Motor & Autonomic Concomitant Health Improvements With Neuromodulation & Exercise Training: An SCI RCT

NCT04726059 | Recruiting DMC

• 1 other identifier: H20-01307
• Study Type: interventional
• Target: 12
• Locations: 1 country
• Sites: 1

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 body-weight-supported treadmill training (BWSTT), can change the strength of signals from the brain that control volitional movement, leading to improvements in 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 (TSCS). This therapy has been shown to re-awaken dormant spinal circuits. In this randomized controlled trial, TSCS with ABT, using BWSTT (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+TSCS open-label follow-up. Before and after training, the following outcomes will be assessed by validated methods: corticospinal excitability, motor function, and seated 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+TSCS will result in superior improvements in motor and autonomic functions in individuals with SCI.

Conditions

Spinal Cord Injuries; Neurogenic Bladder; Neurogenic Bowel

Keywords

Activity-based Therapy; Spinal Cord Stimulation; Transcutaneous Spinal Cord Stimulation

Outcome Measures

Primary Outcomes (4)

• Change in attempted voluntary motor activation (supine)

  While lying in the supine position, the following voluntary motor contractions will be attempted: trunk flexion, hip flexion, knee flexion, knee extension, ankle dorsiflexion, and ankle plantar flexion. Surface EMG recordings will be taken from the rectus abdominis, rectus femoris, biceps femoris, vastus lateralis, tibialis anterior, soleus, and gastrocnemius. The root mean square (RMS) EMG amplitude from each muscle during rest and the attempted contraction for each participant and each trial will be calculated to explore presence of muscle activity in each movement.

  Weeks 2 and 14

• Change in attempted voluntary motor activation (walking)

  Participants will attempt to voluntarily activate lower limb muscles while walking in the body-weight-supported treadmill system. Surface EMG recordings will be taken from the rectus femoris, biceps femoris, vastus lateralis, tibialis anterior, soleus, and gastrocnemius. The root mean square (RMS) EMG amplitude from each muscle during rest and stepping for each participant and each trial will be calculated to explore presence of muscle activity during walking.

  Weeks 2 and 14

• Change in lower limb proprioceptive sense

  Lower limb proprioceptive sense will be quantified using previously validated assessments of joint position sense and movement detection sense using custom software of the Lokomat. Kinesthesia and joint position sense will be determined.

  Weeks 2 and 14

• Change in blood pressure regulation

  Blood pressure variability will be measured using a 24-hour ambulatory blood pressure monitor (24-Hr ABPM) which records blood pressure every 15 minutes during the daytime period, and then every hour during the night-time period. Changes in systolic blood pressure will be determined.

  Weeks 2 and 14

Secondary Outcomes (17)

• Change in corticospinal excitability

  Weeks 2 and 14

• Change in spinal excitability

  Weeks 2 and 14

• Change in seated, static balance control

  Weeks 2 and 14

• Change in seated, dynamic balance control

  Weeks 2 and 14

• Change in severity of cardiovascular dysfunction by the ADFSCI

  Weeks 2 and 14

Study Arms (2)

ABT+SHAM

SHAM COMPARATOR

The SHAM is low-intensity, ineffective stimulation delivered at the same anatomical location as TSCS.

Device: SHAM (low-intensity) Transcutaneous Spinal Cord Stimulation; Device: Activity-Based Therapy

ABT+TSCS

EXPERIMENTAL

Therapeutic TSCS will be delivered during ABT using an isolated bipolar constant current stimulator. Continuous TSCS 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; Device: Activity-Based Therapy

Interventions

Transcutaneous Spinal Cord Stimulation DEVICE

Therapeutic TSCS will be delivered during ABT using a non-invasive central nervous system stimulator (TESCoN, SpineX Inc., CA, USA). Stimulation will involve charge balanced monophasic rectangular waveforms with 1.0-ms pulses, administered at 30 Hz, with a carrier frequency of 10 kHz and a current ranging from 10 to 130 mA.

ABT+TSCS

SHAM (low-intensity) Transcutaneous Spinal Cord Stimulation DEVICE

Ineffective stimulation will be administered at the same anatomical location as therapeutic TSCS.

ABT+SHAM

Activity-Based Therapy DEVICE

Using BWSTT, all participants (both arms) will train 3 times per week for 12 weeks with a target to reach 45 minutes of gait training in each session. For gait training, the 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.

ABT+SHAM; ABT+TSCS

Eligibility Criteria

• Age: 18 Years - 60 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64)

You may qualify if:

• 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:
• 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
• 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
• Medication dosage must be stable for period of 4 weeks prior to participation

You may not qualify if:

• 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
• Oral baclofen dose or other anti-spasticity medications greater than 30mg per day
• 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
• Participant has swollen, infected, and inflamed areas or open wounds on the area of stimulation
• 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

Sponsors & Collaborators

• University of British Columbia: lead
• Praxis Spinal Cord Institute: collaborator

Study Sites (1)

Blusson Spinal Cord Centre

Vancouver, British Columbia, V5Z 1M9, Canada

RECRUITING

Related Publications (1)

• Shackleton C, Samejima S, Williams AM, Malik RN, Balthazaar SJ, Alrashidi A, Sachdeva R, Elliott SL, Nightingale TE, Berger MJ, Lam T, Krassioukov AV. Motor and autonomic concomitant health improvements with neuromodulation and exercise (MACHINE) training: a randomised controlled trial in individuals with spinal cord injury. BMJ Open. 2023 Jul 14;13(7):e070544. doi: 10.1136/bmjopen-2022-070544.

  PMID: 37451734 DERIVED

MeSH Terms

Conditions

Spinal Cord Injuries; Urinary Bladder, Neurogenic; Neurogenic Bowel

Condition Hierarchy (Ancestors)

Spinal Cord Diseases; Central Nervous System Diseases; Nervous System Diseases; Trauma, Nervous System; Wounds and Injuries; Neurologic Manifestations; Urinary Bladder Diseases; Urologic Diseases; Female Urogenital Diseases; Female Urogenital Diseases and Pregnancy Complications; Urogenital Diseases; Male Urogenital Diseases; Signs and Symptoms; Pathological Conditions, Signs and Symptoms; Colonic Diseases, Functional; Colonic Diseases; Intestinal Diseases; Gastrointestinal Diseases; Digestive System Diseases

Study Officials

• Andrei Krassioukov, MD,PhD,FRCPC

  University of British Columbia

  PRINCIPAL INVESTIGATOR

Central Study Contacts

Andrea Maharaj, BSc

CONTACT

6046758856; amaharaj@icord.org

Study Design

• Study Type: interventional
• Phase: not applicable
• Allocation: RANDOMIZED
• Masking: SINGLE
• Who Masked: PARTICIPANT
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Principal Investigator

Model Details: Participants are assigned to either an ABT+TSCS or ABT+SHAM arm. Participants who are assigned to ABT+SHAM will have the opportunity to complete an ABT+TSCS open-label follow-up.

Study Record Dates

• First Submitted: January 19, 2021
• First Posted: January 27, 2021
• Study Start: July 22, 2022
• Primary Completion: December 1, 2024
• Study Completion: December 1, 2024
• Last Updated: April 30, 2024

Record last verified: 2024-04

Locations

CA (1)