Clinical trial NCT06520020: Evaluating Safety and Feasibility of Transcutaneous Spinal Cord Stimulation Following Traumatic and Non-Traumatic Spinal Cord Injury: A Pilot Study
Official title: Evaluating Safety and Feasibility of Transcutaneous Spinal Cord Stimulation Following Traumatic and Non-Traumatic Spinal Cord Injury: A Pilot Study
Study type: INTERVENTIONAL
Overall status: RECRUITING
Phase: NA
Conditions: Spinal Cord Stimulation
Electric Stimulation Therapy
Traumatic Spinal Cord Injury
Cervical Myelopathy
Keywords: Stimulation
Transcutaneous
MagStim
Transcranial
Magnetic
Lead sponsor: University of Kentucky
Sponsor class: OTHER
First posted: 2024-07-25
Enrollment: 30
Sex: ALL
Minimum age (years): 18
Maximum age (years): 80
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NON_RANDOMIZED
Intervention model: PARALLEL
Intervention model description: The study will be a non-randomized, non-blinded pilot study to analyze the safety and feasibility of a non-significant risk device, using transcutaneous spinal cord stimulation.

We aim to include 30 total patients, 10 patients in each of 3 groups:

1. Non-traumatic spinal cord injury (ntSCI) with diagnosis of degenerative cervical myelopathy and offered surgical intervention.
2. Early tSCI screened during the hospital admission when cervical/thoracic spinal injury was diagnosed.
3. Delayed tSCI (control) screened 6-24 months after acute cervical/thoracic spinal injury.
Primary purpose: TREATMENT

Brief summary: The study will be a non-randomized, non-blinded pilot study to analyze the safety and feasibility of a non-significant risk device, transcutaneous spinal cord stimulation. The aim is to include 30 total patients, 10 patients in each of 3 groups:

1. Non-traumatic spinal cord injury (ntSCI) with diagnosis of degenerative cervical myelopathy and offered surgical intervention.
2. Early tSCI screened during the hospital admission when cervical/thoracic spinal injury was diagnosed.
3. Delayed tSCI (control) screened 6-24 months after acute cervical/thoracic spinal injury.

Detailed description: Spinal cord injury (SCI) can result from primary physical insults such as acute trauma, or secondary insults that result from chronic compression and ischemia. The resultant neurological impairment leads to high personal and societal burden. There are few effective therapies to improve function for those living with SCI. Spinal cord stimulation (SCS) represents a safe and potentially effective treatment for persons with SCI-related pain and paralysis. The aim of this study is to investigate the potential clinical utility of SCS delivered transcutaneously in patients at various stages of SCI, resulting from traumatic and non-traumatic mechanisms. This study will evaluate the ability to safely stimulate the injured spinal cord at defined intervals and record autonomic and sensorimotor function of participants across their admission, rehabilitation, and clinical follow-up.

Various upper and lower extremity-related functional measures will be assessed at baseline and at established follow-up timepoints across a 12-month period. The safety of this intervention, and the utility of each outcome measure will be the primary outcome of the study. To our knowledge, there are no reported clinical trials that have evaluated multi-modal outcomes of SCS. Furthermore, there are no proposed trials of SCS for these SCI subtypes across the post-injury spectrum posted to the platform clinicaltrials.gov. Data obtained from this pilot evaluation will be used to inform an early phase Ib/II trial of efficacy for improvement of paralysis, autonomic dysfunction, and pain following SCI.

Over 2.5 million Americans are living with various forms of SCI, equating to substantial individual and societal burden (1). Acute traumatic SCI average costs alone range from $380K to $1.4M. This high socioeconomic impact has undergone significant inflation with estimated annual costs of $4 billion in 1990, recently increasing to $23 billion. Approximately 13,000 new traumatic SCI events are noted yearly in North America. Degenerative cervical myelopathy (DCM) represents the most prevalent etiology of nontraumatic spinal cord (ntSCI) and dysfunction in adults. The prevalence of ntSCI is order(s) of magnitude higher than that of tSCI.

Together, these conditions significantly impact millions of North Americans often with greater personal impact that chronic conditions such as diabetes or cardiac disease. The considerable societal concern due to this individual disability is compounded by the lack of viable treatment options.

DCM arises from age-related degenerative processes, leading to osteophyte development, facet joint enlargement, ossification of spinal ligaments, and disk protrusion. These arthritic changes collectively compress the spinal cord causing injury with associated ischemia and inflammation. In turn, a similar constellation of symptoms develop including extremity pain, reduced motor function, numbness, hemodynamic lability, urinary incontinence, bowel dysfunction, and walking instability contributing towards higher years lived with disability (DALYs) as well as overall economic burden.

Currently, effective evidence-proven treatments are restricted to surgical decompression and rehabilitation. Narrative studies have shown that patients living with paralysis want options for neural modulation therapies, as they perceive the risk-to-benefit ratio of implanted devices more favorably than healthcare professionals. Given overall suboptimal outcomes in patients with SCI, it is critical to further enhance both the recovery rates and the extent of recovery beyond what is achievable through surgical decompression.

Spinal cord stimulation has been shown to mediate functional improvement following acute traumatic SCI in terms of limb function, ambulation, hand strength, autonomic dysfunction, intractable pain, and bladder control. The majority of published studies have applied stimulation during the chronic phase of recovery, and largely in a single or small group of participants.

Variable applications of SCS for SCI have yet to be demonstrated using multi-modality stimulation, such as spinal transcutaneous, spinal epidural, and transcranial magnetic stimulation of the motor cortex. Harkema and colleagues demonstrated that epidural SCS can return volitional motor control in participants who had none following chronic thoracic injury. Their work at the University of Louisville also has shown that multilevel transcutaneous spinal cord stimulation can be applied to several cervicothoracic regions spanning across the entire limb enlargement, and provide sensorimotor functional improvements during neurorehabilitation. These approaches have subsequently been applied at other centers with success for sensorimotor recovery.

The utilization of SCS in managing Failed Back Surgery Syndrome (FBSS), Complex Regional Pain Syndrome (CRPS), and chronic leg ischemia has been well documented. However, there is limited evidence indicating the use of SCS in patients with tSCI or ntSCI with regards to improving motor functions. This application of SCS could identify important differentiators in neural modulation that will correspond to improved functional outcomes, patient reported outcome measures (PROM), and quality of life (QoL). Should differentiators be observed, these conclusions will inform phase Ib/II study of SCS-based neuromodulation vs standard-of-care rehabilitation. This is directly in line with the best-of-practice and goals promoted by the leaders in SCI clinical research and patient-driven goals.

To date, there are no reported clinical trials involving participants in the subacute phase of tSCI, despite the widely-held belief that this phase offers the greatest potential for therapeutic intervention to reduce secondary injury and preserve functional networks.

Likewise, there are no clinical trials examining the role of perioperative SCS in patients diagnosed with any form of ntSCI (including patients with DCM who undergo surgical decompression).

The proposed study will directly address whether neuromodulation has a specific therapeutic potential for persons having sustained acute traumatic and non-traumatic spinal injuries. This study will specifically address whether this can be achieved with a non-significant risk device such as transcutaneous spinal cord stimulation. Lastly, this study will comparatively assess the modalities that can be used to reliably stimulate and measure the physiologic effects of neuromodulation of the injured spinal cord.

Additionally, this study aims to test the hypothesis that transcutaneous electrical spinal cord stimulation has equivalent modulatory effect on sensorimotor pathways and spinal cord function. This study will prospectively record neurologic outcomes to fully leverage the technologies at our disposal and maximize the potential benefit for each participant. The subsequent results will further help determine whether spinal cord neuromodulation can be directly correlated to either patient reported outcome or functional performance measures. Moreover, to determine feasibility of transcutaneous SCS at various timepoints after presentation, this study will measure spinal signal outputs before and after standard-of-care treatments including surgery and intensive neural rehabilitation.

The preliminary data in support of SCS for individuals with tSCI applied at chronic recovery phases has demonstrated promising outcomes, potentially ameliorating this severe condition. The investigation into utilizing SCS as a management approach for acute tSCI and ntSCI (ie. DCM), in conjunction with surgical interventions and rehabilitation, represents a promising prospect for enhancing the quality of life of those afflicted with this debilitating neurological disorder.

Eligibility criteria: Inclusion Criteria:

* Age: = 18 years and = 80 years.
* Written informed consent by patient and/or legal authorized representative (LAR).
* No other life-threatening condition.
* No evidence of sepsis.
* No evidence of superficial skin infection at site of surgery and intervention.
* An established diagnosis of either:

  * cervical myelopathy with modified Japanese Orthopaedic Association score of 8-14, or
  * acute cervical / thoracic SCI with ASIA Impairment Scale grade A-D (as assessed within 72 hours of injury) with neurologic level of injury (NLI) from C2 to T12.
* The ability to undergo, or have had, surgical intervention. -. The ability to undergo transcutaneous intervention including study procedures in the posterior cervical or thoracic midline at or after 14 days from surgery.

Exclusion Criteria:

* Any concomitant impairment of the upper and lower limb at baseline that could potentially confound the neurologic assessments; including but not limited to traumatic or disease conditions like brachial plexus injury, peripheral neuropathy, spinal hematoma, transverse myelitis, non-compressive myelopathy, dementia, and Parkinson's disease.
* mJOA of \>= 15 and \<= 7, or AIS grade E tSCI at baseline assessment.
* Currently involved in another non-observational ntSCI or tSCI study, or receiving another interventional drug, that could interfere with recordings and confound adverse events.
* Other illness (including mental disorder) that could preclude accurate medical and neurological evaluation, at discretion of the treating surgeon and/or principal investigator.
* Unable to commit to the follow-up schedule.
* Recent history of regular substance abuse (illicit drugs, alcohol), which in the opinion of the investigator would interfere with the subject's participation in the study.
* Any condition likely to result in the patient's death within the next 12 months.
* Prisoner.
* Pregnancy.
* Cardiac pacemaker dependent, unable to undergo electrical stimulation.
* Brain implant, skull prosthesis, plate and screws limiting transcranial stimulation.
* Tattoo at site of skin electrode that causes heat/pain during stimulation.
* Subjects who in the opinion of the investigator are not suitable for inclusion in the study, with reason documented.

Primary outcomes:
measure: International Standards for Neurological Classification of Spinal Cord Injury (ISNCSCI)
timeFrame: Twelve Months
measure: ASIA Impairment Scale (ASIA / AIS)
timeFrame: Twelve Months
measure: Modified Japanese Orthopaedic Association (mJOA)
timeFrame: Perioperative
measure: Blood Pressure
timeFrame: Perioperative
measure: Orthostatic Blood Pressure
timeFrame: Perioperative
measure: Post-Void Residual
timeFrame: Perioperative
measure: Upper Extremity: Grip Strength
timeFrame: Twelve Months
measure: GRASSP
timeFrame: Twelve Months
measure: Lower Extremity: 10 Meter Walk Test
timeFrame: Twelve Months
measure: GAITRite Walking Assessment
timeFrame: Twelve Months
measure: SCIM-vIII (PROM)
timeFrame: Twelve Months
measure: WHOQOL-BREF
timeFrame: Twelve Months
Secondary outcomes:
measure: Adverse Event Rate
timeFrame: Twelve Months
measure: Serious Adverse Event Rate
timeFrame: Twelve Months
measure: Adherence to Protocol
timeFrame: Twelve Months
measure: Data Collection and Monitoring
timeFrame: Twelve Months
Other outcomes:
Locations:
city: Lexington
country: United States
facility: University of Kentucky - Chandler Medical Center
state: Kentucky
Study officials:
affiliation: University of Kentucky Neurosurgery
name: Jared Wilcox, MD, PhD
role: PRINCIPAL_INVESTIGATOR
References: