ALS - Amyotrophic Lateral SclerosisCALMNCT06649955
Controlling Amyotrophic Lateral Sclerosis Motor Neuron Excitability Study
A study testing Multi-site direct current stimulation (DCS) in people with ALS - Amyotrophic Lateral Sclerosis, run by PathMaker Neurosystems Inc. at 1 site in United States.
Trial summary
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. Read more about this study
- Who is it for?
- Ages 18 to 80 years
- Conditions the study is for
- ALS - Amyotrophic Lateral Sclerosis
- What is being tested?
- Multi-site direct current stimulation (DCS)
- Type of treatment
- Medical device
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 15 participants
- Where
- 1 siteUnited States
- Study dates
- 10 Feb 2025to Feb 2027
- Phase
- Interventional
- Are there results?
- Not yet: the study is under way
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 to 80 years
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- 18-80 years of age inclusive
- Sporadic or familial ALS diagnosed as clinically possible, probable, lab-supported probable, or definite ALS as defined by revised El Escorial criteria
- Less than or equal to 3 years since ALS symptom onset
- Slow Vital Capacity ≥ 50% of predicted capacity at the time of Screening as determined using a portable spirometer
- For TTNCS: Median CMAP ≥ 1.5 mV
- Willing to forgo botulinum toxin, phenol or alcohol injections, intrathecal baclofen, digitalis, and morphine for the study duration
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- Willing to refrain from participation in any other therapeutic clinical trial or investigational product for ALS for the duration of this study
- 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.
- 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
- ALS Functional Rating Score (ALSFRS-R) of greater than or equal to 35
- Willing and able to give informed consent
Who cannot join
- Study participants who are on permanent assisted ventilation (PAV) defined as >22h of noninvasive or invasive ventilation a day for > 7 consecutive days.
- Study participants who have been diagnosed with ALS having only clinical bulbar involvement
- Implanted intrathecal pump
- Prior botulinum toxin injection(s) at any site within 12 weeks of study enrollment
- Prior phenol or alcohol injections for spasticity within 6 months of study enrollment
- Presence of potential tsDCS and/or TMS risk factors:
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- 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.)
- 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
- 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
- Seizures or unexplained spells of loss of consciousness during the previous 12 months
- Any cardiac abnormality that may be exacerbated by transthoracic electrical stimulation
- History of cord lesions or previous spinal surgery that may interfere with procedure as determined by the study MD
- 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
- Any medical condition that would prevent the participant from being able to participate in the clinical outcome measures
- Pregnant females, as determined by a pregnancy test at V1 (in females of child-bearing potential)
Trial locations and contacts
1 site in 1 country. Contact the study team or a site near you to ask about taking part.
United States1 site, 1 recruiting
- Recruiting
Beth Israel Deaconess Medical Center
Boston, Massachusetts, 02215
Tatyana Okanlomo, 617-667-3083, tokanlom@bidmc.harvard.edu
Seward Rutkove, M.D.
About this 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 pivotal trial.
Read the detailed description
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.
- Conditions
- ALS - Amyotrophic Lateral Sclerosis
- Being tested
- Multi-site direct current stimulation (DCS)
- Keywords
- ALS, Lou Gehrig's disease, Non-invasive, Multi-site direct current stimulation (multi-site DCS)
- Medical subject headings
- Amyotrophic Lateral Sclerosis
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Multi-site direct current stimulation (DCS)Device
The MyoRegulator® treatment is a non-invasive intervention that suppresses motor neuron hyperexcitability and activates protein degradation pathways through the use of multi-site direct current stimulation (multi-site DCS).
| Study group | Role | What they receive |
|---|---|---|
| Active MyoRegulator Treatment Arm | Experimental | 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 Receives: Device: Multi-site direct current stimulation (DCS) |
What is being measured
The primary outcome is the main question the study is designed to answer.
Feasibility of treating ALS patients using multi-site DCS
The feasibility of treating ALS patients using multi-site DCS will be evaluated by determining the number of patients who can complete all of the study treatments at the target stimulation levels:
Measured: On treatment day and at each follow-up visit out to 3 months post-treatment
Incidence of Treatment-Emergent Adverse Events [Safety and Tolerability]
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, with particular attention to any device-related serious adverse events or unanticipated adverse events.
Measured: On treatment day and at each follow-up visit out to 6 months post-treatment
Secondary outcomes (7)
ALS Functional Rating Scale (ALSFRS-R)
The Revised (ALSFRS-R) is a clinician administered outcome measure that provides an evaluation of function in ALS patients. The ALSFRS-R measures 12 aspects of physical function, ranging from one's ability to swallow and use utensils to climbing stairs and breathing. Each function is scored from 4 (normal) to 0 (no ability), with a maximum total score of 48 and a minimum total score of 0.
Measured: Just prior to treatment start at study week 1, after the last treatment at study week 4, then during follow-up at study weeks 8, 16, and 28
Rasch Overall ALS Disability Scale (ROADS)
ROADS is a patient-reported outcome measure used to evaluate functional abilities for activities of daily living in patients with ALS. ROADS is scored by assigning each of its 28 items a value of 0, 1, or 2:
0: Unable to perform the task
- Able to perform the task with difficulty or with assistance
- Able to perform the task without difficulty ROADS then provides a normed total score that ranges from 0 to 146. The normed score is linearly weighted, meaning that a 1-point change represents a consistent and quantifiable measurement of disability. A 2-point change reflects twice the amount of disability.
Measured: Just prior to treatment start at study week 1, after the last treatment at study week 4, then during follow-up at study weeks 8, 16, and 28
ALS Assessment Questionnaire (ALSAQ-40)
The ALSAQ-40 is a patient-reported, 40-item questionnaire that measures five areas of health status (domains) in patients with Amyotrophic Lateral Sclerosis (ALS) or other motor neuron diseases: 1) physical mobility; 2) activities of daily living and independence; 3) eating and drinking; 4) communication; 5), and emotional functioning.
Each item on the ALSAQ-40 is scored using a 5-point Likert scale from 0 to 4. The sum of the item scores for each domain is divided by the maximum possible score for that domain, and then multiplied by 100. A lower score indicates a higher health-related quality of life (HRQoL).
Measured: Just prior to treatment at study week 1, then during follow-up at study weeks 4, 8, 16, and 28
Accurate Test of Limb Isometric Strength (ATLIS)
The ATLIS machine will be used to measure any changes in isometric muscle strength in the study patients over the course of the study.
Measured: At baseline the day prior to treatment start, after the last treatment at study week 4, and at follow-up during weeks 8, 16, and 28
Threshold tracking nerve conduction studies (TTNCS)
TTNCS is used to assess spinal motor neuron excitability.
Measured: At baseline the day prior to treatment start, after the last treatment at study week 4, and at follow-up during weeks 5, 8, 16, and 28
Measurement of cortical motor neuron excitabiity using Trans-cranial magnetic stimulation (TMS)
TMS is used to assess any changes in cortical motor neuron excitability throughout the study compared to baseline. This assessment involves evaluating the motor evoked potential (MEP) and the resting motor threshold (MT) using single-pulse TMS and evaluating intracortical excitability using a paired-pulse technique.
Measured: At baseline the day prior to treatment start, after the last treatment at study week 4, and at follow-up during weeks 5, 8 and 16.
Slow Vital Capacity (SVC)
SVC is used to assess respiratory function.
Measured: At baseline the day prior to treatment start, after the last treatment at study week 4 and at follow-up during weeks 5, 8, 16, and 28
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted21 Oct 2024
- Study start10 Feb 2025
- Primary completionOct 2026 (estimated)
- Study completionFeb 2027 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for ALS - Amyotrophic Lateral SclerosisStudies of the same condition, open and under way.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase N/A
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Enrolment
- 15 participants (estimated)
Sponsor and investigators
- Lead sponsor
- PathMaker Neurosystems Inc.
- Sponsor type
- Industry (pharma, biotech, devices)
- Collaborators
- Beth Israel Deaconess Medical Center, United States Department of Defense
- Responsible party
- Sponsor
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT06649955
- Sponsor's protocol ID
- ALS2
- Other IDs
- CDMRP-AL230079
- Acronym
- CALM
- Status last verified
- Sep 2026
- First submitted
- 14 Oct 2024
- Last updated
- 10 Sep 2026
- Results posted
- No
- Data monitoring committee
- No
- FDA-regulated drug
- No
- FDA-regulated device
- Yes
- Individual data sharing
- No
Study at a glance
From the registry record, last updated by the sponsor on 10 Sep 2026. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Controlling Amyotrophic Lateral Sclerosis Motor Neuron Excitability Study
- ClinicalTrials.gov ID
- NCT06649955
- Acronym / sponsor ID
- CALM / ALS2
- Conditions
- ALS - Amyotrophic Lateral Sclerosis
- Keywords
- ALS, Lou Gehrig's disease, Non-invasive, Multi-site direct current stimulation (multi-site DCS)
- Study type
- Interventional
- Recruitment status
- Recruiting
- Enrolment
- 15 participants (estimated)
- Lead sponsor
- PathMaker Neurosystems Inc.Industry (pharma, biotech, devices)
- Collaborators
- Beth Israel Deaconess Medical Center, United States Department of Defense
- Study start
- 10 Feb 2025 (actual)
- Primary completion
- Oct 2026 (estimated)
- Study completion
- Feb 2027 (estimated)
- First posted
- 21 Oct 2024 (actual)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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.
Detailed description
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.
Study design
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Number of arms
- 1
| Arm | Type | Receives |
|---|---|---|
| Active MyoRegulator Treatment Arm | Experimental | Device: Multi-site direct current stimulation (DCS)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 may qualify
- Ages
- 18 to 80 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (11 listed)
- 18-80 years of age inclusive
- Sporadic or familial ALS diagnosed as clinically possible, probable, lab-supported probable, or definite ALS as defined by revised El Escorial criteria
- Less than or equal to 3 years since ALS symptom onset
- Slow Vital Capacity ≥ 50% of predicted capacity at the time of Screening as determined using a portable spirometer
- For TTNCS: Median CMAP ≥ 1.5 mV
Key exclusion criteria (15 listed)
- Study participants who are on permanent assisted ventilation (PAV) defined as >22h of noninvasive or invasive ventilation a day for > 7 consecutive days.
- Study participants who have been diagnosed with ALS having only clinical bulbar involvement
- Implanted intrathecal pump
- Prior botulinum toxin injection(s) at any site within 12 weeks of study enrollment
- Prior phenol or alcohol injections for spasticity within 6 months of study enrollment
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| Multi-site direct current stimulation (DCS)The MyoRegulator® treatment is a non-invasive intervention that suppresses motor neuron hyperexcitability and activates protein degradation pathways through the use of multi-site direct current stimulation (multi-site DCS). | Device | Active MyoRegulator Treatment Arm |
Primary outcome
Feasibility of treating ALS patients using multi-site DCS
Time frame: On treatment day and at each follow-up visit out to 3 months post-treatment
The feasibility of treating ALS patients using multi-site DCS will be evaluated by determining the number of patients who can complete all of the study treatments at the target stimulation levels:
Incidence of Treatment-Emergent Adverse Events [Safety and Tolerability]
Time frame: On treatment day and at each follow-up visit out to 6 months post-treatment
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, with particular attention to any device-related serious adverse events or unanticipated adverse events.
7 secondary outcomes
ALS Functional Rating Scale (ALSFRS-R)
Time frame: Just prior to treatment start at study week 1, after the last treatment at study week 4, then during follow-up at study weeks 8, 16, and 28
Rasch Overall ALS Disability Scale (ROADS)
Time frame: Just prior to treatment start at study week 1, after the last treatment at study week 4, then during follow-up at study weeks 8, 16, and 28
ALS Assessment Questionnaire (ALSAQ-40)
Time frame: Just prior to treatment at study week 1, then during follow-up at study weeks 4, 8, 16, and 28
Accurate Test of Limb Isometric Strength (ATLIS)
Time frame: At baseline the day prior to treatment start, after the last treatment at study week 4, and at follow-up during weeks 8, 16, and 28
Threshold tracking nerve conduction studies (TTNCS)
Time frame: At baseline the day prior to treatment start, after the last treatment at study week 4, and at follow-up during weeks 5, 8, 16, and 28
Measurement of cortical motor neuron excitabiity using Trans-cranial magnetic stimulation (TMS)
Time frame: At baseline the day prior to treatment start, after the last treatment at study week 4, and at follow-up during weeks 5, 8 and 16.
Slow Vital Capacity (SVC)
Time frame: At baseline the day prior to treatment start, after the last treatment at study week 4 and at follow-up during weeks 5, 8, 16, and 28
Results and safety
This study is still under way. Results are not available in the source record yet.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 10 Sep 2026.
- Individual participant dataSharing planned: No
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part.
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A study testing Multi-site direct current stimulation (DCS) in people with ALS - Amyotrophic Lateral Sclerosis, run by PathMaker Neurosystems Inc. at 1 site in United States.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 11 inclusion and 15 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: looking for participants now, as of the sponsor's last update on 10 Sep 2026. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in United States. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
Are results available for this study?
This study is still under way. Results are not available in the source record yet.
How can a doctor refer a patient or contact the research team?
Contact Seward Rutkove (Clinical Site PI), M.D. (617-667-3083, tokanlom@bidmc.harvard.edu), or a site near the patient. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Feasibility of treating ALS patients using multi-site DCS (time frame: On treatment day and at each follow-up visit out to 3 months post-treatment). The study lists 2 primary outcomes in all. It is what the study was designed to measure, not a finding.
Where can I read the original study information?
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 10 Sep 2026.