Noninvasive Spinal Cord Stimulation for Recovery of Autonomic Function After Spinal Cord Injury

Spinal Cord Injuries Clinical Trial

Official title:

Noninvasive Spinal Cord Stimulation for Recovery of Autonomic Function After Spinal Cord Injury: Moving From Mechanisms to Clinical Practice

Clinical Trial Details — Status: Not yet recruiting

Administrative data

• NCT number: NCT05369520
• Other study ID #: H22-00365
• Status: Not yet recruiting
• Phase: N/A
• Start date: January 2023
• Est. completion date: September 2027

Study information

• Verified date: October 2022
• Source: University of British Columbia
• Contact: Jennifer Phan, BSc
• Phone: 604 675 8856
• Email: jennifer.phan[@]vch.ca
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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).

Description:

This is a pilot clinical trial to explore the efficacy of TCSCS (proof-of-concept) in mitigating crucial autonomic dysfunctions that impact the health-related quality of life of individuals with SCI. A total of 30 eligible participants will be recruited and attend forty-two visits. All experiments will be performed at ICORD (Primary site) and the Brenda and David McLean Integrated Spine Clinic (SCI clinic), with the exception of anorectal manometry testing conducted at the Gastroenterology Clinic, St Paul's Hospital (GI clinic). Following completion of screening and signing informed consent forms, participants will undergo spatiotemporal mapping of spinal cord segments known to be involved in blood pressure, lower urinary tract and bowel control (visit 2). Following mapping, all individuals will undergo baseline functional assessments during 5 visits (visits 3-7), over a period of 4 weeks. To minimize the order effect, the functional assessments will be performed in a randomized order. Following baseline assessments, using a randomized counter-balanced approach, individuals will be allocated in two distinct pathways; the participants in Groups 1 and 2 will receive 8 weeks of TCSCS (3 times/week) at either mid/low thoracic or lumbosacral spinal cord levels respectively (visits 8- 31). Following long-term TCSCS, participants will undergo functional assessments during 5 visits (visits 32- 36) over a period of 4 weeks. In order to evaluate the persistent effects of TCSCS, all assessments will be repeated 8 weeks after cessation of the therapy.

Recruitment information / eligibility

• Status: Not yet recruiting
• Enrollment: 30
• Est. completion date: September 2027
• Est. primary completion date: September 2025
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years to 60 Years

Eligibility

Inclusion Criteria:

• 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.
• >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).
• Documented impaired lower urinary tract, bowel or sexual function.
• 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:

1. 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. Use adequate contraception, or practice complete abstinence from sexual activities, during the period of the trial and for at least 28 days after completion of treatment.

3. If using combined hormonal contraceptives, 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 practice 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.
• 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).

Exclusion Criteria:

• Ventilator dependent.
• Signs of lower motor neuron damage (i.e. concomitant conus medullaris/cauda equina injury).
• Severe anemia (Hgb<8 g/dl) 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.
• History of gastrointestinal atresia or stenosis.
• Clinically significant, unmanaged, depression (PHQ-9 above 15) or ongoing drug abuse.
• Intrathecal baclofen pump.
• Oral baclofen dose > 60mg.
• Individuals that have received intradetrusor or intrasphincter onabotulinumtoxinA injections within 9 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.

Related Conditions & MeSH terms

• Autonomic Dysfunction
• Autonomic Nervous System Diseases
• Primary Dysautonomias
• Spinal Cord Injuries
• Wounds and Injuries

Intervention

Device:
• TESCoN device - Thoracic stimulation
TCSCS will be delivered using a non-invasive central nervous system stimulator (TESCoN, SpineX Inc., CA, USA). The stimulation site will be over the thoracic spinal cord (T7-T12, Group 1).
• TESCoN device - Lumbosacral stimulation
TCSCS will be delivered using a non-invasive central nervous system stimulator (TESCoN, SpineX Inc., CA, USA). The stimulation site will be over the lumbosacral spinal cord (L1 - L3, Group 2).

Locations

Country	Name	City	State
Canada	Blusson Spinal Cord Centre	Vancouver	British Columbia
Canada	St Paul's Hospital	Vancouver	British Columbia

Sponsors (2)

Lead Sponsor	Collaborator
University of British Columbia	United States Department of Defense

Country where clinical trial is conducted

Canada, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Other	Frequency of urinary incontinence will be measured using The Incontinence-Quality of Life (I-QoL) questionnaire.	Assessment of urinary incontinence will be performed to assess the impact of long term TCSCS on this measure. The scale is a 100 point scale where 0 is most severe incontinence.	Week 3 - 6 (once), Week 15-18 (once), week 27-30 (once)
Other	Neurogenic bladder symptoms will be measured using the Neurogenic Bladder Symptom Score (NBSS).	Assessment of neurogenic bladder symptoms will be performed to assess the impact of long term TCSCS on this measure. The score measures bladder symptoms across 3 different domains: incontinence (scored 0-29), storage and voiding (scored 0-22), and consequences (scored 0-23), with higher scores representing worse symptoms.	Week 3 - 6 (once), Week 15-18 (once), week 27-30 (once)
Other	Frequency of fecal incontinence will be measured using the modified Wexner Fecal Incontinence Score (WIS).	Assessment of fecal incontinence will be performed to assess the impact of long term TCSCS on this measure. Scores can range from 0-20, with a higher score representing greater incontinence.	Week 3 - 6 (once), Week 15-18 (once), week 27-30 (once)
Other	Neurogenic bowel symptoms will be measured using the Neurogenic Bowel Dysfunction (NBD) score.	Assessment of neurogenic bowel symptoms will be performed to assess the impact of long term TCSCS on this measure. Scores can range from 0-47, with a higher score representing more severe dysfunction.	Week 3 - 6 (once), Week 15-18 (once), week 27-30 (once)
Other	Time Needed for Bowel Movement (TNFBM) will be measured by self-report.	Participants will be asked to record the time from 'suppository insertion' to 'when bowel evacuation is completed', during their regular bowel movement at home.	Week 3 - 6 (once), Week 15-18 (once), week 27-30 (once)
Other	Participant's sexual function and satisfaction with their overall sexual life will be measured using the International Index of Erectile Function (IIEF-15).	This measure of sexual function will be used to assess whether sexual function is impacted by TCSCS. Scores can range from 5-25, with higher scores representing greater function.	Week 3 - 6 (once), Week 15-18 (once), week 27-30 (once)
Other	Participant's sexual function and satisfaction with their overall sexual life will be measured using the Female Sexual Function Index (FSFI).	This measure of sexual function will be used to assess whether sexual function is impacted by TCSCS. Scores can range from 2-36, with higher scores representing greater function.	Week 3 - 6 (once), Week 15-18 (once), week 27-30 (once)
Other	Participant's sexual function and satisfaction with their overall sexual life will be measured using a semi-structured qualitative interview.	This measure of sexual function will be used to assess whether sexual function is impacted by TCSCS.	Week 3 - 6 (once), Week 15-18 (once), week 27-30 (once)
Other	Participant's sexually related personal distress will be measured using the Female Sexual Distress Scale (FSDS).	The FSDS is a 13-item self-report measure of sexually related personal distress in women. The 13 items of the scale are scored on a 5-point Likert scale ranging from 0 (never) to 4 (always). The total score is calculated as the sum of the responses and ranges from 0 to 52, with higher scores indicating a greater level of distress. A score of =11 serves as a cut-off value for diagnosing women with sexual distress.	Week 3 - 6 (once), Week 15-18 (once), week 27-30 (once)
Other	Participant's sensations associated with orgasm will be measured using the Orgasm Rating Scale (ORS).	The ORS is a 28 item self-report measure of phenomenological sensations associated with orgasm in men and women. Items are scored from 0 (not at all) 5 (extremely), with total scores ranging from 0 to 140, and higher scores indicating better function.	Week 3 - 6 (once), Week 15-18 (once), week 27-30 (once)
Other	Participant's quality of life will be measured using the Short Form Health Survey (SF-36)	The SF-36 consists of 8 domains pertaining to the respondents' 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.	Week 3 - 6 (once), Week 15-18 (once), week 27-30 (once)
Primary	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)
Primary	Targeted TCSCS map to activate 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)
Primary	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)
Primary	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)
Primary	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)
Primary	Immediate change in BP during digital anorectal stimulation (DARS)	DARS is a routine procedure to initiate a bowel routine, with the participant laying 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)
Primary	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)
Primary	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)
Primary	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)
Primary	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)
Primary	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)
Primary	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)
Primary	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)
Primary	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)
Primary	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)
Primary	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)
Primary	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)
Primary	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)
Primary	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)
Primary	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)
Primary	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)
Primary	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)
Primary	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)
Primary	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)
Primary	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)
Primary	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)
Primary	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)
Primary	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)
Primary	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)
Primary	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)
Primary	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)
Primary	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)
Primary	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)
Primary	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)
Primary	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	Immediate change in cerebral blood flow (CBF) measured by trans-cranial doppler (TCD) during HUTT	TCD is a non-invasive ultrasound technique used to measure real-time CBF velocity. Researchers will test the safety and efficacy of short-term TCSCS in reproducibly improving CBF during HUTT.	Week 3 - 6 (once)
Secondary	Change in CBF measured by TCD during HUTT from baseline to after completion of 8 weeks of TCSCS	Researchers will test the safety and efficacy of long-term TCSCS in improving CBF during HUTT.	Week 15-18 (once)
Secondary	Change in CBF measured by TCD during HUTT from baseline to 8 weeks after TCSCS cessation	Researchers will test the safety and efficacy of TCSCS in improving CBF during HUTT after cessation of therapy.	Week 27-30 (once)
Secondary	Immediate change in performance on the verbal fluency test (VFT) during HUTT	Phonetic/letter fluency, specifically total number of words, will be measured using the verbal fluency test (VFT). Researchers will test the safety and efficacy of short-term TCSCS in reproducibly improving cognitive function during HUTT.	Week 3 - 6 (once)
Secondary	Change in performance on the VFT from baseline to after completion of 8 weeks of TCSCS	Researchers will test the safety and efficacy of long-term TCSCS in improving phonetic/letter fluency using the VFT.	Week 15-18 (once)
Secondary	Change in performance on the VFT from baseline to 8 weeks after TCSCS cessation	Researchers will test the safety and efficacy of TCSCS in improving phonetic/letter fluency after cessation of therapy.	Week 27-30 (once)
Secondary	Immediate change in performance on the Stroop Color and Word (SCW) test during HUTT	Ability to inhibit cognitive interference, specifically completion time, will be measured using the Stroop Color and Word (SCW) test. Researchers will test the safety and efficacy of short-term TCSCS in reproducibly improving completion time of the SCW.	Week 3 - 6 (once)
Secondary	Change in performance on SCW from baseline to after completion of 8 weeks of TCSCS	Researchers will test the safety and efficacy of short-term TCSCS in reproducibly improving completion time of the SCW.	Week 15-18 (once)
Secondary	Change in performance on SCW from baseline to 8 weeks after TCSCS cessation	Researchers will test the safety and efficacy of short-term TCSCS in reproducibly improving completion time of the SCW after cessation of therapy.	Week 27-30 (once)