Spinal Cord Stimulation + Training for Spinal Cord Injury

Overseen By Gail Forrest, PhD

Age: 18+

Sex: Any

Trial Phase: Academic

Sponsor: Kessler Foundation

Must not be taking: Anti-spasticity medications

Disqualifiers: Seizures, Head trauma, Cognitive deficit, others

No Placebo Group All trial participants will receive the active study treatment (no placebo)

Compensation: Varies

Number of Visits: 13

Duration: 2 weeks

30 Participants Needed

Trial Summary

What is the purpose of this trial?

The purpose of this clinical trial is to understand the safety and practicality of using spinal cord transcutaneous (through the skin) stimulation in an inpatient setting as well as how the combination of activity-based training (ABT) and spinal cord transcutaneous stimulation (scTS) can improve participants' ability to use their hands, arms, and trunk in an inpatient rehabilitation program. The main questions it aims to answer are: * Is the combination of spinal cord transcutaneous stimulation and ABT is safe and practical when applied to individuals with acute to subacute cervical SCI during inpatient rehabilitation? * How the combined intervention can improve hand and arm function when applied to those individuals? The investigators will assess the safety, feasibility, and preliminary efficacy of the combined intervention and compare to a sham control (sham stimulation combined with ABT) and a ABT only group to see if the combined intervention can lead to greater function recovery. Participants will: * Receive one type of the three intervention (scTS+ABT, sham scTS+ABT, or ABT only) for 10 sessions with 30 mins/session over 2 weeks. * Receive assessment before, during, and immediately after the intervention, and at 1-month, 2-month, and 3-month follow-up visits.

Will I have to stop taking my current medications?

The trial requires participants to stop taking anti-spasticity medications (like baclofen, Xeomin, and Lioresal) if they are unable or unwilling to wean off them.

What data supports the effectiveness of the treatment Spinal Cord Stimulation + Training for Spinal Cord Injury?

Research shows that combining spinal cord transcutaneous stimulation with activity-based training can improve walking and upper extremity function in people with spinal cord injuries. Studies found that this combination led to significant improvements in walking speed and distance, as well as upper limb strength and sensation, suggesting it helps restore motor and sensory functions. ^{1 2 3 4 5}

Is spinal cord stimulation safe for humans?

Spinal cord stimulation, including transcutaneous methods, has been studied in humans and is generally considered safe. In a study with participants who had spinal cord injuries, the treatment was found to be feasible and tolerable, with no significant safety concerns reported. ^{2 5 6 7 8}

How is the treatment of Spinal Cord Stimulation + Training for Spinal Cord Injury different from other treatments?

This treatment is unique because it combines activity-based training with spinal cord transcutaneous stimulation, a non-invasive method that enhances the excitability of spinal circuits to improve motor and sensory functions. Unlike other treatments, it can lead to persistent recovery of function and has both excitatory effects at the spinal level and inhibitory effects at the cortical level, promoting long-term rehabilitation benefits. ^{1 9 10 11 12}

Research Team

Gail Forrest, PhD

Principal Investigator

Kessler Foundation

Eligibility Criteria

This trial is for individuals with recent cervical spinal cord injuries who are currently in an inpatient rehabilitation program. It's designed to see if a combination of skin-level spinal stimulation and activity-based training can help improve the use of their hands, arms, and trunk.

Inclusion Criteria

I can understand and am willing to sign the informed consent.

My spinal cord injury is in the neck area and is severe.

I am medically fit to engage in physical recovery activities.

Exclusion Criteria

Unable to meet the attendance requirements

Currently enrolled in another interventional research study

I struggle to stay alert or follow instructions during medical assessments.

Timeline

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants receive one of the three interventions (scTS+ABT, sham scTS+ABT, or ABT only) for 10 sessions over 2 weeks.

2 weeks

10 sessions (in-person)

Follow-up

Participants are monitored for safety and effectiveness after treatment with assessments at 1-month, 2-month, and 3-month follow-up visits.

3 months

3 visits (in-person)

Treatment Details

Interventions

• Activity-based Training
• Spinal Cord Transcutaneous Stimulation

Trial Overview The study tests three different interventions: actual spinal stimulation combined with training (scTS+ABT), fake stimulation with training (sham scTS+ABT), and just the training on its own (ABT only). Participants will be randomly assigned to one group for ten sessions over two weeks.

Participant Groups

Group I: Activity-based Training Only Experimental Treatment 1 Intervention

Participants in ABT group will receive ABT only. ABT will concentrate on activities of gross UE movement, grasping, pinching, gross and fine motor skill. The hand grasp task will focus on grasping objects with different shapes and weights (i.e. weighted container and tennis ball) and placing/removing them from small storage container; the pinch task involves picking up, translating, and releasing small objects with varied sizes (i.e. blocks, dices, marble balls, nuts, etc.). The training therapist selects tasks based on participant's level of impairment and individual goals. The dosage of ABT will be 30 minutes/session, with approximately 15 minutes allocated on each side.

Group II: Active Spinal Cord Transcutaneous Stimulation Combined with Activity-based Training Active Control 1 Intervention

Participants will receive activity-based training (ABT) while receiving concomitant, active spinal stimulation (scTS) applied at the cervical and thoracic spinal segments over the dorsal skin with optimized and customized stimulation parameters. Round self-adhesive electrodes will be placed over the skin at the midline of spinous processes as cathodes and a pair of rectangular anodes electrodes will be placed over the anterior iliac crests of the pelvis. The stimulation waveform is rectangular pulse with 1-ms duration filled with a carrier frequency of 5kHz. Target simulation will be sub-threshold for UE muscle activation and verified by the absence of visible muscle contraction. The stimulation parameters will be adjusted as needed throughout the intervention course based on the participant's performance and comfort level. The intervention will be administered over 2 consecutive weeks, for 30mins/session and 5 sessions/week, as a part of their daily 3-hour therapy.

Group III: Sham Spinal Cord Transcutaneous Stimulation Combined with Activity-based Training Placebo Group 1 Intervention

The sham-control group will go through ABT paired with sham stimulation to control for placebo effects associated with the perception of scTS. Stimulation will be delivered at one cervical location. No stimulation mapping procedure will be performed. During the training session, the stimulation intensity will be briefly ramped up to a level at which the participants report perceiving the stimulation, and then ramped down to 0mA at both the start and the end of session. The stimulator and electrodes will remain attached to the participant while receiving ABT training. The intervention will be administered over 2 consecutive weeks, for 30mins/session and 5 sessions/week, as a part of their daily 3-hour therapy.

Who Is Running the Clinical Trial?

Kessler Foundation

Lead Sponsor

Trials

190

Recruited

11,300+

Findings from Research

Targeted transcutaneous spinal cord stimulation (tSCS) in two individuals with motor-complete spinal cord injury led to a remarkable increase in exerted force by up to 1,136% when combined with weekly activity-based training.

This study is the first to report a significant improvement in tactile sensation, with a 2-point increase in clinical assessments, and the benefits persisted for at least one month after stimulation, indicating potential for lasting recovery of motor and sensory functions.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Targeted transcutaneous spinal cord stimulation promotes persistent recovery of upper limb strength and tactile sensation in spinal cord injury: a pilot study. Chandrasekaran, S., Bhagat, NA., Ramdeo, R., et al.[2023]

In a study involving 18 individuals with subacute motor-incomplete spinal cord injury, combining locomotor training (LT) with transcutaneous spinal stimulation (TSS) showed promising improvements in walking speed and distance after a 4-week program, although no significant differences were found between the TSS and sham groups.

The results suggest that TSS is a feasible addition to LT during rehabilitation, potentially enhancing walking outcomes, but did not significantly affect spasticity, possibly due to high variability in spasticity measurements.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Combined Transcutaneous Spinal Stimulation and Locomotor Training to Improve Walking Function and Reduce Spasticity in Subacute Spinal Cord Injury: A Randomized Study of Clinical Feasibility and Efficacy. Estes, S., Zarkou, A., Hope, JM., et al.[2022]

In a pilot study involving 7 individuals with chronic spinal cord injury, the use of transcutaneous electrical spinal cord stimulation (TSCS) combined with functional training led to improvements in upper and lower extremity function, with all participants showing progress on the Capabilities of Upper Extremity Test (CUE-T).

Notably, two participants improved their ASIA impairment scale classification, and five individuals experienced enhanced sensation, demonstrating that TSCS can facilitate recovery even after a plateau in rehabilitation progress, without any serious adverse events.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Transcutaneous Electrical Spinal Cord Stimulation to Promote Recovery in Chronic Spinal Cord Injury. Tefertiller, C., Rozwod, M., VandeGriend, E., et al.[2022]

A case study of a 27-year-old male with chronic spinal cord injury showed that combining locomotor training with multi-segmental spinal cord transcutaneous electrical stimulation (scTS) can enhance recovery of locomotion by reactivating dormant spinal networks.

After a 3-month training regimen, improvements in stepping coordination were observed, indicating that scTS may facilitate neuroplastic changes and better sensory-motor integration, which are crucial for functional recovery.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Novel Noninvasive Spinal Neuromodulation Strategy Facilitates Recovery of Stepping after Motor Complete Paraplegia. Siu, R., Brown, EH., Mesbah, S., et al.[2022]

A multicenter randomized clinical trial is investigating the effectiveness of combining spinal cord transcutaneous stimulation (scTS) with activity-based training (ABT) for improving upper extremity function in individuals with cervical spinal cord injury, showing promising preliminary results.

In a small sample of four participants, the combination of scTS and ABT led to immediate and sustained improvements in upper extremity function, with one participant experiencing a remarkable 5-fold increase in function, indicating potential for significant rehabilitation benefits.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Combining Spinal Cord Transcutaneous Stimulation with Activity-based Training to Improve Upper Extremity Function Following Cervical Spinal Cord Injury. Zhang, F., Carnahan, J., Ravi, M., et al.[2023]

Only 30% of the 40 reviewed clinical trials on acute spinal cord injury provided satisfactory reporting of adverse events, indicating a significant gap in safety information that is crucial for assessing risk and designing future studies.

A staggering 82.5% of trials failed to report laboratory-defined toxicity satisfactorily, highlighting the need for improved standards in safety reporting to ensure comprehensive understanding of treatment risks.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

A Systematic Review of Safety Reporting in Acute Spinal Cord Injury Clinical Trials: Challenges and Recommendations. Aspinall, P., Harrison, L., Scheuren, P., et al.[2023]

In a study involving 122 participants with chronic low back and/or leg pain, multiphase spinal cord stimulation (SCS) significantly reduced pain levels, with mean reductions of -4.3 and -4.7 on the numerical rating scale for two different multiphase therapies.

The multiphase SCS therapies were found to be safe, with only one non-serious device-related adverse event reported and no infections, suggesting a favorable safety profile for this new stimulation paradigm.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Multiphase Spinal Cord Stimulation in Participants With Chronic Back or Leg Pain: Results of the BENEFIT-02 Randomized Clinical Trial. Kapural, L., Patterson, DG., Li, S., et al.[2023]

A new animal model for transcutaneous spinal cord stimulation (tSCS) was developed, which accurately mimics human responses and allows for stable, repeated treatments after spinal cord injury (SCI) with minimal restraint.

The study demonstrated that tSCS can effectively modulate motor output in rats after complete spinal cord transection, suggesting its potential for promoting neuroplasticity and functional recovery in SCI.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Adapting Human-Based Transcutaneous Spinal Cord Stimulation to Develop a Clinically Relevant Animal Model. Malloy, DC., Knikou, M., Côté, MP.[2023]

Transvertebral spinal cord stimulation (SCS) was tested in rats and showed specific effects on muscle activation in the lower thoracic and lumbosacral spinal cord, indicating its potential for targeted neuromodulation after spinal cord injuries.

The study found that transvertebral SCS produced similar muscle activation patterns and neuroanatomical effects as traditional transcutaneous stimulation, suggesting it could be an effective alternative for recovery therapies.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Mapping of the Spinal Sensorimotor Network by Transvertebral and Transcutaneous Spinal Cord Stimulation. Shkorbatova, P., Lyakhovetskii, V., Pavlova, N., et al.[2020]

Transcutaneous electrical stimulation of the spinal cord (TESS) significantly enhances motor-evoked potentials in arm muscles for up to 75 minutes after stimulation, indicating its potential to promote functional recovery in individuals with spinal cord injury (SCI).

The study found that TESS has a dual effect: it excites spinal networks while inhibiting cortical activity, which may contribute to improved hand and arm function, especially when using a specific 5 kHz carrier frequency during stimulation.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Cortical and Subcortical Effects of Transcutaneous Spinal Cord Stimulation in Humans with Tetraplegia. Benavides, FD., Jo, HJ., Lundell, H., et al.[2021]

Spinal cord transcutaneous stimulation (scTS) has shown promise in enhancing recovery of motor, sensory, and autonomic functions after spinal cord injuries, but the specific mechanisms behind its effects are not fully understood.

Preliminary findings suggest that scTS-based motor training may differentially affect cortical connectivity and corticospinal excitability in both able-bodied individuals and those with spinal cord injuries, indicating a need for further research to optimize this intervention.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Differential Corticospinal Excitability and Cortical Functional Connectivity Modulation by Spinal Cord Transcutaneous Stimulation-based Motor Training versus Motor Training alone in Able-bodied and SCI participants: A Multiple Case Study. Brihmat, N., Bayram, MB., Ravi, M., et al.[2023]

Epidural spinal cord stimulation can activate spared neural circuitry below severe spinal cord injuries, enabling paralyzed individuals to achieve motor outputs like standing and stepping during assisted treadmill exercises.

This stimulation not only generates immediate motor responses but also supports rehabilitation by promoting long-term neural plasticity, potentially leading to lasting improvements in motor function for patients with spinal cord injuries.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Spinal Cord Stimulation and Augmentative Control Strategies for Leg Movement after Spinal Paralysis in Humans. Minassian, K., Hofstoetter, US.[2020]

References

1. Switzerland pubmed.ncbi.nlm.nih.gov

Targeted transcutaneous spinal cord stimulation promotes persistent recovery of upper limb strength and tactile sensation in spinal cord injury: a pilot study. [2023]

2. Switzerland pubmed.ncbi.nlm.nih.gov

Combined Transcutaneous Spinal Stimulation and Locomotor Training to Improve Walking Function and Reduce Spasticity in Subacute Spinal Cord Injury: A Randomized Study of Clinical Feasibility and Efficacy. [2022]

3. Switzerland pubmed.ncbi.nlm.nih.gov

Transcutaneous Electrical Spinal Cord Stimulation to Promote Recovery in Chronic Spinal Cord Injury. [2022]

4. Switzerland pubmed.ncbi.nlm.nih.gov

Novel Noninvasive Spinal Neuromodulation Strategy Facilitates Recovery of Stepping after Motor Complete Paraplegia. [2022]

5. United States pubmed.ncbi.nlm.nih.gov

Combining Spinal Cord Transcutaneous Stimulation with Activity-based Training to Improve Upper Extremity Function Following Cervical Spinal Cord Injury. [2023]

6. United States pubmed.ncbi.nlm.nih.gov

A Systematic Review of Safety Reporting in Acute Spinal Cord Injury Clinical Trials: Challenges and Recommendations. [2023]

7. United States pubmed.ncbi.nlm.nih.gov

Multiphase Spinal Cord Stimulation in Participants With Chronic Back or Leg Pain: Results of the BENEFIT-02 Randomized Clinical Trial. [2023]

8. Switzerland pubmed.ncbi.nlm.nih.gov

Adapting Human-Based Transcutaneous Spinal Cord Stimulation to Develop a Clinically Relevant Animal Model. [2023]

9. Switzerland pubmed.ncbi.nlm.nih.gov

Mapping of the Spinal Sensorimotor Network by Transvertebral and Transcutaneous Spinal Cord Stimulation. [2020]

10. United States pubmed.ncbi.nlm.nih.gov

Cortical and Subcortical Effects of Transcutaneous Spinal Cord Stimulation in Humans with Tetraplegia. [2021]

11. United States pubmed.ncbi.nlm.nih.gov

Differential Corticospinal Excitability and Cortical Functional Connectivity Modulation by Spinal Cord Transcutaneous Stimulation-based Motor Training versus Motor Training alone in Able-bodied and SCI participants: A Multiple Case Study. [2023]

12. England pubmed.ncbi.nlm.nih.gov

Spinal Cord Stimulation and Augmentative Control Strategies for Leg Movement after Spinal Paralysis in Humans. [2020]