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

What You Need to Know Before You Apply

What is the purpose of this trial?

The trial aims to evaluate a device called the MyoRegulator® for individuals with ALS, a condition affecting nerve cells that control muscles. Researchers will use multi-site direct current stimulation, a method involving electrical currents, to determine if it improves symptoms and is safe. Participants will receive treatment three times a week for four weeks and will be monitored for up to six months. The trial seeks individuals who have experienced ALS symptoms for less than three years and are not reliant on a ventilator for most of the day. As an unphased trial, this study offers a unique opportunity to contribute to groundbreaking research and potentially benefit from an innovative treatment.

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 prior data suggests that the MyoRegulator® device is safe for treating ALS?

Research has shown that multi-site direct current stimulation (DCS) for ALS is considered low-risk, indicating it is generally safe for people. Studies have examined the MyoRegulator® device, which uses this type of stimulation. Early animal research, such as studies on mice, suggested that this treatment might slow the disease's progression.

Regarding human safety, earlier studies tested the MyoRegulator® and found it to be well-tolerated, with no major side effects reported. This is encouraging for prospective trial participants, as it suggests the treatment is safe for people. ^{1 2 3 4 5}

Why are researchers excited about this trial?

Researchers are excited about multi-site direct current stimulation (DCS) for ALS because it represents a non-invasive approach that could potentially alter disease progression. Unlike current ALS treatments, which often rely on medications like Riluzole or Edaravone to slow down the disease, DCS involves using the MyoRegulator® device to stimulate muscles directly, which could improve motor function. This technique is unique because it uses electrical currents to target specific body areas, aiming to enhance muscle control and strength, potentially offering benefits beyond what existing drugs provide.

What evidence suggests that the MyoRegulator® device is effective for ALS?

Research suggests that multi-site direct current stimulation (DCS), the treatment participants in this trial will receive, might help people with ALS. Studies using mice with ALS have shown that this treatment can slow the disease and extend lifespan. The therapy calms the nerve cells in the spinal cord, which is crucial because ALS overactivates these cells. Early research indicates that this approach could be promising for people with ALS. ^{1 2 3 6 7}

Are You a Good Fit for This Trial?

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 for a Trial Participant

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

What Are the Treatments Tested in This Trial?

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.

How Is the Trial Designed?

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+

United States Department of Defense

Collaborator

Trials

940

Recruited

339,000+

Published Research Related to This Trial

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]

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]

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]

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]

Citations

1. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC12241670/

Multi-path direct current spinal stimulation extended survival in ... MultiPath-DCS modulates the excitability of spinal cord neurons. This effect is significant for ALS, as motor neuron hyperexcitability is a ...

2. clinicaltrials.gov clinicaltrials.gov/study/NCT06649955

NCT06649955 | Controlling Amyotrophic Lateral Sclerosis ... Pre-clinical studies show that treatment using multi-site DCS effectively slows disease progression in transgenic mouse models of ALS. This is associated with ...

3. trialx.com trialx.com/clinical-trials/listings/227541/early-feasibility-study-of-the-myoregulator-for-treatment-of-als/?&geo_lat=42.3576&geo_lng=-71.0684&radius=10&place=Boston&user_country=United%20States

Early Feasibility Study of the MyoRegulator® for Treatment ... Pre-clinical studies show that treatment using multi-site DCS effectively slows disease progression in transgenic mouse models of ALS.

4. alsnewstoday.com alsnewstoday.com/news/noninvasive-spinal-stimulation-extends-survival-als-mice-study/

Noninvasive spinal stimulation extends survival in ALS mice A noninvasive therapy delivering gentle spinal stimulation was shown to slow disease progression and extend survival in an ALS mouse model.

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

Cortico-spinal tDCS in amyotrophic lateral sclerosis Cortico-spinal tDCS improves strength, caregiver burden, and quality of life in ALS. Real tDCS restores intracortical connectivity and decreases serum ...

6. rally.massgeneralbrigham.org rally.massgeneralbrigham.org/study/als_myoregulator

Electrical Stimulation for ALS We are studying the feasibility and safety of using the MyoRegulator neuromodulation device for multi-site direct current stimulation in people who have ALS.

7. clinicaltrials.gov clinicaltrials.gov/study/NCT06649955?cond=Amyotrophic%20lateral%20sclerosis%20OR%20%22ALS%22%20OR%20%22%20Charcot%20disease%22%20OR%20%22%20Lou%20Gehrig%20disease%22%20OR%20%22%20Lou%20Gehrig's%20disease%22%20OR%20%22%20motor%20neuron%20disease,%20bulbar%22&aggFilters=status:not%20rec&viewType=Table&rank=6

Controlling Amyotrophic Lateral Sclerosis Motor Neuron ... Pre-clinical studies show that treatment using multi-site DCS effectively slows disease progression in transgenic mouse models of ALS. This is associated with ...