Electrical Neuromodulation for Spasticity

Recruiting at 1 trial location

Overseen By Dobrivoje S Stokic, MD, DSc

Age: 18+

Sex: Any

Trial Phase: Academic

Sponsor: University of Mississippi Medical Center

Disqualifiers: Neurological level below T11, Pregnancy, 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: Unknown

Duration: 4 weeks

12 Participants Needed

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial tests a new approach to manage spasticity, a condition where muscles tighten and spasm, often after a spinal cord injury (SCI). Researchers are exploring how different frequencies and intensities of electrical stimulation on the spine, known as electrical neuromodulation, can help reduce these muscle issues. Participants will try four different electrical stimulation methods to determine which best improves muscle control and comfort. This trial suits individuals who have had a spinal cord injury for more than a year and experience muscle spasticity in their lower limbs. As an unphased trial, this study offers a unique opportunity to contribute to innovative research that could improve future treatments for spasticity.

Will I have to stop taking my current medications?

The trial information does not specify whether you need to stop taking your current medications. It's best to discuss this with the study team or your doctor.

What prior data suggests that this electrical neuromodulation is safe for managing spasticity after spinal cord injury?

Research shows that transcutaneous spinal stimulation (TSS) is generally safe and well-tolerated for people with spinal cord injuries (SCI). TSS is a non-invasive technique where mild electrical stimulation is applied to the skin over the spine. Studies have found that it can help manage muscle tightness and spasms, known as spasticity. Importantly, these studies indicate that TSS is safe for people with long-term SCI, as it usually does not cause serious side effects.

Past research has used TSS alongside other treatments and found it to be safe and practical. Most participants did not experience significant negative effects, suggesting that the treatment is well-tolerated. While there might be some mild side effects, they are generally not serious or long-lasting.

Overall, although more research is needed to fully understand all possible effects, current evidence suggests that TSS is a safe option for managing spasticity in people with SCI. ^{1 2 3 4 5}

Why are researchers excited about this trial?

Researchers are excited about electrical neuromodulation for spasticity because it offers a non-invasive alternative to current treatments like oral medications and injections. Unlike traditional options that target symptoms through chemical means, this treatment uses electrical currents to stimulate the spinal cord, potentially providing more direct relief from muscle stiffness. The trial explores different frequencies and intensities of stimulation, potentially offering customizable treatment options for different patient needs. This approach could lead to more precise and effective management of spasticity with fewer side effects.

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

This trial will explore different approaches to electrical neuromodulation for spasticity. Research has shown that electrical treatments like transcutaneous spinal stimulation (TSS) can help with muscle stiffness and spasms after a spinal cord injury. Studies have found that TSS safely and effectively reduces these symptoms. For instance, using TSS at higher frequencies, such as 100 Hz, significantly lowered spasticity scores compared to other treatments. In this trial, participants will receive TSS at varying frequencies and intensities, such as 50 Hz or 100 Hz, and at high or low intensities. Overall, TSS might offer a non-drug option to manage spasticity and improve the quality of life for people with spinal cord injuries. ^{2 4 6 7 8}

Who Is on the Research Team?

Matthias J Krenn, PhD

Principal Investigator

University of Mississippi Medical Center

Are You a Good Fit for This Trial?

This trial is for adults over 18 with chronic spinal cord injury (SCI) who experience mild to severe spasticity in their lower limbs. Candidates should be at least six months post-injury and able to follow instructions, with no ongoing infections, pregnancy, or implanted devices that could interfere with the treatment.

Inclusion Criteria

I have a spinal cord injury graded A-D.

Signed consent form

I experience mild or greater leg spasticity, rating it above 3 out of 10.

Exclusion Criteria

You have a medical device implanted in your body that actively delivers medication.

I cannot have electrodes placed on my skin due to skin conditions.

I have implants like plates or screws between my T10 and L3 vertebrae.

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants receive transcutaneous spinal stimulation (TSS) for 30 minutes daily for six days with each of the four TSS protocols

4 weeks

Daily home-based sessions

Follow-up

Participants are monitored for safety and effectiveness after treatment, including focus group meetings to assess the experience with TSS as a home-based therapy

1 week

Focus group meeting

What Are the Treatments Tested in This Trial?

Interventions

• Electrical neuromodulation

Trial Overview The study tests four different protocols of transcutaneous spinal stimulation (TSS), a non-drug electrical neuromodulation therapy aimed at reducing muscle spasms caused by SCI. It's an experimental cross-over trial where participants will try each TSS protocol both immediately and as part of a home-based therapy routine.

How Is the Trial Designed?

Group I: Neuromodulation with 50 Hz and low intensity Experimental Treatment 1 Intervention

Transcutaneous spinal stimulation for 30 min with a stimulation frequency of 50 Hz and stimulation intensity of 0.45 x lowest motor threshold (reflex threshold in leg muscles).

Group II: Neuromodulation with 50 Hz and high intensity Experimental Treatment 1 Intervention

Transcutaneous spinal stimulation for 30 min with a stimulation frequency of 50 Hz and stimulation intensity of 0.90 x lowest motor threshold (reflex threshold in leg muscles).

Group III: Neuromodulation with 100 Hz and low intensity Experimental Treatment 1 Intervention

Transcutaneous spinal stimulation for 30 min with a stimulation frequency of 100 Hz and stimulation intensity of 0.45 x lowest motor threshold (reflex threshold in leg muscles).

Group IV: Neuromodulation with 100 Hz and high intensity Experimental Treatment 1 Intervention

Transcutaneous spinal stimulation for 30 min with a stimulation frequency of 100 Hz and stimulation intensity of 0.90 x lowest motor threshold (reflex threshold in leg muscles).

Electrical neuromodulation is already approved in United States, European Union for the following indications:

Approved in United States as Transcutaneous Spinal Stimulation for:

• Spasticity in spinal cord injury
• Upper limb function improvement in spinal cord injury

Approved in European Union as Transcutaneous Spinal Stimulation for:

• Spasticity in spinal cord injury
• Motor function improvement in spinal cord injury

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+

Published Research Related to This Trial

Both transcutaneous electrical nerve stimulation (TENS) and functional electrical stimulation (FES) significantly reduced lower limb spasticity in patients with spinal cord injury for up to 4 hours after a single session, indicating their potential as effective treatments.

While there were no significant differences between TENS and FES in overall effectiveness, FES may provide better outcomes for patients with spastic reflexes, suggesting it could be particularly beneficial for certain individuals.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Comparison of transcutaneous electrical nerve stimulation (TENS) and functional electrical stimulation (FES) for spasticity in spinal cord injury - A pilot randomized cross-over trial. Sivaramakrishnan, A., Solomon, JM., Manikandan, N.[2022]

Transcutaneous spinal cord stimulation (SCS) significantly reduced spasticity in 12 individuals with spinal cord injury, showing immediate and lasting effects on measures like the Modified Ashworth Scale and clonus after a single 30-minute session.

A follow-up study over 6 weeks indicated that self-administered transcutaneous SCS could lead to progressive improvements in spasticity, suggesting it may be an effective non-invasive treatment option for managing spasticity in patients with spinal cord injuries.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Transcutaneous Spinal Cord Stimulation Induces Temporary Attenuation of Spasticity in Individuals with Spinal Cord Injury. Hofstoetter, US., Freundl, B., Danner, SM., et al.[2021]

In a study involving six spinal cord injured patients, transcutaneous electrical nerve stimulation (TENS) was applied to target spastic muscles, resulting in a significant reduction of spasticity in three patients.

The effectiveness of TENS varied among individuals, indicating that while it can be beneficial for some, it may not work for everyone with spasticity.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Electrical stimulation in treating spasticity resulting from spinal cord injury. Bajd, T., Gregoric, M., Vodovnik, L., et al.[2006]

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]

Transcutaneous spinal stimulation (TSS) and whole-body vibration (WBV) are both effective non-pharmacological methods for managing spasticity in individuals with spinal cord injury, as shown in a study with 32 participants.

While neither TSS nor WBV showed significant differences in overall effectiveness, TSS was particularly beneficial for participants with more severe spasticity, leading to immediate and lasting reductions in spasticity after treatment.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Efficacy of Transcutaneous Spinal Stimulation versus Whole Body Vibration for Spasticity Reduction in Persons with Spinal Cord Injury. Sandler, EB., Condon, K., Field-Fote, EC.[2021]

Transcutaneous electrical nerve stimulation (TENS) is recommended as a low-cost and safe treatment for spasticity in patients with neurological conditions, based on a review of 10 studies involving 330 patients with conditions like stroke, multiple sclerosis, and spinal cord injuries.

Despite its potential benefits, the variability in stimulation parameters across studies makes it challenging to determine the most effective settings for TENS, highlighting the need for further research to optimize its use.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Transcutaneous electrical nerve stimulation for spasticity: A systematic review. Fernández-Tenorio, E., Serrano-Muñoz, D., Avendaño-Coy, J., et al.[2021]

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]

Transcutaneous spinal cord stimulation (TSS) significantly affects brain activity, activating key areas related to movement control and planning, as shown by EEG analysis in five participants performing lower-limb tasks.

TSS resulted in notable changes in functional connectivity in the brain during stimulation, unlike functional electrical stimulation (FES), suggesting TSS may be more effective for enhancing cortical engagement in rehabilitation strategies for spinal cord injury.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Effects of transcutaneous spinal stimulation on spatiotemporal cortical activation patterns: a proof-of-concept EEG study. Steele, AG., Manson, GA., Horner, PJ., 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]

Transcutaneous electrical stimulation in 44 patients with spinal cord injuries significantly reduced spasticity and improved both passive and active movement, as well as respiratory function.

The treatment also restored normal blood pressure and neurogenic bladder functions, indicating a broad range of benefits beyond just spasticity reduction.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Treatment of spinal spasticity by electrical stimulation. Franek, A., Turczynski, B., Opara, J.[2019]

Citations

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

Protocol for a Systematic Review and Meta-Analysis - PMC This systematic review and meta-analysis will determine the effectiveness of tSCS, compared with sham stimulation, no intervention, or other ...

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

Safety and Effectiveness of Multisite Transcutaneous ... This study showed that tSCS combined with ABT is safe, feasible, and effective in adults with chronic SCI ranging from the cervical to thoracic level when ...

3. frontiersin.org frontiersin.org/journals/rehabilitation-sciences/articles/10.3389/fresc.2022.1058663/full

Neurophysiological and clinical outcome measures of the ... Quantitative synthesis of non-RCT studies revealed that 22 of the 29 studies reported improvement in at least one measure of spasticity ...

4. jneuroengrehab.biomedcentral.com jneuroengrehab.biomedcentral.com/articles/10.1186/s12984-025-01744-3

Superior efficacy of 100-Hz transcutaneous electrical nerve ... As illustrated in Fig. 3, the meta-analysis demonstrated that TENS significantly reduced spasticity scores compared to control interventions.

5. nature.com nature.com/articles/s41393-022-00776-z

Efficacy of transcutaneous electrical nerve stimulation in ... This modality effectively increases blood circulation in the active area and improves pain [7, 8]. Clinically, it can be used to treat different ...

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

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

7. nature.com nature.com/articles/s41591-024-02940-9

Non-invasive spinal cord electrical stimulation for arm and ... These results demonstrate the safety and efficacy of ARC EX Therapy to improve hand and arm functions in people living with cervical SCI.

8. researchprotocols.org researchprotocols.org/2025/1/e80995/PDF

Effectiveness of Transcutaneous Spinal Cord Stimulation ... Secondary outcomes will include walking ability, balance, functional independence, spasticity, quality of life, and adverse events. Two ...