Clinical trial NCT05369520: Noninvasive Spinal Cord Stimulation for Recovery of Autonomic Function After Spinal Cord Injury
Official title: Noninvasive Spinal Cord Stimulation for Recovery of Autonomic Function After Spinal Cord Injury: Moving From Mechanisms to Clinical Practice
Study type: INTERVENTIONAL
Overall status: NOT_YET_RECRUITING
Phase: NA
Conditions: Spinal Cord Injuries
Autonomic Dysfunction
Lead sponsor: University of British Columbia
Sponsor class: OTHER
Collaborators: name: United States Department of Defense
First posted: 2022-05-11
Enrollment: 30
Sex: ALL
Minimum age (years): 18
Maximum age (years): 60
Standard ages: ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Intervention model description: 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.
Primary purpose: TREATMENT

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).

Detailed 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.

Eligibility criteria: 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.

Primary outcomes:
measure: Targeted TCSCS map modulate resting blood pressure (BP)
timeFrame: Week 1-2 (once)
measure: Targeted TCSCS map to activate to activate skeletal muscles and pelvic floor muscles
timeFrame: Week 1-2 (once)
measure: Immediate change in BP during the head up tilt test (HUTT)
timeFrame: Week 3 - 6 (once)
measure: Change in BP during the head up tilt test (HUTT) from baseline to after completion of 8 weeks of TCSCS
timeFrame: Week 15-18 (once)
measure: Change in BP during the head up tilt test (HUTT) from baseline to 8 weeks after cessation of TCSCS
timeFrame: Week 27-30 (once)
measure: Immediate change in BP during digital anorectal stimulation (DARS)
timeFrame: Week 3 - 6 (once)
measure: Change in BP during digital anorectal stimulation (DARS) from baseline to after completion of 8 weeks of TCSCS
timeFrame: Week 15-18 (once)
measure: Change in BP during digital anorectal stimulation (DARS) from baseline to 8 weeks after cessation of TCSCS
timeFrame: Week 27-30 (once)
measure: Immediate change in rectal pressure measured by anorectal manometry (ARM)
timeFrame: Week 3 - 6 (once)
measure: Immediate change in high pressure anal canal zone measured by ARM
timeFrame: Week 3 - 6 (once)
measure: Immediate change in recto-anal inhibitory reflex measured by ARM
timeFrame: Week 3 - 6 (once)
measure: Immediate change in rectal sensation measured by ARM
timeFrame: Week 3 - 6 (once)
measure: Change in rectal pressure measured by ARM from baseline to after completion of 8 weeks of TCSCS
timeFrame: Week 15-18 (once)
measure: Change in high pressure anal canal zone measured by ARM from baseline to after completion of 8 weeks of TCSCS
timeFrame: Week 15-18 (once)
measure: Change in rectal sensation measured by ARM from baseline to after completion of 8 weeks of TCSCS
timeFrame: Week 15-18 (once)
measure: Change in recto-anal inhibitory reflex measured by ARM from baseline to after completion of 8 weeks of TCSCS
timeFrame: Week 15-18 (once)
measure: Change in rectal pressure measured by anorectal manometry (ARM) from baseline to 8 weeks after cessation of TCSCS
timeFrame: Week 27-30 (once)
measure: Change in high pressure anal canal zone measured by anorectal manometry (ARM) from baseline to 8 weeks after cessation of TCSCS
timeFrame: Week 27-30 (once)
measure: Change in recto-anal inhibitory reflex measured by anorectal manometry (ARM) from baseline to 8 weeks after cessation of TCSCS
timeFrame: Week 27-30 (once)
measure: Change in rectal sensation measured by anorectal manometry (ARM) from baseline to 8 weeks after cessation of TCSCS
timeFrame: Week 27-30 (once)
measure: Immediate change in intravesical pressure at first sensation measured by urodynamic investigation (UDI)
timeFrame: Week 3 - 6 (once)
measure: Immediate change in intravesical pressure at leakage point measured by UDI
timeFrame: Week 3 - 6 (once)
measure: Immediate change in intravesical pressure at maximal volume measured by UDI
timeFrame: Week 3 - 6 (once)
measure: Change in intravesical pressure at first sensation measured by UDI from baseline to after completion of 8 weeks of TCSCS
timeFrame: Week 15-18 (once)
measure: Change in intravesical pressure at leakage point measured by UDI from baseline to after completion of 8 weeks of TCSCS
timeFrame: Week 15-18 (once)
measure: Change in intravesical pressure at maximal volume measured by UDI from baseline to after completion of 8 weeks of TCSCS
timeFrame: Week 15-18 (once)
measure: Change in intravesical pressure at first sensation measured by UDI from baseline to 8 weeks after cessation of TCSCS
timeFrame: Week 27-30 (once)
measure: Change in intravesical pressure at leakage point measured by UDI from baseline to 8 weeks after cessation of TCSCS
timeFrame: Week 27-30 (once)
measure: Change in intravesical pressure at maximal volume measured by UDI from baseline to 8 weeks after cessation of TCSCS
timeFrame: Week 27-30 (once)
measure: Immediate change in BP during penile or clitoral vibrostimulation
timeFrame: Week 3 - 6 (once)
measure: Change in BP during penile or clitoral vibrostimulation from baseline to after completion of 8 weeks of TCSCS
timeFrame: Week 15-18 (once)
measure: Change in BP during penile or clitoral vibrostimulation from baseline to 8 weeks after cessation of TCSCS
timeFrame: Week 27-30 (once)
measure: Baseline assessment of colonic motility using the wireless motility capsule
timeFrame: Week 3 - 6 (once)
measure: Change in colonic motility using the wireless motility capsule from baseline to after completion of 8 weeks of TCSCS
timeFrame: Week 15-18 (once)
measure: Change in colonic motility using the wireless motility capsule from baseline to 8 weeks after TCSCS cessation.
timeFrame: Week 27-30 (once)
Secondary outcomes:
measure: Immediate change in cerebral blood flow (CBF) measured by trans-cranial doppler (TCD) during HUTT
timeFrame: Week 3 - 6 (once)
measure: Change in CBF measured by TCD during HUTT from baseline to after completion of 8 weeks of TCSCS
timeFrame: Week 15-18 (once)
measure: Change in CBF measured by TCD during HUTT from baseline to 8 weeks after TCSCS cessation
timeFrame: Week 27-30 (once)
measure: Immediate change in performance on the verbal fluency test (VFT) during HUTT
timeFrame: Week 3 - 6 (once)
measure: Change in performance on the VFT from baseline to after completion of 8 weeks of TCSCS
timeFrame: Week 15-18 (once)
measure: Change in performance on the VFT from baseline to 8 weeks after TCSCS cessation
timeFrame: Week 27-30 (once)
measure: Immediate change in performance on the Stroop Color and Word (SCW) test during HUTT
timeFrame: Week 3 - 6 (once)
measure: Change in performance on SCW from baseline to after completion of 8 weeks of TCSCS
timeFrame: Week 15-18 (once)
measure: Change in performance on SCW from baseline to 8 weeks after TCSCS cessation
timeFrame: Week 27-30 (once)
Other outcomes:
measure: Frequency of urinary incontinence will be measured using The Incontinence-Quality of Life (I-QoL) questionnaire.
timeFrame: Week 3 - 6 (once), Week 15-18 (once), week 27-30 (once)
measure: Neurogenic bladder symptoms will be measured using the Neurogenic Bladder Symptom Score (NBSS).
timeFrame: Week 3 - 6 (once), Week 15-18 (once), week 27-30 (once)
measure: Frequency of fecal incontinence will be measured using the modified Wexner Fecal Incontinence Score (WIS).
timeFrame: Week 3 - 6 (once), Week 15-18 (once), week 27-30 (once)
measure: Neurogenic bowel symptoms will be measured using the Neurogenic Bowel Dysfunction (NBD) score.
timeFrame: Week 3 - 6 (once), Week 15-18 (once), week 27-30 (once)
measure: Time Needed for Bowel Movement (TNFBM) will be measured by self-report.
timeFrame: Week 3 - 6 (once), Week 15-18 (once), week 27-30 (once)
measure: Participant's sexual function and satisfaction with their overall sexual life will be measured using the International Index of Erectile Function (IIEF-15).
timeFrame: Week 3 - 6 (once), Week 15-18 (once), week 27-30 (once)
measure: Participant's sexual function and satisfaction with their overall sexual life will be measured using the Female Sexual Function Index (FSFI).
timeFrame: Week 3 - 6 (once), Week 15-18 (once), week 27-30 (once)
measure: Participant's sexual function and satisfaction with their overall sexual life will be measured using a semi-structured qualitative interview.
timeFrame: Week 3 - 6 (once), Week 15-18 (once), week 27-30 (once)
measure: Participant's sexually related personal distress will be measured using the Female Sexual Distress Scale (FSDS).
timeFrame: Week 3 - 6 (once), Week 15-18 (once), week 27-30 (once)
measure: Participant's sensations associated with orgasm will be measured using the Orgasm Rating Scale (ORS).
timeFrame: Week 3 - 6 (once), Week 15-18 (once), week 27-30 (once)
measure: Participant's quality of life will be measured using the Short Form Health Survey (SF-36)
timeFrame: Week 3 - 6 (once), Week 15-18 (once), week 27-30 (once)
Locations:
city: Vancouver
country: Canada
facility: Blusson Spinal Cord Centre
state: British Columbia
city: Vancouver
country: Canada
facility: St Paul's Hospital
state: British Columbia
Study officials:
affiliation: The University of British Columbia, International Collaboration on Repair Discoveries (ICORD)
name: Andrei Krassioukov, MD, PhD
role: PRINCIPAL_INVESTIGATOR
References: