Controlling Amyotrophic Lateral Sclerosis Motor Neuron Excitability Study

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 RCT.

Amyotrophic lateral sclerosis (ALS, Lou Gehrig's disease) is a progressive neurodegenerative disease that affects motor neurons in spinal cord and brain. ALS causes motor and cognitive function deficits and eventual death, typically within 2-5 years of diagnosis. There are at least 30,000 ALS patients in the United States and about 5,000 new diagnoses every year according to the Centers for Disease Control (CDC).

Central features of ALS pathology include the development of motor neuron hyperexcitability and the formation of protein aggregates in the cytoplasmic compartment of motor neurons and these are found across different ALS variants. The MyoRegulator® treatment is a non-invasive neuromodulation-based intervention that suppresses motor neuron hyperexcitability and activates protein degradation pathways through the use of multi-site direct current stimulation (multi-site DCS). Pre-clinical studies show that treatment using multi-site DCS effectively slows disease progression in transgenic mouse models of ALS. This is associated with improved motor function, preservation of motor neurons, and improved animal survival.

This clinical study is a non-significant risk (NSR), single-site, open-label investigation using the non-invasive multi-site DCS MyoRegulator® to evaluate the feasibility and safety of treatment with MyoRegulator® in individuals with ALS and to provide initial evidence of efficacy. The primary endpoint is feasibility and safety. Feasibility will be evaluated by recording and assessing the proportion potential participants who are enrolled from the total number of participants screened for the study, the ease of delivering treatment, the tolerability of study participants to the treatment, and the compliance of study participants with the study schedule and evaluations. Safety will be evaluated by recording the frequency and duration of any adverse events reported by study participants or observed by physical examination during or following treatment and throughout the study duration.

Eligibility Criteria:
Inclusion Criteria:

1. 18-80 years of age inclusive
2. Sporadic or familial ALS diagnosed as clinically possible, probable, lab-supported probable, or definite ALS as defined by revised El Escorial criteria
3. Less than or equal to 24 months since ALS symptom onset
4. Slow Vital Capacity ≥ 50% of predicted capacity at the time of Screening as determined using a portable spirometer
5. For TMS: a resting motor threshold, (defined as the minimum intensity to elicit a motor evoked potential (MEP) of amplitude ≥ 50 μV from at least 5 of 10 consecutive pulses)
6. For TTNCS: Median CMAP ≥ 1.5 mV
7. Willing to forgo botulinum toxin, phenol or alcohol injections, intrathecal baclofen, digitalis, and morphine for the study duration
8. Willing to refrain from participation in any other therapeutic clinical trial or investigational product for ALS for the duration of this study
9. Women must not be able to become pregnant (e.g., post-menopausal, surgically sterile, or using adequate birth control methods) for the duration of the study and 3 months after study completion.
10. Stable dose of rilutek (Riluzole), edaravone (Radicava), or tofersen (Qualsody) and oral medications for muscle spasms/cramps (e.g. mexiletine, quinine, quinidine, magnesium, gabapentin, oxcarbazepine, baclofen) for at least 30 days prior to the onset of participation in the study
11. ALS Functional Rating Score (ALSFRS-R) of greater than or equal to 35
12. Willing and able to give informed consent

Exclusion Criteria:

1. Study participants who are on permanent assisted ventilation (PAV) defined as \>22h of noninvasive or invasive ventilation a day for \> 7 consecutive days.
2. Study participants who have been diagnosed with ALS having only clinical bulbar involvement
3. Implanted intrathecal pump
4. Prior botulinum toxin injection(s) at any site within 12 weeks of study enrollment
5. Prior phenol or alcohol injections for spasticity within 6 months of study enrollment
6. Presence of potential tsDCS and/or TMS risk factors:

   1. Damaged skin at the stimulation sites (i.e., skin with ingrown hairs, acne, razor nicks, wounds that have not healed, recent scar tissue, broken skin, etc.)
   2. Presence of an electrically, magnetically or mechanically activated implant (including cardiac pacemaker) or any other electrically sensitive support system with the exception of loop recorders
   3. Ferromagnetic metal in the head, neck or any site of stimulation including, but not limited to, aneurysm clips, implanted medication pumps, implanted brain stimulators, pacemakers, cochlear implants, implanted metal prostheses or metal due to any injury; dental fillings are permitted. Jewelry must be removed during stimulation
   4. Seizures or unexplained spells of loss of consciousness during the previous 12 months
   5. Any cardiac abnormality that may be exacerbated by transthoracic electrical stimulation
   6. History of cord lesions or previous spinal surgery that may interfere with procedure as determined by the study MD
   7. History of intracranial brain lesions, cortical stroke or previous neurosurgery that may interfere with TMS (e.g., in regions to be stimulated for TMS evaluations) as reviewed and approved by the study MD
7. Any medical condition that would prevent the participant from being able to participate in the clinical outcome measures
8. Pregnant females, as determined by a pregnancy test at V1 (in females of child-bearing potential)