Electrical Stimulation + Therapy for Multiple Sclerosis

Overseen By Fatma Inanici, MD, PhD

Age: 18+

Sex: Any

Trial Phase: Phase 1

Sponsor: University of Washington

Must not be taking: Botox, Dalfampridine

Disqualifiers: Neurological conditions, Psychiatric illness, Serious comorbidities, 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: 6

4 Participants Needed

Trial Summary

What is the purpose of this trial?

Current disease-modifying therapies for multiple sclerosis (MS) aim to prevent the development of new lesions; unfortunately, no current FDA-approved therapies promote central nervous system (CNS) repair mechanisms. Thus, strategies to promote functional recovery from lesion-related deficits in adults with MS remain an unmet need. This is a pilot study designed to test the feasibility, safety and preliminary efficacy of non-invasive (transcutaneous, applied by surface electrodes over the skin) electrical spinal cord stimulation combined with occupational therapy for restoring upper extremity sensorimotor function in adults with multiple sclerosis. Participants with multiple sclerosis and impaired upper extremity function will complete two separate 6-week intervention sessions: 6 weeks of occupational therapy combined with transcutaneous spinal cord stimulation and 6 weeks of occupational therapy alone. The order of these interventions will be randomized, and each intervention will be separated by a 6-week washout period. The investigators hypothesize that: 1. transcutaneous spinal cord stimulation combined with therapy will be feasible and acceptable by participants 2. transcutaneous spinal cord stimulation combined with therapy will lead to improvements in upper extremity function compared to occupational therapy alone 3. transcutaneous spinal cord stimulation combined with therapy will lead to improvements in symptoms related to quality of life (pain, spasticity, and bladder symptoms) compared to occupational therapy alone

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 does mention that you cannot participate if you have unstable dalfampridine usage during the study. It's best to discuss your current medications with the study team to see if they might affect your eligibility.

What data supports the effectiveness of this treatment for multiple sclerosis?

Research shows that electrical spinal cord stimulation can improve bladder symptoms in multiple sclerosis patients and may also help with other symptoms. Additionally, similar treatments have been shown to aid recovery in spinal cord injuries by promoting nerve cell growth and improving motor function. ^{1 2 3 4 5}

Is electrical spinal cord stimulation safe for humans?

Electrical spinal cord stimulation has been used for various conditions, and while it is generally considered safe, there are potential risks like spinal cord injury during implantation. Transcutaneous electrical stimulation, a non-invasive form, has shown safety in multiple sclerosis patients with bladder symptoms and walking disabilities. ^{1 6 7 8 9}

How is the treatment of non-invasive electrical spinal cord stimulation for multiple sclerosis different from other treatments?

Non-invasive electrical spinal cord stimulation is unique because it uses electrical currents applied through the skin to stimulate the spinal cord, potentially improving symptoms like bladder issues and walking difficulties in multiple sclerosis patients. This method is non-invasive, meaning it doesn't require surgery, and it may activate neural stem cells in the spinal cord, promoting recovery and regeneration. ^{1 2 4 5 10}

Research Team

Sarah Simmons, MD, PhD

Principal Investigator

University of Washington

Eligibility Criteria

This trial is for adults with multiple sclerosis who have trouble with hand and arm functions. Participants will undergo two 6-week sessions of therapy, one combined with non-invasive spinal cord stimulation and one with just occupational therapy.

Inclusion Criteria

For women of childbearing potential, willingness to provide confirmation of a negative over-the-counter home pregnancy test within 2 weeks of study entry and prior to each intervention arm

I have been diagnosed with multiple sclerosis (MS).

Presence of upper extremity functional impairment (correlating with raw score ≤34 on NeuroQOL Upper Extremity Function short-form questionnaire)

Exclusion Criteria

My condition has worsened in the last 6 months.

Active implanted stimulator or baclofen pump

Serious comorbidities that would prevent participation in study activities

Timeline

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment: Hand Therapy + Stimulation

Participants receive non-invasive transcutaneous electrical spinal cord stimulation paired with hand therapy sessions

6 weeks

3 visits per week (in-person)

Washout

A 6-week period with no intervention to allow for the effects of the first treatment to dissipate

6 weeks

Treatment: Hand Therapy alone

Participants undergo hand therapy sessions without spinal cord stimulation

6 weeks

3 visits per week (in-person)

Follow-up

Participants are monitored for safety and effectiveness after treatment

4 weeks

Treatment Details

Interventions

• Non-invasive Electrical Spinal Cord Stimulation

Trial Overview The study tests if adding electrical spinal cord stimulation to regular occupational therapy can better improve hand and arm function in MS patients than therapy alone. It's a pilot study, meaning it's an early test to see if the idea works well enough for more research.

Participant Groups

Group I: Hand Therapy + Stimulation Experimental Treatment 2 Interventions

Participants will receive non-invasive transcutaneous electrical spinal cord stimulation paired with hand therapy sessions three times per week, 60 minutes per session, for six weeks.

Group II: Hand Therapy alone Active Control 1 Intervention

Participants randomized to hand therapy alone will participate in therapy sessions three times per week, 60 minutes per session for six weeks.

Non-invasive Electrical Spinal Cord Stimulation is already approved in United States, European Union for the following indications:

Approved in United States as Transcutaneous Spinal Cord Stimulation for:

• Chronic pain
• Failed back surgery syndrome
• Complex regional pain syndrome
• Diabetic peripheral neuropathy

Approved in European Union as Transcutaneous Spinal Cord Stimulation for:

• Chronic pain
• Neuropathic pain
• Spinal cord injuries

Who Is Running the Clinical Trial?

University of Washington

Lead Sponsor

Trials

1,858

Recruited

2,023,000+

Findings from Research

In a study involving 49 multiple sclerosis patients, both electrical spinal cord stimulation and transcutaneous electrical stimulation led to significant subjective and objective improvements in bladder symptoms.

Transcutaneous electrical stimulation may serve as an effective preliminary treatment to identify patients who would benefit from subsequent electrical spinal cord stimulation.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Electrical stimulation in multiple sclerosis. Comparison of transcutaneous electrical stimulation and epidural spinal cord stimulation. Fredriksen, TA., Bergmann, S., Hesselberg, JP., et al.[2006]

In a pilot study involving 7 individuals with chronic spinal cord injury, the use of transcutaneous electrical spinal cord stimulation (TSCS) combined with functional training led to improvements in upper and lower extremity function, with all participants showing progress on the Capabilities of Upper Extremity Test (CUE-T).

Notably, two participants improved their ASIA impairment scale classification, and five individuals experienced enhanced sensation, demonstrating that TSCS can facilitate recovery even after a plateau in rehabilitation progress, without any serious adverse events.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Transcutaneous Electrical Spinal Cord Stimulation to Promote Recovery in Chronic Spinal Cord Injury. Tefertiller, C., Rozwod, M., VandeGriend, E., 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 direct current stimulation (tsDCS) has been shown to have dose-dependent effects on spinal and cortical excitability in healthy subjects, indicating its potential for modulating neural activity.

In a study involving nine healthy participants, both anodal and cathodal tsDCS demonstrated significant effects on motor evoked potentials and spinal cord excitability, suggesting that further research with larger samples could expand treatment options for spinal cord injury patients.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Dose-response relationship of transcutaneous spinal direct current stimulation in healthy humans: A proof of concept study. Powell, ES., Korupolu, R., Westgate, PM., et al.[2019]

Electrical stimulation significantly enhances the proliferation and differentiation of spinal cord-derived neural stem/progenitor cells (SC-NSPCs) in both in vitro and in vivo rodent models of spinal cord injury (SCI), leading to improved functional recovery.

The mechanism behind these benefits appears to involve the activation of the Wnt/β-catenin signaling pathway, suggesting that electrical stimulation could be a promising noninvasive treatment strategy for promoting neural regeneration after SCI.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Electrical stimulation promotes functional recovery after spinal cord injury by activating endogenous spinal cord-derived neural stem/progenitor cell: an in vitro and in vivo study. Bang, WS., Han, I., Mun, SA., et al.[2023]

In a study of 69 patients with implanted spinal cord stimulators (SCSs) who underwent 78 MRI scans, the overall adverse event rate for off-label MRI use was low at 9.72%, with no serious adverse events reported.

All reported clinical adverse events were minor and resolved, suggesting that the benefits of MRI for pain management in patients with older SCS models may outweigh the associated risks.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Off-Label Magnetic Resonance Imaging (MRI) in Patients with Persistent Pain with Spinal Cord Stimulators: A Case Series. Ragukonis, T.[2022]

Spinal cord stimulation (SCS) is generally a safe and effective treatment option, with complications being uncommon according to a comprehensive literature review.

The review emphasizes the importance of proper patient selection and adherence to evidence-based guidelines to minimize the risk of complications during SCS implantation.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Anticipating and preventing complications in spinal cord stimulator implantation. Falowski, SM., Tan, H., Parks, J., et al.[2023]

In a study of 8326 patients who underwent spinal cord stimulation (SCS) implantation, the overall incidence of spinal cord injury (SCI) was found to be low at 2.13%, indicating that SCS is a generally safe procedure.

There was no significant difference in the rates of SCI or spinal hematoma between patients receiving percutaneous (2.35%) and paddle (1.71%) electrode implantation, suggesting similar safety profiles for both methods.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

The Incidence of Spinal Cord Injury in Implantation of Percutaneous and Paddle Electrodes for Spinal Cord Stimulation. Petraglia, FW., Farber, SH., Gramer, R., et al.[2022]

In a clinical trial involving 83 patients with chronic back pain, 88% reported significant pain relief after using a high-frequency spinal cord stimulation (SCS) system, with back pain scores dropping from an average of 8.4 to 2.7 after six months.

The high-frequency SCS system not only provided substantial pain relief without causing the tingling sensation (paresthesia) typical of traditional SCS but also improved patients' disability and sleep quality, confirming its safety and efficacy.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

High-frequency spinal cord stimulation for the treatment of chronic back pain patients: results of a prospective multicenter European clinical study. Van Buyten, JP., Al-Kaisy, A., Smet, I., et al.[2022]

Electrical stimulation of the spinal cord has been explored as a treatment for multiple sclerosis, potentially offering new therapeutic options for managing symptoms.

The study discusses the physiological mechanisms behind how electrical fields can affect spinal cord function, which may lead to improved understanding and treatment strategies for multiple sclerosis.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Functional stimulation of the spinal cord in multiple sclerosis. Cook, AW., Taylor, JK., Nidzgorski, F.[2019]

References

1. Switzerland pubmed.ncbi.nlm.nih.gov

Electrical stimulation in multiple sclerosis. Comparison of transcutaneous electrical stimulation and epidural spinal cord stimulation. [2006]

2. Switzerland pubmed.ncbi.nlm.nih.gov

Transcutaneous Electrical Spinal Cord Stimulation to Promote Recovery in Chronic Spinal Cord Injury. [2022]

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

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

4. Netherlands pubmed.ncbi.nlm.nih.gov

Dose-response relationship of transcutaneous spinal direct current stimulation in healthy humans: A proof of concept study. [2019]

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

Electrical stimulation promotes functional recovery after spinal cord injury by activating endogenous spinal cord-derived neural stem/progenitor cell: an in vitro and in vivo study. [2023]

6. New Zealand pubmed.ncbi.nlm.nih.gov

Off-Label Magnetic Resonance Imaging (MRI) in Patients with Persistent Pain with Spinal Cord Stimulators: A Case Series. [2022]

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

Anticipating and preventing complications in spinal cord stimulator implantation. [2023]

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

The Incidence of Spinal Cord Injury in Implantation of Percutaneous and Paddle Electrodes for Spinal Cord Stimulation. [2022]

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

High-frequency spinal cord stimulation for the treatment of chronic back pain patients: results of a prospective multicenter European clinical study. [2022]

10. England pubmed.ncbi.nlm.nih.gov

Functional stimulation of the spinal cord in multiple sclerosis. [2019]