Spinal Cord Stimulation for Stiff Person Syndrome

Overseen By Janus S Patel, MD

Age: 18+

Sex: Any

Trial Phase: Academic

Sponsor: Wake Forest University Health Sciences

Must not be taking: Opioids, Anticoagulants

Disqualifiers: Spine surgery, Severe stenosis, others

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

Approved in 3 Jurisdictions This treatment is already approved in other countries

Compensation: Varies

Number of Visits: 2

Duration: 10 days

10 Participants Needed

Trial Summary

Will I have to stop taking my current medications?

The trial requires that if you are taking oral medications, you must maintain a stable regimen (no changes in dosage or frequency) for the duration of the study.

What data supports the effectiveness of the treatment Spinal Cord Stimulation for Stiff Person Syndrome?

Research shows that transcutaneous spinal cord stimulation (tSCS), a part of the treatment, can enhance muscle activation and improve motor function in people with spinal cord injuries. This suggests it might help with muscle control and movement in conditions like Stiff Person Syndrome. ^{1 2 3 4 5}

Is spinal cord stimulation generally safe for humans?

Spinal cord stimulation, including transcutaneous and epidural methods, is generally considered safe for humans. It has been used in various conditions like spinal cord injury, chronic pain, and diabetic neuropathy, with studies indicating it can improve motor function and reduce pain. However, specific risks and complications can vary, and more research is needed to fully understand these aspects. ^{1 4 6 7 8}

How does spinal cord stimulation differ from other treatments for Stiff Person Syndrome?

Spinal cord stimulation, particularly transcutaneous spinal cord stimulation (tSCS), is unique because it is a non-invasive treatment that uses electrical currents to stimulate the spinal cord and activate motor responses. Unlike other treatments, it does not require surgery or medication and can enhance voluntary movement and muscle strength by targeting specific spinal segments. ^{1 2 3 4 9}

What is the purpose of this trial?

The purpose of this prospective pilot study is to gather preliminary evidence evaluating spinal cord stimulation (SCS) as a potential therapy for the treatment of rigidity and painful spasms in patients with stiff person syndrome (SPS), a rare autoimmune neurological condition. The hypothesis is that SCS-mediated clinical improvement occurs through multi-modal mechanisms of action targeting several components of neuronal inhibitory signaling pathways in the spinal cord.

Research Team

Janus S Patel, MD

Principal Investigator

Wake Forest University Health Sciences

Eligibility Criteria

This trial is for adults diagnosed with stiff person syndrome (SPS) who have tried at least two conventional therapies without enough relief or experienced intolerable side effects. Participants must have anti-GAD65 antibodies, maintain a stable oral medication regimen during the study, and be cleared for an implantable device. Exclusions include recent immunoglobulin therapy, bleeding disorders, opioid misuse, active infections or malignancy, certain mental health conditions, pregnancy, litigation related to chronic pain claims.

Inclusion Criteria

I am willing and able to sign a consent form.

Is cleared for an implantable medical device by licensed mental health provider

I have been diagnosed with stiff person syndrome.

Exclusion Criteria

I have a blood clotting issue or low platelets, or I can't stop my blood thinner for a test.

I had a spine infection in the last 6 months.

I do not have an infection or active cancer at the surgery site.

Timeline

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Placement of spinal cord stimulator trial leads and evaluation of its effects on rigidity and painful spasms

10 days

1 visit (in-person) for lead placement, multiple assessments up to day 10

Follow-up

Participants are monitored for safety and effectiveness after treatment, including pain level reassessment at 14 days after trial leads removed

14 days

1 visit (in-person) for follow-up assessment

Treatment Details

Interventions

• Spinal Cord Stimulation

Trial Overview The trial is testing spinal cord stimulation (SCS) as a treatment for rigidity and spasms in SPS patients. It's a prospective pilot study designed to see if SCS can improve symptoms by affecting neuronal inhibitory signaling pathways in the spinal cord.

Participant Groups

Group I: SCS trial lead Experimental Treatment 1 Intervention

placement of spinal cord stimulator trial leads

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

Approved in United States as Spinal Cord Stimulation for:

• Failed back surgery syndrome (FBSS)
• Adhesive arachnoiditis
• Peripheral causalgia/neuropathy
• Reflex sympathetic dystrophy (RSD)
• Phantom limb/stump pain
• Ischemic pain of vascular origin
• Complex regional pain syndrome
• Pain after an amputation
• Visceral abdominal pain and perineal pain

Approved in European Union as Spinal Cord Stimulation for:

• Chronic pain
• Neuropathic pain
• Spinal cord injury pain
• Failed back surgery syndrome (FBSS)
• Adhesive arachnoiditis
• Peripheral causalgia/neuropathy
• Reflex sympathetic dystrophy (RSD)

Approved in Canada as Spinal Cord Stimulation for:

• Chronic pain
• Neuropathic pain
• Spinal cord injury pain
• Failed back surgery syndrome (FBSS)
• Adhesive arachnoiditis
• Peripheral causalgia/neuropathy
• Reflex sympathetic dystrophy (RSD)

Who Is Running the Clinical Trial?

Wake Forest University Health Sciences

Lead Sponsor

Trials

1,432

Recruited

2,506,000+

Findings from Research

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 electrical spinal cord stimulation (tSCS) can induce involuntary locomotor-like stepping movements in non-injured humans, suggesting its potential for rehabilitation.

Increasing the frequency of tSCS from 5 to 30 Hz enhances the amplitude of these stepping movements, indicating that tSCS effectively activates locomotor circuitry through the dorsal roots.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

[Transcutaneous electrical stimulation of the spinal cord: non-invasive tool for activation of locomotor circuitry in human]. Gorodnichev, RM., Pivovarova, EA., Pukhov, A., et al.[2012]

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 involving 15 healthy participants, transcutaneous electrical spinal cord stimulation (tSCS) significantly increased quadriceps motor evoked potentials (Q-MEP) during active stimulation compared to baseline and sham stimulation, indicating its potential for enhancing motor function.

The study found no significant changes in tibialis anterior motor evoked potentials (TA-MEP) or isometric strength, suggesting that tSCS specifically targets certain muscle responses, potentially reflecting its mechanism of action at the interneuronal or motoneuronal level.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Transcutaneous Spinal Cord Stimulation Enhances Quadriceps Motor Evoked Potential in Healthy Participants: A Double-Blind Randomized Controlled Study. Megía-García, Á., Serrano-Muñoz, D., Taylor, J., et al.[2020]

In a study of 68 patients who had spinal cord stimulation paddle electrodes removed, the most common reason for removal was loss of coverage or effect (75%), indicating that while SCS is effective, it may not always provide lasting relief.

Postoperative complications occurred in 11.75% of patients, with two major complications requiring reoperation, highlighting that while SCS removal is generally safe, it does carry some risks that patients should be aware of.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Rate of Complications Following Spinal Cord Stimulation Paddle Electrode Removal. Maldonado-Naranjo, AL., Frizon, LA., Sabharwal, NC., et al.[2022]

Epidural spinal electrostimulation (ESES) has shown promising results in improving spinal spasticity and mobility by 20 to 30% in patients with multiple sclerosis and myelopathy, indicating its efficacy in treating severe central motor disturbances.

In addition to mobility improvements, ESES led to a complete disappearance of spastic cramps in all treated cases and significant pain relief in three patients with chronic pain, suggesting its potential as a non-surgical intervention for chronic pain management.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

[Epidural spinal electrostimulation (ESES) in patients with chronic pain and central motor disturbances (author's transl)]. Klingler, D., Kepplinger, B., Gerstenbrand, F., et al.[2006]

Electrical spinal cord stimulation (ESCS) provides significant and sustained pain relief for patients with chronic painful diabetic neuropathy, with median pain scores showing a marked reduction when the stimulator is on compared to when it is off.

The procedure has a low complication rate, with only two late complications reported among the patients, indicating that ESCS is a safe long-term treatment option for managing chronic pain.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Electrical spinal cord stimulation in the long-term treatment of chronic painful diabetic neuropathy. Daousi, C., Benbow, SJ., MacFarlane, IA.[2019]

In a double-blinded study involving 2 male patients with incomplete spinal cord injury, anodal transcutaneous spinal direct current stimulation (tsDCS) improved all measured outcomes, including gait and balance, while cathodal tsDCS showed mixed results.

Both types of tsDCS were able to modulate corticospinal excitability, indicating that this non-invasive method could be a promising approach for enhancing rehabilitation in patients with spinal cord injuries.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Spinal direct current stimulation with locomotor training in chronic spinal cord injury. Abualait, TS., Ibrahim, AI.[2021]

References

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

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

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

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

3. Russia (Federation) pubmed.ncbi.nlm.nih.gov

[Transcutaneous electrical stimulation of the spinal cord: non-invasive tool for activation of locomotor circuitry in human]. [2012]

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

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

5. Switzerland pubmed.ncbi.nlm.nih.gov

Transcutaneous Spinal Cord Stimulation Enhances Quadriceps Motor Evoked Potential in Healthy Participants: A Double-Blind Randomized Controlled Study. [2020]

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

Rate of Complications Following Spinal Cord Stimulation Paddle Electrode Removal. [2022]

7. Austria pubmed.ncbi.nlm.nih.gov

[Epidural spinal electrostimulation (ESES) in patients with chronic pain and central motor disturbances (author's transl)]. [2006]

8. England pubmed.ncbi.nlm.nih.gov

Electrical spinal cord stimulation in the long-term treatment of chronic painful diabetic neuropathy. [2019]

9. Saudi Arabia pubmed.ncbi.nlm.nih.gov

Spinal direct current stimulation with locomotor training in chronic spinal cord injury. [2021]