T10 (completed at participant's screening).
    5. Capable of gripping Lofstrand crutches and/or a walker without assistance.
    6. Wheelchair reliant 100% of the time.
    7. Height is between 62 inches and 74 inches.
    8. Weight less than 220lbs.

    9. 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:

    1. 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.
    2. Current bone disease diagnosis (e.g., osteomyelitis, hyperparathyroidism)
    3. 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
    4. 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.
    5. Currently in a gym/rehabilitation program performing ambulatory interventions such as EAW, as determined by the study staff.
    6. Currently prescribed any medications that can affect muscle and/or bone metabolism, as determined by the study staff.

Exclusion Criteria from MRI Safety Screening:

  1. Medically unsafe to receive an MRI scan.
  2. Claustrophobia
  3. Baclofen pump

  4. 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
Intervention / Treatment
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) + active Transcutaneous Spinal Cord Stimulation (tSCS)
The full electrical signal is delivered during lumbosacaral tSCS treatment while simultaneously performing EAW. Participants in both groups will receive 60 minutes of EAW + active tSCS overground training per session for a total of 108 sessions (3 X week for 36 weeks).
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) + 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

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 after 9 months of participating in the study interventions.
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 after 9 months of participating in the study interventions.

Other Outcome Measures

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), after ~54 training sessions (4.5 months), with a final measurement completed after 9 months of the training interventions.
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), after ~54 training sessions (4.5 months), with a final measurement completed after 9 months of the training interventions.
Muscle and Bone Serum and Plasma Biomarker Time-Course Response
Time Frame: Obtained prior to starting the study at enrollment (baseline), after ~54 training sessions (4.5 months), with a final measurement completed after 9 months of the training interventions.
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), after ~54 training sessions (4.5 months), with a final measurement completed after 9 months of the training interventions.
Seated and Supine Electromyography (EMG) assessments of Muscle Activation
Time Frame: Obtained prior to starting the study at enrollment (baseline), after ~54 training sessions (4.5 months), with a final measurement completed after 9 months of the training interventions.
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), after ~54 training sessions (4.5 months), with a final measurement completed after 9 months of the training interventions.

Collaborators and Investigators

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

Sponsor

Bronx VA Medical Center

Collaborators

Kessler Foundation

Investigators

  • Study Director: Christopher P Cardozo, M.D., James J. Peters 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 (Estimated)

July 1, 2026

Primary Completion (Estimated)

June 30, 2031

Study Completion (Estimated)

June 1, 2033

Study Registration Dates

First Submitted

December 18, 2025

First Submitted That Met QC Criteria

January 6, 2026

First Posted (Actual)

January 8, 2026

Study Record Updates

Last Update Posted (Actual)

January 8, 2026

Last Update Submitted That Met QC Criteria

January 6, 2026

Last Verified

January 1, 2026

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

  • 1914010-2
  • IK2 RD000484-01A1 (Other Grant/Funding Number: Department of Veterans Affairs Rehabilitation Research, and Development Translation)

Plan for Individual participant data (IPD)

Plan to Share Individual Participant Data (IPD)?

NO

IPD Plan Description

At this time, the investigators must declare that IPD will not be shared with other investigators, as the VA has not approved a plan and is currently not in place at our VA research laboratory. The investigators anticipate a policy will be approved over the next 24 months to share IPD with other investigators. Once an approved plan is in place, it will be added to the study protocol and the PRS site for this trial.

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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