Transspinal Stimulation + Locomotor Training for Spinal Cord Injury

No longer recruiting at 2 trial locations

Overseen By Noam Y Harel, MD PhD

Age: 18+

Sex: Any

Trial Phase: Academic

Sponsor: City University of New York

Must not be taking: Seizure threshold medications

Disqualifiers: Supraspinal lesions, Neuropathies, Pregnancy, others

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

Approved in 4 Jurisdictions This treatment is already approved in other countries

Compensation: Varies

Number of Visits: 40

Duration: Approximately 8-10 weeks

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial explores a method to help people with spinal cord injuries improve their ability to walk. It combines a special type of physical therapy called locomotor training with electrical spinal stimulation, which might boost recovery. Participants will receive either real or sham (inactive) stimulation before their therapy sessions. This study suits those with a motor-incomplete spinal cord injury, meaning they still have some movement or sensation below the injury. As an unphased trial, it offers participants the chance to contribute to groundbreaking research that could enhance rehabilitation methods for spinal cord injuries.

Will I have to stop taking my current medications?

The trial does not specify if you need to stop taking your current medications, but it excludes people taking medications that may change the seizure threshold. It's best to discuss your specific medications with the trial team.

What prior data suggests that transspinal stimulation and locomotor training are safe for spinal cord injury patients?

Research shows that transspinal stimulation is generally safe. Studies on similar treatments, such as transcutaneous spinal cord stimulation, indicate they are well-tolerated, with few side effects reported by users.

One study found that combining spinal stimulation with activity-based training improved movement in people with spinal cord injuries after several sessions. This suggests the treatment is not only effective but also safe over time. Another study reviewed spinal cord stimulation and found it to be safe, with few adverse effects.

While these findings are encouraging, it's important to remember that this specific trial's treatment is still under investigation. However, existing research suggests the treatment is likely safe for participants. ^{1 2 3 4 5}

Why are researchers excited about this trial?

Researchers are excited about these treatments because transspinal stimulation combined with locomotor training could offer new hope for people with spinal cord injuries. Unlike traditional therapies like physical therapy and conventional gait training, these methods involve delivering electrical stimulation to the spinal cord, either during standing or while lying down, to potentially enhance neural connections and promote movement. The addition of robotic gait training provides controlled, supportive movement, which might lead to improved recovery outcomes. This approach is particularly promising because it may help activate and strengthen neural pathways in a way that conventional methods do not, potentially leading to better mobility and independence for patients.

What evidence suggests that this trial's treatments could be effective for spinal cord injury?

Research has shown that transspinal stimulation could help people with spinal cord injuries regain movement. This trial will evaluate different approaches to transspinal stimulation. One group will receive real transspinal stimulation while standing, and another will receive it while lying supine. Both groups will follow this with locomotor training. A sham group will receive transspinal stimulation at an intensity where sensation is absent during standing, followed by locomotor training. This technique can activate important muscles, potentially improving movement and walking ability. When combined with other treatments, transspinal stimulation has helped people recover more function after a spinal cord injury. It is noninvasive, meaning it doesn't involve surgery, and studies have found it to be safe. Early results are promising, suggesting it could improve walking ability when used with walking training. ^{2 4 5 6 7}

Who Is on the Research Team?

Noam Y Harel, MD PhD

Principal Investigator

Bronx Veterans Medical Research Foundation

Maria Knikou, PT, PhD

Principal Investigator

Research Foundation of the City University of New York

Are You a Good Fit for This Trial?

This trial is for adults aged 18-70 with motor-incomplete spinal cord injury (SCI) above the T10 level, who can sign consent and commit to the study duration. They must be in good health, have a bone mineral density T-score <3.5 SD from norms, reflexes present for soleus H-reflex testing, flexible ankle joints without contractures, first-time SCI due to trauma or similar causes, and at least 6 months post-SCI.

Inclusion Criteria

You have had a spinal cord injury for more than 6 months.

In good general health as evidenced by medical history

You have had a spinal cord injury for more than 6 months.

Exclusion Criteria

I have a history of seizures.

I am not on medications that affect seizure risk.

I am not currently part of any research study or new rehab program.

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants undergo 40 sessions of body weight-supported step training primed with high-frequency transspinal stimulation

Approximately 8-10 weeks

40 sessions (in-person)

Follow-up

Participants are monitored for changes in spinal and corticospinal plasticity, ambulatory function, balance, and autonomic function

4 years

What Are the Treatments Tested in This Trial?

Interventions

• Robotic Gait Training
• Transspinal Stimulation

Trial Overview The study tests if high-frequency noninvasive thoracolumbar spinal stimulation before locomotor training improves walking ability in people with incomplete SCI. Participants will receive either real or sham stimulation while lying down or standing before robotic gait training over 40 sessions.

How Is the Trial Designed?

Group I: Real transspinal stimulation delivered while lying supine followed by locomotor training Experimental Treatment 1 Intervention

Transspinal tonic stimulation will be delivered at a frequency of 30 Hz while lying supine.

Group II: Real transspinal stimulation delivered during standing followed by locomotor training Experimental Treatment 1 Intervention

Transspinal tonic stimulation of the thoracolumbar region will be delivered at a frequency of 30 Hz during standing with as needed body weight support (BWS) in a standing frame or in the Lokomat to ensure safety.

Group III: Sham transspinal stimulation delivered during standing followed by locomotor training Placebo Group 1 Intervention

One sham group will be receiving transspinal stimulation during standing at an intensity where sensation is absent.

Robotic Gait Training is already approved in European Union, United States, Canada, Switzerland for the following indications:

Approved in European Union as Robotic Assisted Gait Training for:

• Spinal cord injury
• Cerebral palsy
• Stroke
• Multiple sclerosis
• Parkinson’s disease

Approved in United States as Robotic Assisted Gait Training for:

• Spinal cord injury
• Cerebral palsy
• Stroke
• Multiple sclerosis
• Parkinson’s disease

Approved in Canada as Robotic Assisted Gait Training for:

• Spinal cord injury
• Cerebral palsy
• Stroke
• Multiple sclerosis
• Parkinson’s disease

Approved in Switzerland as Robotic Assisted Gait Training for:

• Spinal cord injury
• Cerebral palsy
• Stroke
• Multiple sclerosis
• Parkinson’s disease

Who Is Running the Clinical Trial?

City University of New York

Lead Sponsor

Trials

23

Recruited

6,000+

Bronx Veterans Medical Research Foundation, Inc

Collaborator

Trials

10

Recruited

750+

Icahn School of Medicine at Mount Sinai

Collaborator

Trials

933

Recruited

579,000+

Published Research Related to This Trial

Combining robot-assisted rehabilitation (RAR) with non-invasive brain stimulation (NIBS) significantly improves lower extremity motor function in adults with incomplete spinal cord injury compared to RAR alone, as shown by greater improvements in tests like the 10 m walk test and the Functional Independence Measure-Locomotion.

No adverse effects were reported during the trial, indicating that the combined approach of RAR and NIBS is safe for participants, but further research with larger groups is needed to explore long-term benefits.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Finding the Way to Improve Motor Recovery of Patients with Spinal Cord Lesions: A Case-Control Pilot Study on a Novel Neuromodulation Approach. Naro, A., Billeri, L., Balletta, T., et al.[2023]

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]

Robot-assisted gait training (RAGT) significantly improves walking-related outcomes, such as gait distance and leg strength, in patients with incomplete spinal cord injury, especially during the acute phase of recovery, compared to over-ground training (OGT).

In chronic spinal cord injury patients, RAGT also enhances walking speed and balance more effectively than no intervention, suggesting it is a valuable rehabilitation technique for restoring mobility and promoting a healthier lifestyle.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Robot-assisted gait training (Lokomat) improves walking function and activity in people with spinal cord injury: a systematic review. Nam, KY., Kim, HJ., Kwon, BS., et al.[2020]

A new functional electrical stimulation (FES) system was developed that adapts stimulation timing based on the position of the hindlimb during stepping in a rodent model of spinal cord injury, which is an improvement over traditional fixed-timing FES systems.

This innovative system aims to enhance rehabilitation by promoting spinal plasticity, potentially leading to better recovery outcomes for individuals with spinal cord injuries.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

A system to integrate electrical stimulation with robotically controlled treadmill training to rehabilitate stepping after spinal cord injury. Chao, T., Askari, S., De Leon, R., et al.[2012]

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]

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]

A review of studies on robot-assisted gait training for spinal cord injury patients found that while some improvements in body functions were noted, the evidence is insufficient to conclude that this method is more effective than traditional locomotor training due to small sample sizes and methodological issues.

The analysis included 6 trials with 43 patients, primarily using devices like the Lokomat, but highlighted the need for better-designed randomized controlled trials to establish the efficacy of robot-assisted training in improving walking ability.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Effectiveness of robot-assisted gait training in persons with spinal cord injury: a systematic review. Swinnen, E., Duerinck, S., Baeyens, JP., et al.[2022]

In a study involving 15 spinal cord injury patients, overground robotic gait training (Ekso GT) required higher energy expenditure and cognitive effort compared to treadmill robotic training (Lokomat), indicating a more demanding rehabilitation process.

Despite the increased effort, both robotic systems were well-received by patients, with improvements in walking economy observed, suggesting that both methods can be effective in enhancing rehabilitation outcomes.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Energy cost and psychological impact of robotic-assisted gait training in people with spinal cord injury: effect of two different types of devices. Corbianco, S., Cavallini, G., Dini, M., et al.[2021]

In a study involving 12 patients with chronic spinal cord injury, both standard rehabilitation and robot-assisted gait training (RAGT) led to increased self-selected walking speed, indicating short-term efficacy in improving gait functions.

RAGT specifically contributed to a significant increase in step length, which was associated with improved hip flexor muscle function, highlighting its potential as a beneficial intervention in rehabilitation for SCI patients.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Gait training using a wearable robotic hip device for incomplete spinal cord injury: A preliminary study. Yoshikawa, K., Mutsuzaki, H., Koseki, K., et al.[2023]

Robotic gait training using the Robotic Exoskeleton Assisted Rehabilitation Systems (REARS) was found to be safe and feasible for individuals with incomplete motor spinal cord injury, with no reported injuries during the training sessions.

Participants who initially could not perform certain walking tests showed significant improvements after training, indicating enhanced balance and walking capacity, with some scores approaching clinically meaningful changes.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Gait Training with Robotic Exoskeleton Assisted Rehabilitation System in Patients with Incomplete Traumatic and Non-Traumatic Spinal Cord Injury: A Pilot Study and Review of Literature. Gupta, A., Prakash, NB., Honavar, PR.[2023]

A network meta-analysis of 12 studies involving 353 participants with spinal cord injury found that wearable exoskeleton-assisted walking (EAW) significantly improved walking distance and speed compared to Lokomat training.

While both Lokomat and EAW enhanced locomotor abilities, EAW showed a higher probability of improving walking speed, suggesting it may be a more effective option for enhancing locomotion in individuals with spinal cord injury.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Comparison of Efficacy of Lokomat and Wearable Exoskeleton-Assisted Gait Training in People With Spinal Cord Injury: A Systematic Review and Network Meta-Analysis. Zhang, L., Lin, F., Sun, L., et al.[2022]

In a study of nine individuals with chronic motor-incomplete spinal cord injury, continuous lumbosacral transcutaneous spinal stimulation (TSS) at varying frequencies showed diverse effects on robotic torques and muscle activity during robotic gait training.

The results indicated that higher stimulation frequencies generally led to greater changes in robotic torques and reduced muscle activity in some participants, while others exhibited increased muscle activity at mid-frequency ranges, highlighting the need for personalized approaches in TSS therapy for gait improvement.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Neuromodulation with transcutaneous spinal stimulation reveals different groups of motor profiles during robot-guided stepping in humans with incomplete spinal cord injury. Krenn, MJ., White, JM., Stokic, DS., et al.[2023]

Citations

1. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC12548825/

Protocol for a Systematic Review and Meta-Analysis - PMC Transcutaneous spinal cord stimulation (tSCS) has emerged as a promising neuromodulation technique for enhancing motor recovery and walking ...

2. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC10470322/

Spinal cord stimulation for spinal cord injury - PubMed Central Spinal cord stimulation at lower thoracic levels (T9-T11) results in triggering of key muscles and restoration of an effective cough. Enhanced cough and ...

3. clinicaltrials.gov clinicaltrials.gov/study/NCT04043715

Comparison of Transcutaneous and Epidural Spinal ... The purpose of this study is to determine the optimal method for delivering spinal stimulation to improve walking in people with incomplete spinal cord injury.

4. sciencedirect.com sciencedirect.com/science/article/pii/S1094715925000078

Safety and Effectiveness of Multisite Transcutaneous ... Combined tSCS + ABT facilitated functional recovery after chronic SCI. Improvements required ≥60 tSCS-ABT sessions, with further exposure to tSCS facilitating ...

5. frontiersin.org frontiersin.org/journals/rehabilitation-sciences/articles/10.3389/fresc.2021.740307/full

Transcutaneous Electrical Spinal Cord Stimulation to ... To evaluate the impact of using transcutaneous electrical spinal cord stimulation (TSCSTSCS) on upper and lower extremity function in individuals with chronic ...

6. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC8954138/

Trans-Spinal Electrical Stimulation Therapy for Functional ... Conventional treatment approaches aim to reduce secondary complications and improve the functions that have been retained after the injury [13].

7. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC10889415/

Epidural Spinal Cord Stimulation for Spinal Cord Injury in ... This study reviews the evolving role of epidural spinal cord stimulation (eSCS) in treating chronic SCI, focusing on its efficacy and safety.