Neuromodulation for Muscle Stiffness After Spinal Cord Injury

Recruiting at 1 trial location

Overseen By Dobrivoje S Stokic, M.D., D.Sc.

Age: 18+

Sex: Any

Trial Phase: Phase < 1

Sponsor: University of Mississippi Medical Center

Must not be taking: Antibiotics, Botulinum toxin

Disqualifiers: Ventilatory-dependent, Pregnancy, Neurological changes, others

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

Approved in 2 Jurisdictions This treatment is already approved in other countries

Compensation: Varies

Number of Visits: 7

Duration: 3 to 5 weeks

16 Participants Needed

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial aims to determine if a non-surgical treatment called transcutaneous spinal stimulation (TSS or non-invasive spinal stimulation) can reduce muscle stiffness and spasms in individuals with spinal cord injuries. The study will test various levels of electrical stimulation applied via skin electrodes and compare them to standard muscle relaxant medications like baclofen and tizanidine. Researchers aim to discover if this new method, alone or combined with medication, can improve symptoms more effectively than current treatments. Individuals who have had a spinal cord injury for over six months and experience significant muscle tightness in their lower limbs may be suitable candidates for this trial. As an Early Phase 1 trial, this research focuses on understanding how the treatment works in people, offering participants a chance to be among the first to experience this innovative approach.

Will I have to stop taking my current medications?

The trial does not clearly state if you must stop taking your current medications, but it mentions that you may need to agree to reduce antispastic medication (medication for muscle stiffness and spasms) if needed.

What prior data suggests that transcutaneous spinal stimulation is safe for people with spinal cord injuries?

Research has shown that transcutaneous spinal stimulation is generally safe for people. This non-surgical method uses gentle electrical currents applied through electrodes on the skin and is well-tolerated. For instance, one study found that using this technique in children had similar safety results to a placebo, with no major side effects reported.

Additionally, other research combining this stimulation with physical therapy demonstrated improvements in movement without significant negative effects. These findings suggest the treatment is safe for people, although individual experiences may differ. ^{1 2 3 4 5}

Why are researchers excited about this trial's treatments?

Researchers are excited about transcutaneous spinal stimulation for muscle stiffness after spinal cord injury because it offers a novel approach to managing this challenging condition. Unlike traditional treatments like oral medications, which primarily address symptoms through pharmacological means, this technique delivers electrical currents directly through the skin to modulate spinal cord activity. This method has the potential to provide more targeted relief with fewer systemic side effects. Furthermore, when combined with medications like baclofen or tizanidine, transcutaneous spinal stimulation might enhance the overall therapeutic effect, offering a promising new avenue for individuals experiencing muscle stiffness after a spinal cord injury.

What evidence suggests that transcutaneous spinal stimulation is effective for reducing muscle stiffness after spinal cord injury?

Research shows that transcutaneous spinal stimulation (tSCS) can reduce muscle stiffness and spasms in people with spinal cord injuries. Studies have found that tSCS improves movement and lessens muscle tightness both immediately and over time. Evidence suggests it is safe and well-tolerated for those with long-term spinal cord injuries. In this trial, participants will receive various combinations of tSCS with baclofen, tizanidine, or a placebo to evaluate its effectiveness. Although researchers are still studying the treatment, early results are promising for relieving symptoms like muscle spasms. ^{1 2 6 7 8}

Who Is on the Research Team?

Matthias J Krenn, Ph.D.

Principal Investigator

University of Mississippi Medical Center

Are You a Good Fit for This Trial?

This trial is for individuals with spinal cord injuries experiencing muscle spasms and stiffness. Participants should be adults who have had a stable injury for at least six months. Specific criteria about the severity of the injury or other health conditions are not provided.

Inclusion Criteria

Agreement to reduce antispastic medication if needed

I have had a spinal cord injury in the past.

I was diagnosed with my condition more than six months ago.

Exclusion Criteria

Skin conditions precluding placement of electrodes

Pregnancy

My neurological condition has changed in the last 2 months.

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

1 week

1 visit (in-person)

Treatment

Participants receive transcutaneous spinal stimulation and study medication over six visits

3 to 5 weeks

6 visits (in-person)

Follow-up

Participants are monitored for changes in muscle stiffness and spasms after treatment

4 weeks

What Are the Treatments Tested in This Trial?

Interventions

• Transcutaneous Spinal Stimulation

Trial Overview The study tests transcutaneous spinal stimulation at different pulse rates (50 Hz, 100 Hz) and compares it to sham stimulation and common muscle relaxants (baclofen, tizanidine). The goal is to see if this non-invasive method can reduce muscle problems caused by spinal cord injuries.

How Is the Trial Designed?

Group I: Transcutaneous spinal stimulation in combination of baclofen/tizanidine/placebo Experimental Treatment 5 Interventions

Each participant will receive five distinct interventions: * Transcutaneous spinal stimulation at 100 Hz for 30 minutes with a placebo * Transcutaneous spinal stimulation at 50 Hz for 30 minutes with a placebo * Transcutaneous spinal stimulation at 50 Hz for 30 minutes with a single-dose baclofen * Transcutaneous spinal stimulation at 50 Hz for 30 minutes with a single-dose tizanidine * Transcutaneous spinal stimulation (sham) for 30 minutes with a placebo

Transcutaneous Spinal Stimulation is already approved in United States, European Union for the following indications:

Approved in United States as Transcutaneous Spinal Stimulation for:

• Spinal cord injury rehabilitation
• Improvement of walking function
• Reduction of spasticity

Approved in European Union as Transcutaneous Spinal Stimulation for:

• Spinal cord injury rehabilitation
• Improvement of walking function
• Reduction of spasticity

Who Is Running the Clinical Trial?

University of Mississippi Medical Center

Lead Sponsor

Trials

185

Recruited

200,000+

Methodist Rehabilitation Center

Collaborator

Trials

7

Recruited

170+

The Craig H. Neilsen Foundation

Collaborator

Trials

62

Recruited

3,100+

Published Research Related to This Trial

Repeated noninvasive transspinal stimulation significantly increased motoneuron output in both knee and ankle muscles of individuals with chronic spinal cord injury (SCI), suggesting it can enhance motor function recovery.

The study involved 20 participants (10 with SCI and 10 healthy controls) and demonstrated that this neuromodulation technique promotes spinal motoneuron responsiveness, indicating its potential for functional neuroplasticity after SCI.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Transspinal stimulation increases motoneuron output of multiple segments in human spinal cord injury. Murray, LM., Knikou, M.[2023]

In a study involving nine individuals with chronic spinal cord injury (SCI), both transcutaneous spinal stimulation (TSS) and epidural spinal stimulation (ESS) were found to activate lower-extremity muscles similarly when participants were relaxed, indicating potential for restoring motor function.

However, when participants attempted to contract their leg muscles, both TSS and ESS led to significant inhibition of muscle responses, suggesting that spinal stimulation may enhance inhibitory pathways in the spinal cord, which could be important for developing rehabilitation strategies for regaining motor function.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Voluntary Modulation of Evoked Responses Generated by Epidural and Transcutaneous Spinal Stimulation in Humans with Spinal Cord Injury. Calvert, JS., Gill, ML., Linde, MB., et al.[2022]

Cervical transcutaneous spinal cord stimulation (tSCS) can effectively activate sensory fibers at lower stimulation intensities when the cathode electrode is positioned at the C7 or T1 vertebra, compared to C6, which may enhance rehabilitation outcomes for upper-limb motor recovery after spinal cord injury.

Using smaller electrode sizes not only lowers the activation threshold for sensory fibers but also optimizes the recruitment of these fibers before α-motor fibers, suggesting a strategic approach to improve hand muscle activation during tSCS therapy.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Optimizing sensory fiber activation during cervical transcutaneous spinal stimulation using different electrode configurations: A computational analysis. de Freitas, RM., Capogrosso, M., Nomura, T., et al.[2022]

Epidural electrical stimulation and transcutaneous spinal cord stimulation (SCS) both effectively activate similar neural pathways in the lumbar spinal cord, as evidenced by comparable electromyographic (EMG) responses in individuals with spinal cord injury (SCI).

The study confirmed that both stimulation techniques produce similar muscle responses, supporting the idea that transcutaneous SCS can be a noninvasive alternative to epidural stimulation for enhancing motor function in SCI patients.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Common neural structures activated by epidural and transcutaneous lumbar spinal cord stimulation: Elicitation of posterior root-muscle reflexes. Hofstoetter, US., Freundl, B., Binder, H., et al.[2019]

Transspinal stimulation (TSS) is a promising non-invasive neuromodulation technique that can activate spinal cord circuits to improve motor function in individuals with spinal cord injury, as evidenced by a review of 34 studies.

The review highlighted that multisite electrode placements generally resulted in better motor responses compared to single-site placements, suggesting that optimizing stimulation parameters is crucial for enhancing treatment outcomes, although further controlled studies are needed.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Optimization of Transspinal Stimulation Applications for Motor Recovery after Spinal Cord Injury: Scoping Review. Rehman, MU., Sneed, D., Sutor, TW., et al.[2023]

Noninvasive transcutaneous spinal cord stimulation (tSCS) has been shown to effectively induce muscle activation in individuals with spinal cord injury, based on a systematic review of 13 studies involving 55 participants.

While tSCS appears to enhance voluntary movement, muscle strength, and function, further research is needed to determine the optimal electrode placement and current intensity for maximum efficacy.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Transcutaneous Spinal Cord Stimulation and Motor Rehabilitation in Spinal Cord Injury: A Systematic Review. Megía García, A., Serrano-Muñoz, D., Taylor, J., et al.[2021]

A novel noninvasive stimulation strategy combined with pharmacological intervention successfully re-engaged spinal locomotor networks in individuals with motor complete paralysis, enabling locomotor-like stepping without voluntary effort during a single session.

After 18 weeks of treatment, all five subjects showed significant improvements in voluntary motor control, with evidence of re-established functional connectivity between the brain and spinal cord, allowing for selective muscle activation.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Noninvasive Reactivation of Motor Descending Control after Paralysis. Gerasimenko, YP., Lu, DC., Modaber, M., et al.[2018]

Transcutaneous electrical spinal stimulation (TSS) can effectively modulate interlimb sensorimotor function, showing bidirectional influences on motor output from cervical and lumbosacral regions in a study involving 16 participants.

The study found that TSS can facilitate spinally evoked motor responses in both arm and leg muscles, indicating its potential as a therapeutic approach for enhancing recovery in individuals with compromised motor function after neurological injuries.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Characterization of interlimb interaction via transcutaneous spinal stimulation of cervical and lumbar spinal enlargements. Atkinson, DA., Steele, AG., Manson, GA., et al.[2023]

In a study with 10 healthy participants, transcutaneous spinal stimulation (TSS) using a 5 kHz carrier frequency was tolerated better than conventional stimulation methods, allowing for higher stimulation levels without discomfort.

Despite the improved tolerance with the carrier frequency, when comparing the intensity needed to evoke muscle responses, all stimulation paradigms were equally effective, indicating that discomfort reduction does not enhance the efficacy of TSS in eliciting motor responses.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

The relationship between maximum tolerance and motor activation during transcutaneous spinal stimulation is unaffected by the carrier frequency or vibration. Manson, GA., Calvert, JS., Ling, J., et al.[2021]

In a study involving eight participants with tetraplegia due to cervical spinal cord injury, transcutaneous spinal stimulation (TSS) revealed that upper limb muscles below the injury site had reduced sensitivity to stimulation compared to those above the lesion.

The results suggest that TSS can provide valuable electrophysiological data that helps assess the extent of functional asymmetry and disruptions in neural pathways, potentially enhancing clinical evaluations of motor function in individuals with spinal cord injuries.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Transcutaneous spinal stimulation provides characterization of neurological status in individuals with tetraplegia. Oh, J., Scheffler, MS., Martin, CA., et al.[2023]

Transcutaneous spinal cord stimulation (tSCS) shows potential for generating motor activity in individuals with spinal cord injury, but the overall quality of the studies reviewed was poor-to-fair, indicating a need for more rigorous research.

The review identified significant variability in stimulation parameters and outcome measurements across the 25 studies analyzed, highlighting the necessity for standardized methods to improve the reliability and comparability of tSCS research.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Transcutaneous spinal cord stimulation and motor responses in individuals with spinal cord injury: A methodological review. Taylor, C., McHugh, C., Mockler, D., et al.[2022]

Citations

1. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC10274551/

Transcutaneous spinal cord stimulation effects on spasticity ... TSCS appears safe and well-tolerated intervention in patients with SCI. The evidence for the effectiveness of tSCS on spasticity in chronic SCI patients is ...

2. 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 ...

3. 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 ...

4. clinicaltrials.gov clinicaltrials.gov/study/NCT03509558

Transcutaneous Spinal Stimulation and Exercise for ... Growing evidence indicates that electrical spinal cord stimulation improves motor functions both immediately and over the long term via modulating the ...

5. physoc.onlinelibrary.wiley.com physoc.onlinelibrary.wiley.com/doi/full/10.1113/JP287100

Transcutaneous spinal cord stimulation at alternating ... Transcutaneous spinal cord stimulation (tSCS) has shown potential for targeting and improving spasticity after spinal cord injury (SCI) in both ...

6. clinicaltrials.gov clinicaltrials.gov/study/NCT03975634

Transcutaneous Spinal Stimulation: Safety and Feasibility ... Activity-based locomotor training has resulted in improved trunk control in children with spinal cord injury, though full recovery is not achieved in all ...

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

Transcutaneous Electrical Spinal Cord Stimulation to ... Objective: To evaluate the impact of using transcutaneous electrical spinal cord stimulation (TSCSTSCS) on upper and lower extremity ...

8. hopkinsmedicine.org hopkinsmedicine.org/clinical-trials/results/irb00300695

Transcutaneous spinal stimulation (TSS) in children with ... Administration of TSCS to children in a clinical setting will be safe based on similar safety outcomes as sham TSCS.