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

Trial Summary

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 data supports the effectiveness of the treatment Transcutaneous Spinal Stimulation for muscle stiffness after spinal cord injury?

Research shows that Transcutaneous Spinal Stimulation (TSS) can activate muscles and improve motor function in people with spinal cord injuries. Studies have found that TSS can increase muscle strength and voluntary movement, making it a promising non-invasive treatment for improving motor recovery. ^{1 2 3 4 5}

Is transcutaneous spinal stimulation (TSS) safe for humans?

Transcutaneous spinal stimulation (TSS) is generally considered safe, but it can cause discomfort at high levels of stimulation. Studies have explored ways to reduce this discomfort, but no method has been found to be significantly better than the standard approach. ^{2 6 7 8 9}

How is Transcutaneous Spinal Stimulation different from other treatments for muscle stiffness after spinal cord injury?

Transcutaneous Spinal Stimulation (TSS) is unique because it is a non-invasive treatment that uses electrical stimulation to activate spinal circuits and enhance motor function, unlike other treatments that may not directly target the spinal cord's sensorimotor networks. It can increase motoneuron output and promote motor recovery by stimulating the spinal cord through the skin, offering a promising approach for improving voluntary movement and muscle strength in individuals with spinal cord injury. ^{2 3 5 10 11}

What is the purpose of this trial?

People with spinal cord injuries may experience muscle tightness or uncontrollable spasms. This study is being conducted to investigate whether transcutaneous spinal stimulation can improve these symptoms. Transcutaneous spinal stimulation is a non-surgical intervention by applying electrical currents using skin electrodes over the lower back and belly. The investigators want to see how well the intervention of transcutaneous spinal stimulation performs by testing different levels of stimulation pulse rates. Also, transcutaneous spinal stimulation is compared to muscle relaxants such as baclofen and tizanidine, commonly given to people with spinal cord injuries, to reduce muscle stiffness and spasms. By doing this, the investigators hope to discover if transcutaneous spinal stimulation similarly reduces muscle spasms and stiffness or if combining both methods works best. This could help improve treatment options for people with spinal cord injuries in the future.

Research Team

Matthias J Krenn, Ph.D.

Principal Investigator

University of Mississippi Medical Center

Eligibility Criteria

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

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

Treatment Details

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.

Participant Groups

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+

Findings from Research

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]

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]

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]

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]

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]

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]

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]

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]

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]

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]

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]

References

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

Characterization of interlimb interaction via transcutaneous spinal stimulation of cervical and lumbar spinal enlargements. [2023]

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

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

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

Transspinal stimulation increases motoneuron output of multiple segments in human spinal cord injury. [2023]

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. Switzerland pubmed.ncbi.nlm.nih.gov

Voluntary Modulation of Evoked Responses Generated by Epidural and Transcutaneous Spinal Stimulation in Humans with Spinal Cord Injury. [2022]

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

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

7. United States 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. [2021]

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

Optimization of Transspinal Stimulation Applications for Motor Recovery after Spinal Cord Injury: Scoping Review. [2023]

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

Transcutaneous spinal stimulation provides characterization of neurological status in individuals with tetraplegia. [2023]

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

Common neural structures activated by epidural and transcutaneous lumbar spinal cord stimulation: Elicitation of posterior root-muscle reflexes. [2019]

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

Noninvasive Reactivation of Motor Descending Control after Paralysis. [2018]