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Motor and Autonomic Concomitant Health Improvements With Neuromodulation and Exoskeleton Training: A RCT in Individuals With SCI (MACHINE)

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ClinicalTrials.gov Identifier: NCT04726059
Recruitment Status : Not yet recruiting
First Posted : January 27, 2021
Last Update Posted : April 27, 2021
Sponsor:
Collaborator:
Praxis Spinal Cord Institute
Information provided by (Responsible Party):
Andrei Krassioukov, University of British Columbia

Brief Summary:
Spinal cord injury (SCI) disrupts many aspects of life, including the loss of volitional movement and involuntary control of bodily functions; both crucial functional recovery priorities for this population. Mobility impairments and secondary complications limit an individual's ability to exercise, a behavior known to have wide-ranging functional and health benefits. This trial will investigate whether activity-based therapy (ABT), using a robotic exoskeleton, can change the strength of signals from the brain that control volitional movement, leading to improvements in standing and seated balance as well as other important involuntary bodily (i.e. cardiovascular, urinary tract, bowel and sexual) functions. The investigators aim to determine whether these improvements can be augmented with the addition of non-invasive transcutaneous spinal cord stimulation (TCSCS). This therapy has been shown to re-awaken dormant spinal circuits. In this randomized controlled trial, TCSCS with ABT, using robotic-assisted gait training (three sessions/week for twelve weeks), will be compared to ABT+SHAM in individuals with chronic motor-complete spinal cord injury (SCI). Those in the ABT+SHAM group will be given the option to complete an ABT+TCSCS open-label follow-up. Before and after training, the following outcomes will be assessed by validated methods: corticospinal excitability, motor function, and seated and standing balance (Hypothesis 1 - Motor Function); severity and frequency of blood pressure instability, urinary tract, bowel, and sexual dysfunctions (Hypothesis 2 - Autonomic Functions); and general health (Hypothesis 3 - Quality of Life). This collaborative project is between consumers with SCI and clinicians/scientists with expertise in SCI care (kinesiologists, physiotherapists, physiatrists, sexual health clinicians). Compared to ABT alone, the investigators anticipate that ABT+TCSCS will result in superior improvements in motor and autonomic functions in individuals with SCI.

Condition or disease Intervention/treatment Phase
Spinal Cord Injuries Neurogenic Bladder Neurogenic Bowel Device: Transcutaneous Spinal Cord Stimulation Device: SHAM (low-intensity) Transcutaneous Spinal Cord Stimulation Device: Activity-Based Therapy Not Applicable

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Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 12 participants
Allocation: Randomized
Intervention Model: Parallel Assignment
Intervention Model Description: Participants are assigned to either an ABT+TCSCS or ABT+SHAM arm. Participants who are assigned to ABT+SHAM will have the opportunity to complete an ABT+TCSCS open-label follow-up.
Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
Primary Purpose: Treatment
Official Title: Motor and Autonomic Concomitant Health Improvements With Neuromodulation and Exoskeleton (MACHINE) Training: A Randomized Controlled Trial in Individuals With SCI
Estimated Study Start Date : June 2021
Estimated Primary Completion Date : December 2023
Estimated Study Completion Date : December 2023

Arm Intervention/treatment
Sham Comparator: ABT+SHAM
The SHAM is low-intensity, ineffective stimulation verified by the absence of lower extremity skeletal muscle activation and delivered at the same anatomical location as TCSCS.
Device: SHAM (low-intensity) Transcutaneous Spinal Cord Stimulation
Ineffective stimulation will be verified by the absence of lower extremity skeletal muscle activation, determined by electromyography, and administered at the same anatomical location as therapeutic TCSCS.

Device: Activity-Based Therapy

Using the Lokomat exoskeleton by Hocoma, all participants (both arms) will train 3 times per week for 12 weeks with a target to reach 20 minutes of balance training and 30 minutes of gait training in each session.

For balance training, participants will be asked to attempt to stand to the best of their ability without relying on the Lokomat's structural support. Sensors built into the Lokomat will capture pressure the participant is applying to the joints and provide visual feedback for how much they are relying on the device for support. Will be done in 5-minute bouts with 1-minute rest inbetween.

For gait training, the Lokomat will provide participants with the complete walking assistance, but level of body weight support and speed of walking will be adjusted to allow the person to bear as much weight as possible while maintaining proper stance limb kinematics.

Other Name: Lokomat (Hocoma)

Experimental: ABT+TCSCS
Therapeutic TCSCS will be delivered during ABT using an isolated bipolar constant current stimulator. Continuous TCSCS applied over the T11-T12 spinous processes at 5-40 Hz has been shown to induce stepping movements in participants with their legs in a gravity-independent position.
Device: Transcutaneous Spinal Cord Stimulation
Therapeutic TCSCS will be delivered during ABT using an isolated bipolar constant current stimulator (Keypoint 4, Natus Medical Incorporated, USA). A biphasic rectangular waveform with 0.3 to 1.0-ms pulses, a carrier frequency of 10 kHz, administered at 5 to 40 Hz with a current ranging from 30 to 200 mA will be used.

Device: Activity-Based Therapy

Using the Lokomat exoskeleton by Hocoma, all participants (both arms) will train 3 times per week for 12 weeks with a target to reach 20 minutes of balance training and 30 minutes of gait training in each session.

For balance training, participants will be asked to attempt to stand to the best of their ability without relying on the Lokomat's structural support. Sensors built into the Lokomat will capture pressure the participant is applying to the joints and provide visual feedback for how much they are relying on the device for support. Will be done in 5-minute bouts with 1-minute rest inbetween.

For gait training, the Lokomat will provide participants with the complete walking assistance, but level of body weight support and speed of walking will be adjusted to allow the person to bear as much weight as possible while maintaining proper stance limb kinematics.

Other Name: Lokomat (Hocoma)




Primary Outcome Measures :
  1. Change in corticospinal excitability [ Time Frame: Weeks 2 and 14 ]
    Corticospinal excitability is measured by recording motor evoked potentials to plot a slope that will provide an index score.

  2. Change in attempted voluntary contraction [ Time Frame: Weeks 2 and 14 ]
    Attempted voluntary contraction will be completed in the following muscles: rectus abdominis, pelvic floor muscles, vastus lateralis, biceps femoris, tibialis anterior, and soleus. The mean electromyography amplitude from each muscle during rest and an attempted contraction will be calculated.

  3. Change in seated and standing balance control [ Time Frame: Weeks 2 and 14 ]
    Balance control will be measured using force plate sensors embedded within the Lokomat while seated and standing.


Secondary Outcome Measures :
  1. Change in blood pressure variability [ Time Frame: Weeks 2 and 14 ]
    Blood pressure variability will be measured using a 24 hour ambulatory blood pressure monitor which records the blood pressure every 15 minutes during the daytime period, and then every hour during the night-time period.

  2. Change in cardiac outcomes [ Time Frame: Weeks 2 and 14 ]
    Cardiac outcomes will be measured using echocardiogram. The echocardiogram images will be collected using parasternal long and short axis, apical 4, 2 and 3 chamber, and subcostal views.

  3. Change in dysautonomia [ Time Frame: Weeks 2 and 14 ]
    Dysautonomia will be measured using a 60-degree head-up tilt table test where the participant's blood pressure will be measured at supine rest for 10 minutes, and then at approximately 60° upright stand position for 15 minutes.

  4. Change in autonomic dysreflexia based on the autonomic dysreflexia following spinal cord injury questionnaire [ Time Frame: Weeks 2 and 14 ]
    Autonomic dysreflexia following spinal cord injury questionnaire assesses self-reported frequency and severity of autonomic related symptoms. The participant will complete 18 items from the third and fourth part of the questionnaire only, which evaluates autonomic dysfunction and hypotension.

  5. Change in bladder function based on the neurogenic bladder symptom score [ Time Frame: Weeks 2 and 14 ]
    Neurogenic bladder symptom score comprises 23 questions covering 3 domains, including incontinence, storage & voiding, and specific consequences, as well as one question on QoL.

  6. Change in bladder function based on the incontinence - quality of life questionnaire [ Time Frame: Weeks 2 and 14 ]
    Incontinence - Quality of life questionnaire comprises 10 questions covering 3 domains, including avoidance and limiting behaviour, psychosocial impacts, and social embarrassment, which will be summarised as a total score.

  7. Change in bowel function based on the neurogenic bowel dysfunction score [ Time Frame: Weeks 2 and 14 ]
    Neurogenic bowel dysfunction score comprises 10 questions focusing on defecation (i.e., frequency, duration, and clinical symptoms), constipation (i.e., use of aiding medication and digital stimulation), fecal incontinence (i.e., frequency, aiding medication, and flatus; and peri-anal skin problems.

  8. Change in sexual function based on the international index of erectile function questionnaire [ Time Frame: Weeks 2 and 14 ]
    International index of erectile function questionnaire comprises of 15 questions covering five domains, including erectile function, orgasmic function, intercourse satisfaction, and overall satisfaction. Only males will complete the international index of erectile function questionnaire.

  9. Change in sexual function based on the female sexual function index [ Time Frame: Weeks 2 and 14 ]
    Female sexual function index comprises of 19 questions covering six domains, including desire, arousal, lubrication, orgasm, satisfaction, and pain. Only females will complete the female sexual function index.

  10. Change in quality of life based on the short form (SF-36) health survey [ Time Frame: Weeks 2 and 14 ]
    Short form (SF-36) health survey consists of 8 domains pertaining to the participants' experiences in the last 4 weeks. Each of the 8 summed scores is linearly transformed onto a scale from 0 (negative health) to 100 (positive health) to provide a score for each subscale.

  11. Change in quality of life based on fatigue severity scale [ Time Frame: Weeks 2 and 14 ]
    Fatigue severity scale is a 9-item questionnaire, which captures how fatigue interferes with certain activities of daily living and is accompanied by a global fatigue visual analogue scale.

  12. Change in quality of life based on spinal cord injury: spasticity evaluation tool [ Time Frame: Weeks 2 and 14 ]
    Spinal cord injury: spasticity evaluation tool is a thorough subjective assessment tool that asks the participant a total of 35 questions regarding both the problematic and useful effects of spasticity on daily life in the past 7 days.



Information from the National Library of Medicine

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Ages Eligible for Study:   18 Years to 60 Years   (Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
Criteria

A participant must meet all of the following criteria in order to be eligible for inclusion:

  • Resident of British Columbia, Canada with active provincial medical services plan
  • Male or female, 18-60 years of age
  • Chronic traumatic SCI (non-progressive, with complete motor paralysis) at or above the T6 spinal segment
  • At least 1-year post injury, at least 6 months from any spinal surgery
  • American Spinal Injury Association Impairment Scale (AIS) A, B
  • Able to tolerate an upright posture for 30 minutes (with or without breaks)
  • Willing and able to comply with all clinic visits and study-related procedures
  • Able to understand and complete study-related questionnaires (must be able to understand and speak English or have access to an appropriate interpreter as judged by the investigator)
  • No painful musculoskeletal dysfunction, unhealed fracture, pressure sore, or active infection that may interfere with testing activities
  • Stable management of spinal cord related clinical issues (i.e., spasticity management)
  • Women of childbearing potential must not be intending to become pregnant, currently pregnant, or lactating. The following conditions apply:

    1. Women of childbearing potential must have a confirmed negative pregnancy test prior to the baseline visit. During the trial, all women of childbearing potential will undergo urine pregnancy tests at their monthly clinic visits as outlined in the schedule of events
    2. Women of childbearing potential must agree to use adequate contraception during the period of the trial and for at least 28 days after completion of treatment. Effective contraception includes abstinence
  • Sexually active males with female partners of childbearing potential must agree to use effective contraception during the period of the trial and for at least 28 days after completion of treatment
  • Must provide informed consent

A participant who meets any of the following criteria will be ineligible to participate:

  • Ventilator dependent
  • Clinically significant, unmanaged, depression (PHQ-9 above 15) or ongoing drug abuse
  • Use of any medication or treatment that in the opinion of the investigator indicates that it is not in the best interest of the participant to participate in this study
  • Intrathecal baclofen pump
  • Cardiovascular, respiratory, bladder, or renal disease unrelated to SCI or presence of hydronephrosis or presence of obstructive renal stones
  • Presence of severe acute medical issue that in the investigator's judgement would adversely affect the participant's participation in the study. Examples include, but are not limited to acute urinary tract infections, active heterotopic ossification, newly changed antidepressant medications [tricyclics], debilitating muscle pain, pressure sores, or unstable diabetes
  • Any implanted metal (other than dental implants) in the skull or presence of pacemakers, stimulators, or medication pumps in the trunk
  • History of osteoporosis, low bone mineral density, or fragility fractures in the lower limbs
  • History of seizures/epilepsy or recurring headaches
  • Poor range of motion,severe spasticity, or contractures in the legs that prevents use of the Lokomat
  • Weight greater than 136 kg, height less than 1.58m, or height greater than 1.88m (limits of the Lokomat)
  • Severe anemia (Hgb<8 g/dl) or hypovolemia as measured by hematocrit via blood test in the last six months
  • Participant is a member of the investigational team or his /her immediate family
  • Participant has undergone electrode implantation surgery

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT04726059


Contacts
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Contact: Carolyn Barakso 604-675-8816 barakso@icord.org

Sponsors and Collaborators
University of British Columbia
Praxis Spinal Cord Institute
Investigators
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Principal Investigator: Andrei Krassioukov, MD, PhD, FRCPC University of British Columbia
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Responsible Party: Andrei Krassioukov, Principal Investigator, University of British Columbia
ClinicalTrials.gov Identifier: NCT04726059    
Other Study ID Numbers: H20-01307
First Posted: January 27, 2021    Key Record Dates
Last Update Posted: April 27, 2021
Last Verified: April 2021

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Studies a U.S. FDA-regulated Drug Product: No
Studies a U.S. FDA-regulated Device Product: No
Keywords provided by Andrei Krassioukov, University of British Columbia:
Activity-based Therapy
Spinal Cord Stimulation
Transcutaneous Spinal Cord Stimulation
Additional relevant MeSH terms:
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Neurogenic Bowel
Spinal Cord Injuries
Urinary Bladder, Neurogenic
Spinal Cord Diseases
Central Nervous System Diseases
Nervous System Diseases
Trauma, Nervous System
Wounds and Injuries
Neurologic Manifestations
Urinary Bladder Diseases
Urologic Diseases
Colonic Diseases, Functional
Colonic Diseases
Intestinal Diseases
Gastrointestinal Diseases
Digestive System Diseases