Neuromodulation Techniques After SCI

• ClinicalTrials.gov Identifier: NCT04241250
• Recruitment Status: Recruiting
• First Posted: January 27, 2020
• Last Update Posted: March 13, 2023
• Sponsor: VA Office of Research and Development
• Collaborator: Virginia Commonwealth University
• Information provided by (Responsible Party): VA Office of Research and Development

Study Description

Brief Summary:

Spinal cord injury (SCI) leads to several health-related consequences often linked to reduced levels of physical activity. Direct stimulation of the spinal cord, either through implanted devices or surface stimulation, has been combined with intense physical therapy assisted treadmill walking to facilitate independent standing and stepping. These current methods require 3-4 highly skilled therapists and may not be feasible in all rehabilitation settings, especially when considering the growing number of SCI patients each year. Therefore, the use of robotic exoskeleton suits combined with direct stimulation of the spinal cord (requiring 1-2 therapists) may offer an alternative rehabilitation approach to overcome their limited abilities to stand and walk. Such improvements may also help to reverse or eliminate other health-related consequences associated with SCI. The pilot work will provide the preliminary evidence required to design future clinical trials for Veterans and civilians with SCI to restore overground mobility.

Condition or disease	Intervention/treatment	Phase
Spinal Cord Injury	Device: EAW+SCES (exoskelton and spinal cord epidural stimulation); Device: EAW+TS (exoskelton and transspinal stimulation)	Phase 2

Detailed Description:

Restoring locomotion following spinal cord injury (SCI) has been the focus of years of research aimed at ameliorating several of health-related comorbidities. Spinal cord epidural stimulation (SCES) exhibits the rehabilitation potential of restoring locomotion in individuals with SCI when combined with intensive locomotion training. Despite this potential, such protocols are likely impractical when applied across large clinical SCI populations due to high monetary costs. Similar to SCES, transspinal stimulation (TS) has also exhibited neuromodulatory benefits by externally stimulating lumbro-sacral neural circuity to generate step-like activities in persons with complete SCI; however, these techniques also require intense gait training. Recently robotic exoskeletons have been used as a promising tool to circumvent limitations associated with labor-intensive locomotor training, and have been safely used as an effective approach in improving levels of physical activity in persons with complete SCI.

Recent work has demonstrated the benefits of combining EAW and neuromodulatory techniques. Following 12-weeks of EAW+SCES training, improvements in locomotion led researchers to decrease the amount of EAW swing assistance to 35% in a person with a C7 complete SCI. This was accompanied by 573 unassisted steps, which represents 50% of the total number of steps taken during that session. Electromyographic (EMG) activity also increased during both stance and swing phases, reflecting the individual's ability to rhythmically fire paralyzed muscles during EAW+SCES. Additionally, cardio-metabolic loads were increased during exoskeletal stepping when combined with SCES as compared to stepping without SCES. The participant also showed a modest decrease in his total and regional absolute fat mass. These preliminary findings suggest that neuromodulation using SCES with exoskeletal ambulation may provide a feasible rehabilitation approach for persons with SCI. The goal of the current study is to examine and compare the effects of EAW combined with SCES or TS in persons with motor complete SCI. The data generated from this application will also enable larger clinal trials to explore ways to optimize exoskeletal assisted gait training through the use of different neuromodulation modalities with SCI.

Following a repeated-measure design, 10 participants with chronic, motor complete (AIS A and B) SCI (age:18-60 years) will be randomly assigned to participate in either 6-months of EAW+SCES (n=5) or EAW+TS (n=5) training. The entire duration of the trial will be approximately 1 year for each participant. Initially, participants will undergo 3-months of EAW training (3 sessions/week), which will be followed by randomization into either a EAW+SCES group or EAW+TS group for an additional 6-months of training (both groups: 3 sessions/week) and a 3-month follow-up period for both groups. Measurements at baseline (BL: prior to EAW) and 4 post-intervention timepoints will occur every 3-months (P1: following 3-months of EAW; P2: following 3-months of EAW+TS or EAW+SCES; P3: after completing 6-months of EAW+TS or EAW+SCES; P4: 3-months after termination of EAW+TS or EAW+SCES).

This pilot work will have 3 specific aims: Aim 1. The investigators will determine and compare improvements to locomotor control following 6 months of EAW+TS and EAW+SCES as measured by 10-meter walking speed, the number of unassisted EAW steps, and EMG activity.

Aim 2. The investigators will determine and compare improvements to cardio-metabolic risk factors following 6 months of EAW+TS and EAW+SCES as measured by total and regional body composition, oxygen uptake, and fasting lipid profile.

Aim 3. The investigators will determine and compare improvements in bladder health following 6 months of EAW+TS and EAW+SCES as measured by bladder filling and emptying

Study Design

• Study Type: Interventional (Clinical Trial)
• Estimated Enrollment: 10 participants
• Allocation: Randomized
• Intervention Model: Parallel Assignment
• Intervention Model Description: Exoskeletal assisted walking and spinal cord epidural stimulation (EAW+SCES) Exoskeletal assisted walking and Transspinal stimulation (EAW+TS)
• Masking: None (Open Label)
• Primary Purpose: Health Services Research
• Official Title: Transspinal Versus Epidural Stimulation for Exoskeletal Assisted Walking After Spinal Cord Injury
• Actual Study Start Date: June 1, 2020
• Estimated Primary Completion Date: June 30, 2023
• Estimated Study Completion Date: December 30, 2023

Arms and Interventions

Arm	Intervention/treatment
Experimental: EAW+SCES; Three months of exoskeleton training followed by 6 months of epidural stimulation.	Device: EAW+SCES (exoskelton and spinal cord epidural stimulation); Three months of exoskeleton training followed by 6 months of epidural stimulation.
Experimental: EAW+TS; Three months of exoskeleton training followed by 6 months of transspinal stimulation.	Device: EAW+TS (exoskelton and transspinal stimulation); Three months of exoskeleton training followed by 6 months of transspinal stimulation.

Outcome Measures

Primary Outcome Measures :

1. 10-meter walking speed (m/sec) [ Time Frame: 9 months ]
   After fitted in the robotic exoskeleton, the participant will be asked to walk for 10-meter distance and the time and speed will be determined.
2. Muscles electromyography (EMG) activity (micro-volts) [ Time Frame: 9 months ]
   EMG activity will measure electrical activity from 12 leg muscles of hip, knee, and ankle joints during locomotion

Secondary Outcome Measures :

1. Fat mass and fat-free mass (kg) [ Time Frame: 9 months ]
   Body composition will be captured using dual energy x-ray absorptiometry (DXA) to measure fat mass (kg) and fat-free mass (kg) every 3 months during the course of the trial.
2. Oxygen Uptake (ml/min) [ Time Frame: 9 months ]
   Oxygen uptake during resting, standing and walking will be measured during 6 minutes walking test every 3 months during the course of the trial.
3. Fasting lipid profile (mg/dl) [ Time Frame: 9 months ]
   After overnight fast, blood will be drawn to measure your circulating triglycerides, low and high density lipoproteins and cholesterol.

Other Outcome Measures:

1. Volume of bladder Capacity during filling and voiding (ml) [ Time Frame: 9 months ]
   A multichannel urodynamics system (Laborie) will be used to perform urodynamic studies . A urethral catheter will be placed, and saline is infused into the bladder. A pressure transducer is also inserted into the bladder and records pressure during filling. We will then measure the volume of the bladder during filling and during emptying.

Eligibility Criteria

• Ages Eligible for Study: 18 Years to 70 Years (Adult, Older Adult)
• Sexes Eligible for Study: Male
• Accepts Healthy Volunteers: No

Criteria

Inclusion Criteria:

• All participants will be between 18-70 years old, male, with traumatic motor complete SCI and level of injury of T10 and above, as determined by EMG testing and International Standards for Neurological Classification of SCI (ISNCSCI) exam
• All participants will undergo ISNCSCI examination for neurological level and function and only those with American Spinal Injury Classification (AIS A and B; i.e. motor deficit below the level of injury) will be included

Exclusion Criteria:

Participants with any of the following pre-existing medical conditions will be excluded from the current trial:

• Diagnosis of neurological injury other than SCI, including cauda equina or distal conus injuries resulting in limb or sacral areflexia
• Unhealed fracture in either lower or upper extremities
• Severe scoliosis, hip knee range of motion (ROM) or flexion knee contractures preventing positioning in an exoskeleton or plantarflexion contracture greater than 20 degrees
• Untreated or uncontrolled hypertension defined as high resting blood pressure greater than 140/90 mmHg and severe orthostatic hypotension (drop greater than 20 mmHg compared to resting supine blood pressure) or incapable to maintain a sitting or EAW standing posture
• Other medical conditions including cardiovascular disease, uncontrolled type II DM, uncontrolled hypertension, and those on insulin, pressures sores stage 3 or greater, or symptomatic urinary tract infection
• Unable to fit in the device for any reason
• Taking anti-coagulants or anti-platelet agents, including aspirin if unable to be off this medication for medical reasons
• Implanted pacemakers and/or implanted defibrillator devices
• DXA T-Score less than -2.5. Scans done will include total body, dual hips and knees. Total hip BMD T-scores < -3.5 and knee BMD scores of less than 0.6 g/cm2

• Functional upper and lower extremity ROM, strength, spasticity and skin integrity will also have assessed prior to enrollment in the program.

  • The Modified Ashworth Scale will be used to ensure safety of the participants prior to engagement in the rehabilitation program

    • Participants with severe spasticity or limited ROM will be excluded from the trial
    • This is based on the Ekso manufacturer's recommendations
• Untreatable severe spasticity judged to be contraindicated by the site Physician
• Pressure ulcer of the trunk, pelvic area, or lower extremities of grade 3 or more
• Psychopathology documentation in the medical record or history that may conflict with study objectives
• Any condition that, in the judgment of the principal investigator or medical provider, precludes safe participation in the study and/or increases the risk of infection

Contacts and Locations

Contacts

Contact: Ashraf Gorgey, PhD PT; (804) 675-5000 ext 3386; ashraf.gorgey@va.gov

Contact: Robert Trainer, MD; (804) 675-5110; robert.trainer@va.gov

Locations

United States, Virginia

Hunter Holmes McGuire VA Medical Center, Richmond, VA; Recruiting

Richmond, Virginia, United States, 23249

Contact: William F Maragos, MD PhD 804-675-5127 William.Maragos@va.gov

Contact: Robert C Dresch (804) 675-5151 robert.dresch@va.gov

Principal Investigator: Ashraf Gorgey, PhD PT

Sponsors and Collaborators

VA Office of Research and Development

Virginia Commonwealth University

Investigators

• Principal Investigator: Ashraf Gorgey, PhD PT; Hunter Holmes McGuire VA Medical Center, Richmond, VA

More Information

• Responsible Party: VA Office of Research and Development
• ClinicalTrials.gov Identifier: NCT04241250
• Other Study ID Numbers: B3456-P
• First Posted: January 27, 2020
• Last Update Posted: March 13, 2023
• Last Verified: March 2023

Individual Participant Data (IPD) Sharing Statement:

• Plan to Share IPD: No

• Studies a U.S. FDA-regulated Drug Product: No
• Studies a U.S. FDA-regulated Device Product: Yes
• Device Product Not Approved or Cleared by U.S. FDA: Yes
• Product Manufactured in and Exported from the U.S.: Yes

Keywords provided by VA Office of Research and Development:

Robotic Exoskeleton; Epidural Stimulation; Transspinal stimulation; Spinal cord injury; Rehabilitation

Additional relevant MeSH terms:

Spinal Cord Injuries; Wounds and Injuries; Spinal Cord Diseases; Central Nervous System Diseases; Nervous System Diseases; Trauma, Nervous System