Spinal Cord Stimulation for Spinal Muscular Atrophy

Overseen by Marco Capogrosso

Age: Any Age

Sex: Any

Travel: May Be Covered

Time Reimbursement: Varies

Trial Phase: Academic

Recruiting

Sponsor: Marco Capogrosso

Must be taking: SMN inducing therapies

Must not be taking: Anticoagulants, Anti-spasticity, Anti-seizure

Disqualifiers: Spinal deformation, Joint contractures, others

No Placebo Group

Approved in 3 Jurisdictions

Trial Summary

What is the purpose of this trial?

Spinal cord stimulation (SCS) has shown remarkable efficacy in restoring motor function in people with spinal cord injury by recruiting afferent input to enhance the responsiveness of spared neural circuits to residual cortical inputs. This pilot will test if SCS can show evidence to improve motor deficits in people with Type 2, 3, or 4 spinal muscular atrophy (SMA). The investigators will enroll up to six subjects with Type 2, 3, or 4 SMA aged 16 or older that show quantifiable motor deficits of the upper body. The investigators will then implant the subjects with percutaneous, linear spinal leads near the cervical spinal cord for a period of up to 29 days. Although these leads are not optimized for motor function but rather for their clinically approved indication of treating pain, the investigators believe they provide a safe technology enabling our team to perform scientific measurement necessary to evaluate potential for effects of SCS in motor paralysis with SMA. After the end of the study, the leads will be explanted.

Will I have to stop taking my current medications?

If you are taking anticoagulant, anti-spasticity, or anti-seizure medications, you will need to stop them at least 4 weeks before the lead implantation and cannot take them during the treatment phase of the study.

What data supports the effectiveness of the treatment Spinal Cord Stimulation for Spinal Muscular Atrophy?

Research on transcutaneous spinal cord stimulation (tSCS) shows it can enhance voluntary movement, muscle strength, and function in people with spinal cord injuries, suggesting potential benefits for similar conditions like Spinal Muscular Atrophy. ^{1 2 3 4 5}

Is spinal cord stimulation generally safe for humans?

Spinal cord stimulation, including transcutaneous spinal cord stimulation (tSCS), has been studied in various conditions and is generally considered safe, with studies showing it can enhance muscle activity and motor function without significant adverse effects. ^{2 4 5 6 7}

How does spinal cord stimulation treatment differ from other treatments for spinal muscular atrophy?

Spinal cord stimulation, including transcutaneous spinal cord stimulation (tSCS), is unique because it is a non-invasive treatment that uses electrical currents to stimulate spinal circuits, potentially enhancing muscle activation and motor function. Unlike other treatments, it directly targets the spinal cord to improve voluntary movement and muscle strength, which is particularly novel for conditions like spinal muscular atrophy where standard treatments may not exist. ^{1 2 3 4 6}

Research Team

Marco Capogrosso

Principal Investigator

University of Pittsburgh

Eligibility Criteria

This trial is for individuals aged 16 or older with Type 2, 3, or 4 Spinal Muscular Atrophy (SMA) who have motor deficits in the upper body. Participants will have a spinal cord stimulator implanted temporarily to test if it improves their motor functions.

Inclusion Criteria

I am between 18 and 64 years old.

I started my SMA treatment with Spinraza or risdiplam over 6 months ago.

I have been diagnosed with 5q-autosomal recessive SMA.

Exclusion Criteria

I do not have severe behavioral or cognitive issues that prevent me from participating.

SMA Participant: Subject has severe behavioral or cognitive problems that preclude participation in the study

I have severe joint stiffness that limits my movement for study tasks.

Trial Timeline

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants receive spinal cord stimulation with percutaneous spinal cord stimulation leads implanted in the cervical epidural space for up to 29 days

4 weeks

Regular visits for monitoring and adjustments

Follow-up

Participants are monitored for safety and effectiveness after treatment, including explantation of the leads

4 weeks

Treatment Details

Interventions

• Spinal Cord Stimulation (Procedure)

Trial Overview The study tests whether a Spinal Cord Stimulator can help improve upper limb motor function in people with SMA Types 2, 3, or 4. Up to six subjects will receive an implant near the cervical spinal cord for up to 29 days.

Participant Groups

Group I: Spinal Cord Stimulation Experimental Treatment 1 Intervention

All patients will receive FDA-approved percutaneous spinal cord stimulation leads implanted in the cervical epidural (C4-T1 vertebra) space. The leads will be connected to external stimulators (either FDA-approved or human-grade research stimulator with safety features) during research activities.

Spinal Cord Stimulation is already approved in Canada for the following indications:

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?

Marco Capogrosso

Lead Sponsor

Trials

3

Recruited

40+

Roche-Genentech

Industry Sponsor

Trials

27

Recruited

3,800+

Findings from Research

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]

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]

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]

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 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]

References

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

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

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

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

3. Switzerland pubmed.ncbi.nlm.nih.gov

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

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. England pubmed.ncbi.nlm.nih.gov

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

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

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

7. 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]