Direct Current Stimulation for ALS

(CALM Trial)

Overseen By Nader Yaghoubi (Study PI), M.D., Ph.D.

Age: 18+

Sex: Any

Trial Phase: Academic

Sponsor: PathMaker Neurosystems Inc.

Must be taking: Riluzole, Radicava, Qualsody

Disqualifiers: Permanent ventilation, Bulbar ALS, others

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

Compensation: Varies

Number of Visits: 16

Duration: 4 weeks

15 Participants Needed

Trial Summary

Will I have to stop taking my current medications?

The trial requires that you stop using botulinum toxin, phenol or alcohol injections, intrathecal baclofen, digitalis, and morphine during the study. However, you can continue taking a stable dose of rilutek (Riluzole), edaravone (Radicava), tofersen (Qualsody), and certain oral medications for muscle spasms or cramps if you have been on them for at least 30 days before starting the study.

What data supports the effectiveness of the treatment Multi-site direct current stimulation (DCS) for ALS?

Research suggests that direct current stimulation (DCS) can modulate motor neuron activity, which is important in ALS. While studies in mice show potential benefits, such as delayed disease markers and enhanced neuron excitability, human studies are still limited and preliminary. ^{1 2 3 4 5}

Is direct current stimulation safe for humans?

Transcranial direct current stimulation (tDCS) has been explored for safety and feasibility in individuals with ALS, but studies are limited. While some research suggests potential benefits, the evidence is still preliminary, and more studies are needed to fully understand its safety in humans. ^{1 3 4 5 6}

How does the treatment of multi-site direct current stimulation (DCS) for ALS differ from other treatments?

Multi-site direct current stimulation (DCS) for ALS is unique because it uses electrical currents to modulate the activity of motor neurons, potentially improving their function and slowing disease progression. Unlike traditional drug treatments, this non-invasive approach targets the nervous system directly and may offer a complementary method to manage ALS symptoms. ^{1 2 3 4 5}

What is the purpose of this trial?

Following completion of the ALS Early Feasibility Study of the MyoRegulator® device for treatment of ALS (NCT06165172), the CALM study will further assess the feasibility of the MyoRegulator® device to treat ALS in an expanded number of individuals with ALS. CALM will gather additional preliminary evidence of clinical safety and potential effectiveness in this patient population with a longer follow-up period and additional secondary endpoints in a single-arm study prior to commencing a larger sham-controlled pivotal trial.

Eligibility Criteria

This trial is for individuals with ALS, a type of motor neuron disease. Participants should have completed the previous MyoRegulator® device study (NCT06165172) and are now part of an expanded group to further assess treatment feasibility with longer follow-up.

Inclusion Criteria

I have been diagnosed with ALS.

I've been on a stable dose of my ALS medication and muscle spasm treatments for at least 30 days.

Willing to refrain from participation in any other therapeutic clinical trial for the duration of this study

Exclusion Criteria

Implanted intrathecal pump

I use a ventilator for more than 22 hours a day for over a week.

My ALS affects only my speech and swallowing.

Timeline

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants receive active MyoRegulator® device treatment three times per week

4 weeks

12 visits (in-person)

Follow-up

Participants are monitored for safety and effectiveness after treatment

28 weeks

4 visits (in-person) at 1 week, 1 month, 3 months, and optionally at 6 months

Treatment Details

Interventions

• Multi-site direct current stimulation (DCS)

Trial Overview The CALM study tests the MyoRegulator® device's safety and potential effectiveness in treating ALS. It's a single-arm study, meaning all participants receive the actual intervention without a comparison group receiving a placebo.

Participant Groups

Group I: Active MyoRegulator Treatment Arm Experimental Treatment 1 Intervention

4 weeks of active MyoRegulator® device treatment three times per week then follow-up at 1 week, 1 month, 3 months, and optionally at 6 months following the end of treatment

Who Is Running the Clinical Trial?

PathMaker Neurosystems Inc.

Lead Sponsor

Trials

5

Recruited

120+

Beth Israel Deaconess Medical Center

Collaborator

Trials

872

Recruited

12,930,000+

Findings from Research

Spinal direct current stimulation (sDCS) shows promise as a neurorehabilitation therapy for amyotrophic lateral sclerosis (ALS) by modulating motoneuron excitability, but the pilot study faced challenges in applying effective stimulation intensities non-invasively due to skin damage concerns.

The study suggests that while anodal stimulation may be harmful at symptom onset in ALS, cathodal stimulation could be beneficial if higher intensities can be safely achieved, indicating a need for further research into optimal stimulation methods.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Non-Invasive Transcutaneous Spinal DC Stimulation as a Neurorehabilitation ALS Therapy in Awake G93A Mice: The First Step to Clinical Translation. Highlander, MM., Elbasiouny, SM.[2022]

The triple stimulation technique (TST) effectively identified upper motor neuron (UMN) dysfunction in 89.3% of ALS patients with clinical UMN signs, indicating its high sensitivity for detecting UMN involvement.

TST also revealed UMN abnormalities in ALS patients without clinical signs, suggesting it can detect subclinical issues, making it a valuable tool for early diagnosis and assessment of UMN dysfunction in ALS and potentially other conditions.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Triple Stimulation Technique in Amyotrophic Lateral Sclerosis. Wang, Y., Wang, H., Cui, LY.[2019]

In presymptomatic ALS mice, motoneurons (MNs) show reduced excitability and impaired excitatory inputs, particularly affecting large MNs that control fast contracting muscle fibers, which are most vulnerable in ALS.

Trans-spinal direct current stimulation (tsDCS) has shown promise in enhancing MN excitability and synaptic inputs, suggesting that chronic application of anodal tsDCS could be a beneficial complementary treatment for managing ALS.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Is there hope that transpinal direct current stimulation corrects motoneuron excitability and provides neuroprotection in amyotrophic lateral sclerosis? Bączyk, M., Krutki, P., Zytnicki, D.[2022]

Neuromodulation techniques, particularly non-invasive brain stimulation (NIBS) like rTMS and tDCS, show potential in slightly slowing disease progression in amyotrophic lateral sclerosis (ALS) by targeting motor cortical hyperexcitability, which is linked to neurodegeneration.

Current evidence from small trials suggests that the efficacy of these interventions varies based on the type, duration, and frequency of treatment, but the overall findings remain preliminary due to limitations such as small sample sizes and a lack of understanding of the underlying mechanisms involved.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Brain Stimulation as a Therapeutic Tool in Amyotrophic Lateral Sclerosis: Current Status and Interaction With Mechanisms of Altered Cortical Excitability. Ranieri, F., Mariotto, S., Dubbioso, R., et al.[2021]

The study found that long-term transcranial direct current stimulation (tDCS) is safe and feasible for a 36-year-old male with amyotrophic lateral sclerosis (ALS), with no adverse events reported during the 12 sessions of stimulation.

Anodal tDCS resulted in a small but notable improvement in gait speed (15% increase), suggesting potential benefits for motor function in ALS patients, although further research is needed to confirm these effects.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Safety and feasibility of transcranial direct current stimulation in amyotrophic lateral sclerosis - a pilot study with a single subject experimental design. Madhavan, S., Sivaramakrishnan, A., Bond, S., et al.[2019]

Trans-spinal direct current stimulation (tsDCS) can enhance excitatory postsynaptic potentials (EPSPs) in spinal motoneurons of presymptomatic SOD1 G93A mice, suggesting a potential therapeutic effect for ALS, as the facilitation lasted for at least 1 hour after stimulation.

While both SOD1 and wildtype mice experienced short-term EPSP facilitation from anodal tsDCS, only SOD1 mice showed changes in Ia afferent activity and passive membrane properties, indicating that SOD1 motoneurons are particularly sensitive to this neuromodulation technique.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Differential Effects of Invasive Anodal Trans-spinal Direct Current Stimulation on Monosynaptic Excitatory Postsynaptic Potentials, Ia Afferents Excitability, and Motoneuron Intrinsic Properties Between Superoxide Dismutase Type-1 Glycine to Alanine Substitution at Position 93 and Wildtype Mice. Jankowiak, T., Cholewiński, M., Bączyk, M.[2022]

References

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

Non-Invasive Transcutaneous Spinal DC Stimulation as a Neurorehabilitation ALS Therapy in Awake G93A Mice: The First Step to Clinical Translation. [2022]

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

Triple Stimulation Technique in Amyotrophic Lateral Sclerosis. [2019]

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

Is there hope that transpinal direct current stimulation corrects motoneuron excitability and provides neuroprotection in amyotrophic lateral sclerosis? [2022]

4. Switzerland pubmed.ncbi.nlm.nih.gov

Brain Stimulation as a Therapeutic Tool in Amyotrophic Lateral Sclerosis: Current Status and Interaction With Mechanisms of Altered Cortical Excitability. [2021]

5. England pubmed.ncbi.nlm.nih.gov

Safety and feasibility of transcranial direct current stimulation in amyotrophic lateral sclerosis - a pilot study with a single subject experimental design. [2019]

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

Differential Effects of Invasive Anodal Trans-spinal Direct Current Stimulation on Monosynaptic Excitatory Postsynaptic Potentials, Ia Afferents Excitability, and Motoneuron Intrinsic Properties Between Superoxide Dismutase Type-1 Glycine to Alanine Substitution at Position 93 and Wildtype Mice. [2022]