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

Trial Summary

What is the purpose of this trial?

Spasticity develops months after spinal cord injury (SCI) and persists over time. It presents as a mixture of tonic features, namely increased muscle tone (hypertonia) and phasic features, such as hyperactive reflexes (hyperreflexia), clonus, and involuntary muscle contractions (spasms). Spasticity is often disabling because it interferes with hygiene, transfers, and locomotion and can disturb sleep and cause pain. For these reasons, most individuals seek treatments for spasticity after SCI. New developments in electrical neuromodulation with transcutaneous spinal stimulation (TSS) show promising results in managing spasticity non-pharmacologically. The underlying principle of TSS interventions is that the afferent input generated by posterior root stimulation modifies the excitability of the lumbosacral network to suppress pathophysiologic spinal motor output contributing to distinctive features of spasticity. However, the previous TSS studies used almost identical protocols in terms of stimulation frequency and intensity despite the great flexibility offered by this treatment strategy and the favorable results with the epidural stimulation at higher frequencies. Therefore, the proposed study takes a new direction to systematically investigate the standalone and comparative efficacy of four TSS interventions, including those used in previous studies. Our central hypothesis is that electrical neuromodulation with the selected TSS protocols (frequency: 50/100 Hz; intensity: 0.45 or 0.9 times the sub-motor threshold) can reduce and distinctly modify tonic and phasic components of spasticity on short- and long-term basis. We will test our hypothesis using a prospective, experimental, cross-over, assessor-masked study design in 12 individuals with chronic SCI (more than 1-year post-injury). Aim 1. Determine the time course of changes and immediate after-effects of each TSS protocol on tonic and phasic spasticity. The results will reveal the evolution of changes in spasticity during 30-min of TSS and the most effective protocol for producing immediate aftereffects. Aim 2. Determine the effect of TSS on spasticity after a trial of home-based therapy with each protocol. The participants will administer 30 min of TSS daily for six days with each of the four TSS protocols selected randomly. This aim will reveal the long-term carry-over effects of TSS intervention on various components of spasticity after SCI. Aim 3. Determine the participants' experience with TSS as a home-based therapy through focus group meetings. We will conduct focus group meetings after participants finish the home-based therapy trial. Accomplishing this specific aim will provide a valuable perspective on the value, challenges, and acceptability of TSS as a home-based intervention. The study addresses important questions for advancing scientific knowledge and clinical management of spasticity after SCI. Specifically, it will examine the efficacy of TSS frequencies and intensities on tonic and phasic spasticity. The study results will be relevant for a high proportion of individuals living with SCI that could benefit from this novel and low-cost non-pharmacological approach to managing spasticity after SCI.

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 data supports the effectiveness of the treatment Electrical Neuromodulation, Transcutaneous Spinal Stimulation (TSS) for spasticity?

Research shows that transcutaneous spinal cord stimulation (TSS) can temporarily reduce spasticity (muscle stiffness) in people with spinal cord injuries. Studies found that TSS improved muscle control and reduced spasms, suggesting it could be a helpful non-drug option for managing spasticity. ^{1 2 3 4 5}

Is electrical neuromodulation safe for humans?

Research on electrical neuromodulation, including transcutaneous spinal stimulation (TSS), shows it is generally safe for humans. Studies have reported improvements in spasticity and other functions without significant adverse effects, suggesting it is a safe non-invasive treatment option. ^{2 6 7 8 9}

How does the treatment Electrical Neuromodulation differ from other treatments for spasticity?

Electrical Neuromodulation, specifically Transcutaneous Spinal Stimulation (TSS), is unique because it is a non-invasive treatment that uses electrical currents to stimulate the spinal cord, potentially reducing spasticity and improving motor function. Unlike traditional drug therapies, it directly targets the nervous system to modulate muscle activity and enhance voluntary movement. ^{1 3 4 6 10}

Research Team

Matthias J Krenn, PhD

Principal Investigator

University of Mississippi Medical Center

Eligibility Criteria

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

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

Treatment Details

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.

Participant Groups

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+

Findings from Research

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]

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]

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]

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 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]

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]

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]

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]

References

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

Electrical stimulation in treating spasticity resulting from spinal cord injury. [2006]

2. England 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. [2022]

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

Transcutaneous Spinal Cord Stimulation and Motor Rehabilitation in Spinal Cord Injury: A Systematic Review. [2021]

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

Optimizing sensory fiber activation during cervical transcutaneous spinal stimulation using different electrode configurations: A computational analysis. [2022]

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

Transcutaneous Spinal Cord Stimulation Induces Temporary Attenuation of Spasticity in Individuals with Spinal Cord Injury. [2021]

6. England pubmed.ncbi.nlm.nih.gov

Treatment of spinal spasticity by electrical stimulation. [2019]

7. England pubmed.ncbi.nlm.nih.gov

Effects of transcutaneous spinal stimulation on spatiotemporal cortical activation patterns: a proof-of-concept EEG study. [2022]

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

Transcutaneous spinal cord stimulation and motor responses in individuals with spinal cord injury: A methodological review. [2022]

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

Efficacy of Transcutaneous Spinal Stimulation versus Whole Body Vibration for Spasticity Reduction in Persons with Spinal Cord Injury. [2021]

10. Spain pubmed.ncbi.nlm.nih.gov

Transcutaneous electrical nerve stimulation for spasticity: A systematic review. [2021]