SCAP and Hand Exercises for ALS

Overseen By Noam Y Harel, MD PhD

Age: 18+

Sex: Any

Travel: May Be Covered

Time Reimbursement: Varies

Trial Phase: Academic

Recruiting

Sponsor: VA Office of Research and Development

Must not be taking: Amphetamines, Dalfampridine

Disqualifiers: Seizures, Ventilator dependence, Cardiac disease, others

No Placebo Group

Trial Summary

What is the purpose of this trial?

Veterans are at higher risk than non-Veterans of falling ill with amyotrophic lateral sclerosis (ALS). The investigators have shown that synchronized stimulation over the brain and cervical spinal cord can temporarily strengthen weakened nerve circuits between the brain and hand muscles in people with ALS. The current proposal will take the next step of individualizing this intervention, then applying it repetitively in an attempt to achieve direct clinical benefit on hand strength and function. Following an initial 2-3 month period of optimizing the intervention for each individual, the investigators will compare the effects of two-week programs of paired brain-spinal stimulation with or without hand exercises.

Will I have to stop taking my current medications?

The trial does not specify if you need to stop taking your current medications, but you cannot participate if you use medications that significantly lower the seizure threshold, like amphetamines and dalfampridine.

What data supports the effectiveness of the treatment SCAP and Hand Exercises for ALS?

Research shows that combining spinal cord transcutaneous stimulation with activity-based training can improve upper limb function in people with spinal cord injuries. This suggests that similar approaches might help in conditions like ALS, where improving hand and arm function is important. ^{1 2 3 4 5}

Is cervical spinal cord stimulation safe for humans?

Research on cervical spinal cord stimulation, including studies on people with spinal cord injuries and post-stroke conditions, suggests it is generally safe, with no serious adverse events reported in the studies reviewed. ^{2 4 6 7 8}

How does the SCAP and Hand Exercises treatment for ALS differ from other treatments?

The SCAP and Hand Exercises treatment is unique because it combines non-invasive spinal cord stimulation with task-oriented hand exercises to enhance neuroplasticity (the brain's ability to reorganize itself) and improve upper limb function. This approach is different from traditional therapies as it specifically targets spinal circuits to facilitate recovery, which has shown promising results in improving motor function in conditions like spinal cord injury. ^{1 2 4 8 9}

Research Team

Noam Y Harel, MD PhD

Principal Investigator

James J. Peters Veterans Affairs Medical Center

Eligibility Criteria

This trial is for Veterans with ALS, a motor neuron disease. It's more inclusive than most studies, giving many Veterans the chance to join in research for this service-connected condition. Specific eligibility details are not provided but generally include those affected by ALS.

Inclusion Criteria

I have been diagnosed with ALS according to specific medical criteria.

My muscle response to a nerve stimulation test is strong and within normal limits.

I have some weakness in my hand movements.

Exclusion Criteria

I am not taking medications like amphetamines that increase my risk of seizures.

I have had a severe head injury with brain damage or skull fracture.

I have a history of severe ringing in my ears.

Trial Timeline

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Optimization

SCAP synaptic pairing interval and repetitive frequency pattern will be individually optimized to enhance hand muscle excitability and dexterity.

2-3 months

Consolidation

Two-week programs of SCAP alone versus SCAP plus task-oriented hand exercise will be compared.

2 weeks

6 sessions

Follow-up

Participants are monitored for safety and effectiveness after treatment

up to 6 months

Treatment Details

Interventions

• Spinal Cord Associative Plasticity (SCAP) (Procedure)
• Upper extremity task-oriented exercise (Procedure)

Trial Overview The study tests whether customized brain-spinal stimulation combined with hand exercises can improve hand strength and function in ALS patients compared to either treatment alone. Participants will undergo two-week programs of these interventions.

Participant Groups

Group I: SCAP plus task-oriented exercise Experimental Treatment 2 Interventions

After a run-in phase of 2-4 months to determine individualized stimulation parameters, participants will be randomized into a comparator group of two weeks (6 sessions) of SCAP intervention plus upper extremity task-oriented exercise.

Group II: SCAP alone Active Control 1 Intervention

After a run-in phase of 2-4 months to determine individualized stimulation parameters, participants will be randomized into a comparator group of two weeks (6 sessions) of SCAP intervention alone.

Who Is Running the Clinical Trial?

VA Office of Research and Development

Lead Sponsor

Trials

1,691

Recruited

3,759,000+

Findings from Research

A multicenter randomized clinical trial is investigating the effectiveness of combining spinal cord transcutaneous stimulation (scTS) with activity-based training (ABT) for improving upper extremity function in individuals with cervical spinal cord injury, showing promising preliminary results.

In a small sample of four participants, the combination of scTS and ABT led to immediate and sustained improvements in upper extremity function, with one participant experiencing a remarkable 5-fold increase in function, indicating potential for significant rehabilitation benefits.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Combining Spinal Cord Transcutaneous Stimulation with Activity-based Training to Improve Upper Extremity Function Following Cervical Spinal Cord Injury. Zhang, F., Carnahan, J., Ravi, M., et al.[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]

Transcutaneous spinal stimulation (TSS) can selectively activate different upper-limb muscle groups in individuals with spinal cord injuries, depending on the placement of electrodes along the cervical spine.

This targeted approach may enhance the effectiveness of TSS in restoring a wider range of motor functions after neurological injuries, suggesting a promising avenue for rehabilitation in severe spinal cord injury cases.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Cervical transcutaneous spinal stimulation for spinal motor mapping. Oh, J., Steele, AG., Varghese, B., et al.[2022]

Cervical transcutaneous spinal cord stimulation (tSCS) effectively activates hand muscles more when the cathode is placed over the T1 vertebra compared to C6 and C7, indicating that electrode placement is crucial for optimizing muscle activation.

Higher stimulation intensities are needed to activate distal hand muscles compared to proximal arm muscles, suggesting different excitability thresholds, which is important for tailoring rehabilitation strategies.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Selectivity and excitability of upper-limb muscle activation during cervical transcutaneous spinal cord stimulation in humans. de Freitas, RM., Sasaki, A., Sayenko, DG., et al.[2021]

Pairing Transcranial Magnetic Stimulation (TMS) with transcutaneous Spinal Cord Stimulation (tSCS) significantly increases corticospinal excitability and motor performance in healthy subjects, particularly when the stimulation is timed to arrive simultaneously at the spinal motoneurons.

The study found that tSCS produced a greater facilitation of motor evoked potentials compared to Peripheral Nerve Stimulation (PNS), suggesting that tSCS may be more effective for enhancing neuroplastic recovery in individuals with spinal cord injury.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

The Immediate and Short-Term Effects of Transcutaneous Spinal Cord Stimulation and Peripheral Nerve Stimulation on Corticospinal Excitability. Al'joboori, Y., Hannah, R., Lenham, F., et al.[2021]

Cervical transcutaneous spinal cord stimulation (tSCS) effectively activates sensory pathways that converge on motor pools for upper limb muscles, indicating its potential for enhancing motor function.

The study provides novel evidence of how cervical tSCS engages the sensory afferent system, demonstrating its utility for both electrophysiological assessments and neurorehabilitation in improving upper limb sensorimotor function.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

On the reflex mechanisms of cervical transcutaneous spinal cord stimulation in human subjects. Milosevic, M., Masugi, Y., Sasaki, A., et al.[2020]

In a first-in-human study involving two participants with chronic post-stroke hemiparesis, electrical stimulation of cervical spinal circuits significantly improved arm and hand motor control, with increases in grip strength (up to +108%) and movement speed (up to +40%).

Both participants experienced lasting improvements in motor function even after stimulation was stopped, and no serious adverse events were reported, suggesting that spinal cord stimulation may be a safe and effective method for aiding upper-limb recovery after a stroke.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Epidural stimulation of the cervical spinal cord for post-stroke upper-limb paresis. Powell, MP., Verma, N., Sorensen, E., et al.[2023]

Transcutaneous electrical spinal cord stimulation combined with physical therapy led to significant improvements in upper extremity function for a 62-year-old male with a chronic incomplete spinal cord injury, including a 52-point increase in strength and sensation scores after four weeks of treatment.

Remarkably, the functional gains achieved persisted for over three months after the treatment ended, indicating that this noninvasive approach can promote lasting neuroplasticity and recovery in individuals with spinal cord injuries.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Transcutaneous Electrical Spinal Stimulation Promotes Long-Term Recovery of Upper Extremity Function in Chronic Tetraplegia. Inanici, F., Samejima, S., Gad, P., et al.[2020]

Combining electrical enabling motor control (eEmc) with hand grip training significantly improves hand function in healthy individuals more than either method alone, suggesting enhanced motor output and plastic changes in the nervous system.

The study involved 10 participants and demonstrated that this combination therapy not only increased hand grip strength but also induced beneficial changes in spinal and cortical activity, indicating a more adaptable state for motor control.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Cervical Electrical Neuromodulation Effectively Enhances Hand Motor Output in Healthy Subjects by Engaging a Use-Dependent Intervention. Kumru, H., Flores, Á., Rodríguez-Cañón, M., et al.[2022]

References

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

Combining Spinal Cord Transcutaneous Stimulation with Activity-based Training to Improve Upper Extremity Function Following Cervical Spinal Cord Injury. [2023]

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

Cervical transcutaneous spinal stimulation for spinal motor mapping. [2022]

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

Selectivity and excitability of upper-limb muscle activation during cervical transcutaneous spinal cord stimulation in humans. [2021]

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

The Immediate and Short-Term Effects of Transcutaneous Spinal Cord Stimulation and Peripheral Nerve Stimulation on Corticospinal Excitability. [2021]

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

On the reflex mechanisms of cervical transcutaneous spinal cord stimulation in human subjects. [2020]

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

Epidural stimulation of the cervical spinal cord for post-stroke upper-limb paresis. [2023]

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

Transcutaneous Electrical Spinal Stimulation Promotes Long-Term Recovery of Upper Extremity Function in Chronic Tetraplegia. [2020]

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

Cervical Electrical Neuromodulation Effectively Enhances Hand Motor Output in Healthy Subjects by Engaging a Use-Dependent Intervention. [2022]