SCAP and Hand Exercises for ALS

Recruiting at 1 trial location

Overseen By Noam Y Harel, MD PhD

Age: 18+

Sex: Any

Trial Phase: Academic

Sponsor: VA Office of Research and Development

Must not be taking: Amphetamines, Dalfampridine

Disqualifiers: Seizures, Ventilator dependence, Cardiac disease, others

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

Compensation: Varies

Number of Visits: 6

32 Participants Needed

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial explores new methods to enhance hand strength and function in individuals with amyotrophic lateral sclerosis (ALS), a disease affecting nerve cells in the brain and spinal cord. Researchers are testing spinal cord associative plasticity (SCAP), a technique that stimulates nerve pathways, and examining its impact when combined with specific hand exercises. Participants will undergo a personalized adjustment period before being assigned to receive either the SCAP treatment alone or a combination of SCAP and hand exercises for two weeks. This trial suits individuals diagnosed with ALS who experience some hand weakness but can still move their fingers to some extent. As an unphased trial, it offers a unique opportunity to contribute to groundbreaking research that could improve hand function in ALS patients.

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 prior data suggests that this protocol is safe for ALS patients?

Research has shown that spinal cord associative plasticity (SCAP) and exercises for the arms and hands may help treat amyotrophic lateral sclerosis (ALS). SCAP involves stimulating the brain and spinal cord to strengthen nerve connections. Studies suggest these methods might help ALS patients maintain hand strength. Although detailed safety information for SCAP in humans remains limited, similar techniques have been used safely in other contexts.

For exercises involving the arms and hands, research indicates they can improve function and quality of life for people with ALS. These exercises are generally safe and well-tolerated. So far, no serious safety concerns have arisen for either approach, making them promising for further study. ^{1 2 3 4 5}

Why are researchers excited about this trial?

Researchers are excited about the SCAP and hand exercises for ALS because they offer a fresh approach to tackling this challenging condition. Unlike typical ALS treatments that mainly focus on managing symptoms, SCAP aims to enhance the brain and spinal cord's ability to rewire itself, potentially improving motor function. The combination of SCAP with task-oriented exercises is particularly promising as it could actively help patients regain some upper body movement by strengthening the connections between the brain and muscles. This novel approach could offer new hope for improving quality of life for those living with ALS.

What evidence suggests that this trial's treatments could be effective for ALS?

Research has shown that Spinal Cord Associative Plasticity (SCAP), which participants in this trial may receive, can strengthen weak nerve pathways in people with ALS. This method uses electrical signals to improve the connection between the brain and spinal cord. Previous studies found that SCAP can temporarily boost nerve signals and movement abilities. Upper extremity exercises, another treatment option in this trial, focus on maintaining hand and arm function. Although results on their effectiveness vary, some studies suggest they can enhance quality of life. This trial will test SCAP alone and in combination with these exercises, potentially offering a new way to support hand strength and function in ALS patients. ^{2 5 6 7 8}

Who Is on the Research Team?

Noam Y Harel, MD PhD

Principal Investigator

James J. Peters Veterans Affairs Medical Center

Are You a Good Fit for This Trial?

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.

Timeline for a Trial Participant

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

What Are the Treatments Tested in This Trial?

Interventions

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

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.

How Is the Trial Designed?

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+

Published Research Related to This Trial

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]

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]

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]

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]

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]

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]

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]

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]

Citations

1. labs.icahn.mssm.edu labs.icahn.mssm.edu/harellab/spinal-cord-associative-plasticity-for-amyotrophic-lateral-sclerosis/

Spinal Cord Associative Plasticity for Amyotrophic Lateral ... This is a research study testing for temporary changes in nerve transmission and volitional motor function. This is not a cure for ALS.

2. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC10980254/

Current perspectives on neuromodulation in ALS patients This technique utilizes transcutaneous electrical stimulation, targeting the cervical spinal nerves and associated neural pathways to modulate ...

3. research.va.gov research.va.gov/about/funded_research/proj-details-FY2025.cfm?pid=791367

I01RX004258-01A2 - Spinal Cord Associative Plasticity for ... Title: Spinal Cord Associative Plasticity for Amyotrophic Lateral Sclerosis ; Principal Investigator: Noam Y Harel ; Location: Bronx, NY.

4. ninds.nih.gov ninds.nih.gov/health-information/clinical-trials/spinal-cord-associative-plasticity-study

Spinal Cord Associative Plasticity Study The goal of this project is to translate a promising therapy for improving arm and hand function after partial spinal cord injury to humans. The approach ...

5. sciencedirect.com sciencedirect.com/science/article/pii/S1935861X23019514

Cortico-spinal tDCS in amyotrophic lateral sclerosis Our research group has conducted a study that demonstrated the effectiveness of a two-week treatment with cortico-spinal tDCS, which involves concurrent ...

6. centerwatch.com centerwatch.com/clinical-trials/listings/NCT06172621/spinal-cord-associative-plasticity-for-als?mp=empty&page=5&id=160&slug=amyotrophic-lateral-sclerosis-als

Spinal Cord Associative Plasticity for ALS The investigators have shown that synchronized stimulation over the brain and cervical spinal cord can temporarily strengthen weakened nerve ...

7. sciencedirect.com sciencedirect.com/science/article/pii/S1388245719313598

Posteroanterior cervical transcutaneous spinal stimulation ... No safety data were reported in that study, which focused exclusively on healthy young volunteers. Electrical stimulation targeted at the cervical cord may ...

8. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC9495504/

Non-Invasive Transcutaneous Spinal DC Stimulation as a ... A novel non-invasive transcutaneous sDCS (tsDCS) treatment paradigm on un-anesthetized SOD1-G93A mice. The primary outcomes were motor function and survival.