Non-invasive Spinal Cord Stimulation for Recovery of Autonomic Function After Spinal Cord Injury

NCT05369520 | Recruiting DMC FDA Device

• 2 other identifiers: H22-00365CDMRP-SC210078
• Study Type: interventional
• Target: 30
• Locations: 1 country
• Sites: 2

Brief Summary

This study is a pilot clinical trial to explore the efficacy of transcutaneous spinal cord stimulation (TCSCS) (proof-of-concept) in mitigating crucial autonomic dysfunctions that impact the health-related quality of life of individuals with spinal cord injury (SCI).

Conditions

Spinal Cord Injury; Autonomic Dysfunction; Sexual Dysfunction; Neurogenic Bladder Dysfunction; Neurogenic Bowel Dysfunction; Autonomic Dysreflexia; Orthostatic Hypotension

Keywords

Neurostimulation; Spinal Cord Injury

Outcome Measures

Primary Outcomes (35)

• Targeted TCSCS map modulate resting blood pressure (BP)

  Using continuous beat-by beat BP monitoring via finger photoplethysmography during TCSCS, the researchers will identify the location and stimulation parameters to increase and decrease resting BP. Stimulation site will be either on the thoracic spinal cord (T7-T12) or the lumbosacral spinal cord (L1 - L3). Stimulation will be applied at various frequencies ranging between 1Hz and 90Hz. The outcome is an individualized TCSCS map (i.e. location and stimulation parameters) with change in systolic BP at rest during TCSCS.

  Week 1-2 (once)

• Targeted TCSCS map to activate skeletal muscles and pelvic floor muscles

  Using surface electromyography (EMG), the researchers will identify the motor threshold for skeletal muscles known to be involved in lower urinary tract, bowel and sexual control by delivering TCSCS at various spinal cord segments (T7 to conus medullaris). The outcome is an individualized TCSCS map (i.e. location and stimulation parameters) with pertinent motor thresholds for TCSCS-driven surface EMG.

  Week 1-2 (once)

• Immediate change in BP during the head up tilt test (HUTT)

  During HUTT, participants will be passively moved to approximately 60° upright stand position by the investigators using the tilt table. Using TCSCS to activate spinal sympathetic circuitry and mitigate low resting BP and orthostatic hypotension (OH), and continuous beat-by beat BP monitoring via finger photoplethysmography, researchers will test the safety and efficacy of short-term TCSCS in reproducibly improving OH triggered by HUTT.

  Week 3 - 6 (once)

• Change in BP during the head up tilt test (HUTT) from baseline to after completion of 8 weeks of TCSCS

  Using TCSCS and continuous beat-by beat BP monitoring via finger photoplethysmography, researchers will test the safety and efficacy of long-term TCSCS in improving OH triggered by HUTT.

  Week 15-18 (once)

• Change in BP during the head up tilt test (HUTT) from baseline to 8 weeks after cessation of TCSCS

  Using TCSCS and continuous beat-by beat BP monitoring via finger photoplethysmography, researchers will test the safety and efficacy of long-term TCSCS in improving OH triggered by HUTT after cessation of therapy.

  Week 27-30 (once)

• Immediate change in BP during digital anorectal stimulation (DARS)

  DARS is a routine procedure to initiate a bowel routine. The participant will lay on their right side and DARS will be delivered via an index finger inserted into the rectum, applying gentle pressure for 30-60s. Utilizing TCSCS to inhibit nociceptive afferent and continuous beat-by beat BP monitoring via finger photoplethysmography, researchers will test the safety and efficacy of short-term TCSCS in reproducibly improving autonomic dysreflexia (AD) triggered by DARS.

  Week 3 - 6 (once)

• Change in BP during digital anorectal stimulation (DARS) from baseline to after completion of 8 weeks of TCSCS

  Utilizing TCSCS and continuous beat-by beat BP monitoring via finger photoplethysmography, researchers will test the safety and efficacy of long-term TCSCS in improving AD triggered by DARS.

  Week 15-18 (once)

• Change in BP during digital anorectal stimulation (DARS) from baseline to 8 weeks after cessation of TCSCS

  Utilizing TCSCS and continuous beat-by beat BP monitoring via finger photoplethysmography, researchers will test the safety and efficacy of TCSCS in improving AD triggered by DARS after cessation of therapy.

  Week 27-30 (once)

• Immediate change in rectal pressure measured by anorectal manometry (ARM)

  ARM is well-established methodology that provides a direct assessment of anal sphincter pressure and anorectal coordination during simulated defecation. The test is performed by inserting a catheter, that contains a probe embedded with pressure sensors, through the anus and into the rectum. Researchers will test the safety and efficacy of short-term TCSCS in reproducibly changing average max resting and squeeze pressure (mmHg).

  Week 3 - 6 (once)

• Immediate change in high pressure anal canal zone measured by ARM

  Researchers will test the safety and efficacy of short-term TCSCS in reproducibly changing length of high pressure anal canal zone (cm).

  Week 3 - 6 (once)

• Immediate change in recto-anal inhibitory reflex measured by ARM

  Researchers will test the safety and efficacy of short-term TCSCS in reproducibly changing recto-anal inhibitory reflex.

  Week 3 - 6 (once)

• Immediate change in rectal sensation measured by ARM

  Researchers will test the safety and efficacy of short-term TCSCS in reproducibly changing rectal sensation (mL).

  Week 3 - 6 (once)

• Change in rectal pressure measured by ARM from baseline to after completion of 8 weeks of TCSCS

  Utilizing TCSCS and ARM, researchers will test the safety and efficacy of long-term TCSCS in changing average max resting and squeeze pressure (mmHg).

  Week 15-18 (once)

• Change in high pressure anal canal zone measured by ARM from baseline to after completion of 8 weeks of TCSCS

  Utilizing TCSCS and ARM, researchers will test the safety and efficacy of long-term TCSCS in changing length of high pressure anal canal zone (cm).

  Week 15-18 (once)

• Change in rectal sensation measured by ARM from baseline to after completion of 8 weeks of TCSCS

  Utilizing TCSCS and ARM, researchers will test the safety and efficacy of long-term TCSCS in changing rectal sensation (mL).

  Week 15-18 (once)

• Change in recto-anal inhibitory reflex measured by ARM from baseline to after completion of 8 weeks of TCSCS

  Utilizing TCSCS and ARM, researchers will test the safety and efficacy of long-term TCSCS in changing recto-anal inhibitory reflex.

  Week 15-18 (once)

• Change in rectal pressure measured by anorectal manometry (ARM) from baseline to 8 weeks after cessation of TCSCS

  Utilizing TCSCS and ARM, researchers will test the safety and efficacy of TCSCS in changing average max resting and squeeze pressure (mmHg).

  Week 27-30 (once)

• Change in high pressure anal canal zone measured by anorectal manometry (ARM) from baseline to 8 weeks after cessation of TCSCS

  Utilizing TCSCS and ARM, researchers will test the safety and efficacy of TCSCS in changing length of high pressure anal canal zone (cm).

  Week 27-30 (once)

• Change in recto-anal inhibitory reflex measured by anorectal manometry (ARM) from baseline to 8 weeks after cessation of TCSCS

  Utilizing TCSCS and ARM, researchers will test the safety and efficacy of TCSCS in changing recto-anal inhibitory reflex.

  Week 27-30 (once)

• Change in rectal sensation measured by anorectal manometry (ARM) from baseline to 8 weeks after cessation of TCSCS

  Utilizing TCSCS and ARM, researchers will test the safety and efficacy of TCSCS in changing rectal sensation (mL).

  Week 27-30 (once)

• Immediate change in intravesical pressure at first sensation measured by urodynamic investigation (UDI)

  Standard clinical procedures for UDI, including cystometry with water at 21°C and a filling rate of \< 30 mL per minute through a 6F double lumen catheter with the participants in the supine position, provides a direct assessment of voiding and storage function. Abdominal pressure will be measured with a 10F intrarectal balloon catheter. Filling will be stopped when the participants report a sensation of fullness. Researchers will test the safety and efficacy of short-term TCSCS in reproducibly changing intravesical pressure at first sensation (mmHg).

  Week 3 - 6 (once)

• Immediate change in intravesical pressure at leakage point measured by UDI

  Filling will be stopped at the moment of urine leakage. Researchers will test the safety and efficacy of short-term TCSCS in reproducibly changing intravesical pressure at leakage point (mmHg).

  Week 3 - 6 (once)

• Immediate change in intravesical pressure at maximal volume measured by UDI

  Filling will be stopped at the moment of discomfort/per the request of patient. Researchers will test the safety and efficacy of short-term TCSCS in reproducibly changing intravesical pressure at maximal volume (mmHg).

  Week 3 - 6 (once)

• Change in intravesical pressure at first sensation measured by UDI from baseline to after completion of 8 weeks of TCSCS

  Utilizing TCSCS and UDI, researchers will test the safety and efficacy of long-term TCSCS in changing intravesical pressure at first sensation (mmHg).

  Week 15-18 (once)

• Change in intravesical pressure at leakage point measured by UDI from baseline to after completion of 8 weeks of TCSCS

  Utilizing TCSCS and UDI, researchers will test the safety and efficacy of long-term TCSCS in changing intravesical pressure at leakage point (mmHg).

  Week 15-18 (once)

• Change in intravesical pressure at maximal volume measured by UDI from baseline to after completion of 8 weeks of TCSCS

  Utilizing TCSCS and UDI, researchers will test the safety and efficacy of long-term TCSCS in changing intravesical pressure at maximal volume (mmHg).

  Week 15-18 (once)

• Change in intravesical pressure at first sensation measured by UDI from baseline to 8 weeks after cessation of TCSCS

  Utilizing TCSCS and UDI, researchers will test the safety and efficacy of TCSCS in changing intravesical pressure at first sensation (mmHg).

  Week 27-30 (once)

• Change in intravesical pressure at leakage point measured by UDI from baseline to 8 weeks after cessation of TCSCS

  Utilizing TCSCS and UDI, researchers will test the safety and efficacy of TCSCS in changing intravesical pressure at leakage point (mmHg).

  Week 27-30 (once)

• Change in intravesical pressure at maximal volume measured by UDI from baseline to 8 weeks after cessation of TCSCS

  Utilizing TCSCS and UDI, researchers will test the safety and efficacy of TCSCS in changing intravesical pressure at maximal volume (mmHg).

  Week 27-30 (once)

• Immediate change in BP during penile or clitoral vibrostimulation

  Genital vibration will be applied by an experienced physician using one or more handheld vibrators placed about the glans penis or the clitoral area with an amplitude of 1.0-3.5 mm and a frequency of 70-100 Hz. Utilizing TCSCS to inhibit nociceptive afferent and continuous beat-by beat BP monitoring via finger photoplethysmography, researchers will test the safety and efficacy of short-term TCS in reproducibly improving AD triggered by vibrostimulation.

  Week 3 - 6 (once)

• Change in BP during penile or clitoral vibrostimulation from baseline to after completion of 8 weeks of TCSCS

  Utilizing TCSCS and continuous beat-by beat BP monitoring via finger photoplethysmography, researchers will test the safety and efficacy of long-term TCSCS in improving AD triggered by vibrostimulation.

  Week 15-18 (once)

• Change in BP during penile or clitoral vibrostimulation from baseline to 8 weeks after cessation of TCSCS

  Utilizing TCSCS to inhibit nociceptive afferent and continuous beat-by beat BP monitoring via finger photoplethysmography, researchers will test the safety and efficacy of TCSCS in improving AD triggered by vibrostimulation.

  Week 27-30 (once)

• Baseline assessment of colonic motility using the wireless motility capsule

  The wireless motility capsule will be ingested and pass naturally through the GI tract, and data will be sent wirelessly to the data receiver. Researchers will use the collected data to assess baseline transit times.

  Week 3 - 6 (once)

• Change in colonic motility using the wireless motility capsule from baseline to after completion of 8 weeks of TCSCS

  Utilizing TCSCS and the wireless motility capsule, researchers will test the safety and efficacy of long-term TCSCS in improving transit times.

  Week 15-18 (once)

• Change in colonic motility using the wireless motility capsule from baseline to 8 weeks after TCSCS cessation.

  Utilizing TCSCS and the wireless motility capsule, researchers will test the safety and efficacy of TCSCS in improving transit times after cessation of therapy.

  Week 27-30 (once)

Secondary Outcomes (9)

• Immediate change in cerebral blood flow (CBF) measured by trans-cranial doppler (TCD) during HUTT

  Week 3 - 6 (once)

• Change in CBF measured by TCD during HUTT from baseline to after completion of 8 weeks of TCSCS

  Week 15-18 (once)

• Change in CBF measured by TCD during HUTT from baseline to 8 weeks after TCSCS cessation

  Week 27-30 (once)

• Immediate change in performance on the verbal fluency test (VFT) during HUTT

  Week 3 - 6 (once)

• Change in performance on the VFT from baseline to after completion of 8 weeks of TCSCS

  Week 15-18 (once)

Other Outcomes (11)

• Frequency of urinary incontinence will be measured using The Incontinence-Quality of Life (I-QoL) questionnaire.

  Week 3 - 6 (once), Week 15-18 (once), week 27-30 (once)

• Neurogenic bladder symptoms will be measured using the Neurogenic Bladder Symptom Score (NBSS).

  Week 3 - 6 (once), Week 15-18 (once), week 27-30 (once)

• Frequency of fecal incontinence will be measured using the modified Wexner Fecal Incontinence Score (WIS).

  Week 3 - 6 (once), Week 15-18 (once), week 27-30 (once)

Study Arms (2)

Group 1 - Thoracic stimulation

EXPERIMENTAL

Participants will receive 8 weeks TCSCS at the mid/low thoracic spinal cord levels.

Device: TESCoN or SCONE device - Thoracic stimulation

Group 2- Lumbosacral stimulation

EXPERIMENTAL

Participants will receive 8 weeks TCSCS at the lumbosacral spinal cord levels.

Device: TESCoN or SCONE device - Lumbosacral stimulation

Interventions

TESCoN or SCONE device - Thoracic stimulation DEVICE

TCSCS will be delivered using a non-invasive central nervous system stimulator (TESCoN or SCONE, SpineX Inc., CA, USA). The stimulation site will be over the thoracic spinal cord.

Group 1 - Thoracic stimulation

TESCoN or SCONE device - Lumbosacral stimulation DEVICE

TCSCS will be delivered using a non-invasive central nervous system stimulator (TESCoN or SCONE, SpineX Inc., CA, USA). The stimulation site will be over the lumbosacral spinal cord.

Group 2- Lumbosacral stimulation

Eligibility Criteria

• Age: 19 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, 19-60 years of age.
• Chronic traumatic SCI (non-progressive, with complete motor paralysis) at or above the T6 spinal segment.
• \>1-year post injury, at least 6 months from any spinal surgery.
• American Spinal Injury Association Impairment Scale (AIS) A, B.
• Stable management of spinal cord related clinical issues (i.e., spasticity management).
• Experience bladder, or bowel, or sexual dysfunction.
• No painful musculoskeletal dysfunction, unhealed fracture, pressure sore, or active infection that may interfere with testing.
• For women of childbearing potential, not intending to become pregnant, currently pregnant, or lactating. The following conditions apply:
• 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.
• Use adequate contraception, or complete abstinence from sexual activities, during the period of the trial and for at least 28 days after completion of treatment.
• If using combined hormonal contraception, a stable regimen during the period of the trial and for at least 28 days after completion of treatment.
• For sexually active males with female partners of childbearing potential, use adequate contraception, or complete abstinence from sexual activities, during the period of the trial and for at least 28 days after completion of treatment.
• Must provide informed consent.
• Willing and able to comply with all clinic visits and study-related procedures.

You may not qualify if:

• Ventilator dependent.
• Signs of lower motor neuron damage (i.e. concomitant conus medullaris/cauda equina injury).
• Severe anemia or hypovolemia as measured by hematocrit via blood test in the last six months.
• History of cardiovascular, respiratory, bladder, or renal disease unrelated to SCI or presence of hydronephrosis or presence of obstructive renal stones.
• History of seizures/epilepsy or recurring headaches.
• Clinically significant, unmanaged, depression (to be screened) or ongoing drug abuse.
• Intrathecal baclofen pump.
• Oral baclofen dose greater than 60mg.
• Individuals that have received intradetrusor or intrasphincter onabotulinumtoxinA injections within 6 months of baseline.
• Any implanted metal (other than dental implants) in the skull or presence of pacemakers, stimulators, or medication pumps in the trunk.
• Past electrode implantation surgery.
• Member of the investigational team or his/her immediate family.
• Presence of severe acute medical issue and use of any specific medication or treatment that, in the investigator's judgement, would adversely affect the participant's participation in the study.
• Known allergies or sensitivities to both blue dye and beetroot powder.
• Known or suspected gastrointestinal obstruction.

Sponsors & Collaborators

• Congressionally Directed Medical Research Programs: collaborator
• University of British Columbia: lead
• United States Department of Defense: collaborator

Study Sites (2)

Blusson Spinal Cord Centre

Vancouver, British Columbia, V5Z 1M9, Canada

RECRUITING

St Paul's Hospital

Vancouver, British Columbia, V6Z 1Y6, Canada

RECRUITING

MeSH Terms

Conditions

Spinal Cord Injuries; Primary Dysautonomias; Sexual Dysfunction, Physiological; Autonomic Dysreflexia; Hypotension, Orthostatic

Condition Hierarchy (Ancestors)

Spinal Cord Diseases; Central Nervous System Diseases; Nervous System Diseases; Trauma, Nervous System; Wounds and Injuries; Autonomic Nervous System Diseases; Genital Diseases; Urogenital Diseases; Orthostatic Intolerance; Hypotension; Vascular Diseases; Cardiovascular Diseases

Study Officials

• Andrei Krassioukov, MD, PhD, FRCPC

  The University of British Columbia, International Collaboration on Repair Discoveries (ICORD)

  PRINCIPAL INVESTIGATOR

Central Study Contacts

Andrea L. Maharaj, BSc

CONTACT

604-675-8856; AMaharaj@icord.org

Soshi Samejima, PhD

CONTACT

604 675 8816; soshi@icord.org

Study Design

• Study Type: interventional
• Phase: not applicable
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Professor

Model Details: Using a randomized counter-balanced approach, individuals will be allocated in two distinct pathways; the participants in Groups 1 (thoracic stimulation) and Group 2 (lumbosacral stimulation) will receive 8 weeks of TCSCS (3 times/week) at either mid/low thoracic or lumbosacral spinal cord levels respectively.

Study Record Dates

• First Submitted: March 21, 2022
• First Posted: May 11, 2022
• Study Start: October 3, 2023
• Primary Completion (Estimated): October 1, 2026
• Study Completion (Estimated): October 1, 2027
• Last Updated: December 8, 2025

Record last verified: 2025-11

Data Sharing

• IPD Sharing: Will share
• Shared Documents: STUDY PROTOCOL, SAP, ANALYTIC CODE
• Time Frame: Data will be available upon full-text print publication in a peer-reviewed journal, for a duration of at least 10 years.
• Access Criteria: Online access or e-mail request to the corresponding author from an established scientific investigator

Locations

CA (2)