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

Официальное название

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

Обзор

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).

Подробное описание

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 (visit 1), 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 with and without TCSCS 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.

Вмешательства

• Устройство TESCoN or SCONE device - Thoracic stimulation
  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.
• Устройство TESCoN or SCONE device - Lumbosacral stimulation
  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.

Первичные конечные точки

• Targeted TCSCS map modulate resting blood pressure (BP) [Срок оценки: Week 1-2 (once)]
• Targeted TCSCS map to activate skeletal muscles and pelvic floor muscles [Срок оценки: Week 1-2 (once)]
• Immediate change in BP during the head up tilt test (HUTT) [Срок оценки: Week 3 - 6 (once)]
• Change in BP during the head up tilt test (HUTT) from baseline to after completion of 8 weeks of TCSCS [Срок оценки: Week 15-18 (once)]
• Change in BP during the head up tilt test (HUTT) from baseline to 8 weeks after cessation of TCSCS [Срок оценки: Week 27-30 (once)]
• Immediate change in BP during digital anorectal stimulation (DARS) [Срок оценки: Week 3 - 6 (once)]
• Change in BP during digital anorectal stimulation (DARS) from baseline to after completion of 8 weeks of TCSCS [Срок оценки: Week 15-18 (once)]
• Change in BP during digital anorectal stimulation (DARS) from baseline to 8 weeks after cessation of TCSCS [Срок оценки: Week 27-30 (once)]
• Immediate change in rectal pressure measured by anorectal manometry (ARM) [Срок оценки: Week 3 - 6 (once)]
• Immediate change in high pressure anal canal zone measured by ARM [Срок оценки: Week 3 - 6 (once)]

Вторичные конечные точки (9)

• Immediate change in cerebral blood flow (CBF) measured by trans-cranial doppler (TCD) during HUTT [Срок оценки: Week 3 - 6 (once)]
• Change in CBF measured by TCD during HUTT from baseline to after completion of 8 weeks of TCSCS [Срок оценки: Week 15-18 (once)]
• Change in CBF measured by TCD during HUTT from baseline to 8 weeks after TCSCS cessation [Срок оценки: Week 27-30 (once)]
• Immediate change in performance on the verbal fluency test (VFT) during HUTT [Срок оценки: Week 3 - 6 (once)]
• Change in performance on the VFT from baseline to after completion of 8 weeks of TCSCS [Срок оценки: Week 15-18 (once)]
• Change in performance on the VFT from baseline to 8 weeks after TCSCS cessation [Срок оценки: Week 27-30 (once)]
• Immediate change in performance on the Stroop Color and Word (SCW) test during HUTT [Срок оценки: Week 3 - 6 (once)]
• Change in performance on SCW from baseline to after completion of 8 weeks of TCSCS [Срок оценки: Week 15-18 (once)]
• Change in performance on SCW from baseline to 8 weeks after TCSCS cessation [Срок оценки: Week 27-30 (once)]

Критерии участия

Критерии включения

• 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.
• 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).

Критерии исключения

• 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.
• Persons with active inflammatory bowel disease or a history of bowel perforation.

Критерии приведены из реестра в оригинале (на английском). Окончательную оценку соответствия проводит исследовательский центр.

Здоровые добровольцы: Нет

Дизайн исследования

Распределение

Рандомизированное

Модель

Параллельные группы

Маскирование

Открытое

Основная цель

Лечение

Центры проведения

Канада · 2 центра

• Blusson Spinal Cord Centre — Vancouver
• St Paul's Hospital — Vancouver

Публикации

• Malik RN, Sobeeh MG, Maharaj AL, Shackleton C, Hosseinzadeh A, Saloojee M, Khavandegar A, Kontaxakis A, Thordarson T, Chang C, Balthazaar SJT, Williams AMM, Lam T, Ghuman A, Anderson K, Elliott SL, Berger MJ, Samejima S, Sachdeva R, Krassioukov AV. Moving from mechanisms to clinical practice: non-invasive spinal cord stimulation for recovery of autonomic functions after spinal cord injury - a prot PMID 42203266
• Malik RN, Samejima S, Williams AMM, Hosseinzadeh A, Ogalo E, Stolz A, Lam C, Shackleton C, Miller T, Sobeeh MG, Boyd LA, Kramer JLK, Lam T, Sachdeva R, Berger MJ, Krassioukov AV. Non-invasive spinal cord neuromodulation enables volitional anti-gravity leg movements after motor-complete spinal cord injury: responders vs. non-responders. J Neuroeng Rehabil. 2026 May 18;23(1):216. doi: 10.1186/s12984 PMID 42152086

Идентификаторы

NCT: NCT05369520 · H22-00365 · CDMRP-SC210078

Первоисточники (государственные реестры)

• ClinicalTrials.gov (NIH, США)

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