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

Bronx VA Medical Center

Status: Begins enrollment in 4 months

Conditions: Sarcopenia; Secondary Osteoporosis

Treatments: Device: Exoskeleton-Assisted Walking (EAW) + active Transcutaneous Spinal Cord Stimulation (tSCS); Device: Exoskeleton-assisted walking (EAW) + sham Transcutaneous Spinal Cord Stimulation (tSCS)

Study type: Interventional

Funder types: Other; Other U.S. Federal agency

Identifiers

NCT07325149

IK2 RD000484-01A1 (Other Grant/Funding Number)

1914010-2

Details and patient eligibility

About

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.

Full 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.

Enrollment: 24 estimated patients

Sex: All

Ages: 21 to 60 years old

Volunteers: No Healthy Volunteers

Inclusion and exclusion criteria

• 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

Trial design

Primary purpose: Treatment

Allocation: Randomized

Interventional model: Parallel Assignment

Masking: None (Open label)

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24 participants in 2 patient groups

Exoskeleton-Assisted Walking (EAW) + active Transcutaneous Spinal Cord Stimulation (tSCS)

Experimental group

Description:

The EAW + active tSCS group will receive simultaneous lumbosacral tSCS while simultaneously performing EAW.

Treatment:

Device: Exoskeleton-Assisted Walking (EAW) + active Transcutaneous Spinal Cord Stimulation (tSCS)

Exoskeleton-assisted walking (EAW) + sham Transcutaneous Spinal Cord Stimulation (tSCS)

Sham Comparator group

Description:

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).

Treatment:

Device: Exoskeleton-assisted walking (EAW) + sham Transcutaneous Spinal Cord Stimulation (tSCS)