Amyotrophic Lateral SclerosisNCT06172621
Spinal Cord Associative Plasticity for ALS
A study testing Spinal Cord Associative Plasticity (SCAP) and Upper extremity task-oriented exercise in people with Amyotrophic Lateral Sclerosis, run by VA Office of Research and Development at 1 site in United States.
Trial summary
Veterans are at higher risk than non-Veterans of falling ill with amyotrophic lateral sclerosis (ALS). The investigators have shown that synchronized stimulation over the brain and cervical spinal cord can temporarily strengthen weakened nerve circuits between the brain and hand muscles in people with ALS. Read more about this study
- Who is it for?
- Ages 18 to 80 years
- Conditions the study is for
- Amyotrophic Lateral Sclerosis
- What is being tested?
- Spinal Cord Associative Plasticity (SCAP) and Upper extremity task-oriented exercise
- Type of treatment
- Surgery or procedure
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 32 participants
- Where
- 1 siteUnited States
- Study dates
- 1 Apr 2024to 29 Feb 2028
- 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
- Diagnosis of ALS by Gold Coast Criteria (Shefner et al. 2020) or "definite" or "probable" ALS by revised El Escorial Criteria (Brooks et al. 2000)
- Incomplete weakness: Score of 1, 2, 3, or 4 (out of 5) on manual muscle testing of finger extension, finger flexion, or finger abduction in left or right hand
- TSCS-evoked potential amplitude of at least 25 V in left or right abductor pollicis brevis (APB) or first dorsal interosseous (FDI) muscles with a resting motor threshold of 55 mA or lower
- TMS-evoked potential amplitude of at least 25 V in left or right abductor pollicis brevis (APB) or first dorsal interosseous (FDI) muscles with a resting motor threshold of 65% MSO or lower
Who cannot join
- History of seizures
- Ventilator dependence or patent tracheostomy site
- Use of medications that significantly lower seizure threshold, such as amphetamines and dalfampridine
- History of severe head trauma (evidence of brain contusion or hemorrhage or depressed skull fracture on prior imaging)
- History of implanted brain/spine/nerve stimulators, aneurysm clips, ferromagnetic metallic implants in the head (except for inside mouth); cochlear implants; cardiac pacemaker/defibrillator; intracardiac lines; currently increased intracranial pressure; or other contraindications to brain or spine stimulation
- Significant coronary artery or cardiac conduction disease; heart failure with an ejection fraction of less than 30% or with a New York Heart Association Functional Classification of Class III or IV
Show all 14Show fewer
- History of significant tinnitus
- History of bipolar disorder
- History of suicide attempt
- Active psychosis
- Ongoing illicit drug or alcohol abuse in the past 6 months
- Heavy alcohol consumption (greater than equivalent of 5 ounces of liquor) within previous 48 hours
- Open skin lesions over the neck, shoulders, or arm stimulation or recording sites
- Pregnancy
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
James J. Peters VA Medical Center, Bronx, NY
The Bronx, New York, 10468-3904
Francisco E Castano, MPH, 718-584-9000 ext. 5824, francisco.castano@va.gov
Noam Y Harel, MD PhD, (718) 584-9000 ext. 1742, Noam.Harel@va.gov
About this study
Official title: Spinal Cord Associative Plasticity for Amyotrophic Lateral Sclerosis
Veterans are at higher risk than non-Veterans of falling ill with amyotrophic lateral sclerosis (ALS).
The investigators have shown that synchronized stimulation over the brain and cervical spinal cord can temporarily strengthen weakened nerve circuits between the brain and hand muscles in people with ALS.
Read more
The current proposal will take the next step of individualizing this intervention, then applying it repetitively in an attempt to achieve direct clinical benefit on hand strength and function.
Following an initial 2-3 month period of optimizing the intervention for each individual, the investigators will compare the effects of two-week programs of paired brain-spinal stimulation with or without hand exercises.
Read the detailed description
Amyotrophic lateral sclerosis (ALS) is more prevalent in Veterans than civilians, leading to ALS being considered a Service-Connected condition by the VA. ALS features incomplete degeneration of upper and lower motor neuron pathways within the spinal cord, a circumstance resembling that of spinal cord injury (SCI). Transcutaneous spinal cord stimulation (TSCS) has demonstrated remarkable potential to activate damaged circuits after SCI to improve motor and autonomic function.
Partly funded by a prior VA award (RX002527), the investigators have preliminary data demonstrating that pairing subthreshold cervical TSCS pulses with suprathreshold transcranial magnetic stimulation (TMS) pulses can enhance hand muscle motor evoked potentials when the cortical pulse reaches the cervical spinal cord 0-5 milliseconds prior to the spinal pulse. This evidence for immediate facilitation of the response to one pair of pulses suggests that if given repetitively, this approach could mediate spinal cord associative plasticity (SCAP) outlasting the period of paired stimulation. The investigators propose that increasing neural plasticity in this manner could be applied as a method to strengthen volitional (cortical) motor output and/or to 'prime' weakened circuits for improved responses to task-oriented exercise.
Both exercise and neuromodulation are understudied in ALS. Though not likely to cure the underlying disease mechanism, these approaches have the potential to mediate symptomatic benefit. The investigators strive to find better ways to conduct disease-oriented research that may provide direct clinical benefit to research participants with ALS and simultaneously increase scientific understanding. Additionally, most ALS clinical study entry criteria heavily favor those at earlier stages of disease. Strict entry criteria are understandable from the scientific perspective. However, we have repeatedly observed the frustration and rejection felt by individuals with ALS who cannot enter clinical trials. This proposed study does not restrict entry by time since symptom onset. The investigators thereby hope to produce more generalizable knowledge by performing a phased study:
- Optimization: SCAP synaptic pairing interval and repetitive frequency pattern will be individually optimized to enhance hand muscle excitability and dexterity. The investigators hypothesize that pairs of stimuli with TMS arriving at the cervical spinal cord up to 2 ms prior to TSCS, delivered in an 'intermittent theta burst' pattern, will produce the strongest facilitation of hand neural circuits.
- Consolidation: Two-week programs of SCAP alone versus SCAP plus task-oriented hand exercise will be compared. The investigators hypothesize that the combined intervention will result in greater and longer lasting physiological and clinical benefits than SCAP by itself.
There are currently no clinical studies in the world involving magnetic brain paired with phasic electrical spinal stimulation for ALS. Therefore, safety needs to be meticulously tracked. Aside from detailed clinical safety measures, the investigators will analyze serum biomarkers drawn at baseline and various stages of the study to better understand whether baseline levels of neurodegenerative, excitotoxic, inflammatory, and neurotropic biomarkers associate with either beneficial or detrimental responses to SCAP and exercise interventions.
- Conditions
- Amyotrophic Lateral Sclerosis
- Being tested
- Spinal Cord Associative Plasticity (SCAP), Upper extremity task-oriented exercise
- Keywords
- neuromodulation, spinal cord stimulation, task-oriented exercise, transcranial magnetic stimulation
- 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.
Spinal Cord Associative Plasticity (SCAP)Procedure or surgery
Paired non-invasive brain and spinal cord stimulation.
Upper extremity task-oriented exerciseProcedure or surgery
Participants will perform a range of exercises composed of tasks resembling daily home/community activities such as stacking and sorting small objects, manipulating writing utensils, keys, buttons, etc.
| Study group | Role | What they receive |
|---|---|---|
| SCAP alone | Active comparator | 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. Receives: Procedure: Spinal Cord Associative Plasticity (SCAP) |
| SCAP plus task-oriented exercise | Experimental | 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. Receives: Procedure: Spinal Cord Associative Plasticity (SCAP); Procedure: Upper extremity task-oriented exercise |
What is being measured
The primary outcome is the main question the study is designed to answer.
Amplitude of intrinsic hand muscle response to single-pulse transcranial magnetic stimulation (TMS)
The primary neurophysiological outcome will be corticospinal excitability measured at the first dorsal interosseous (FDI) muscle. If no suitable FDI muscle, will substitute with abductor pollicis brevis (APB) muscle.
Measured: Through study completion, up to 6 months
Hand dexterity on the nine-hole peg test
Time to complete placement of nine pegs into their respective holes using the target hand.
Measured: Through study completion, up to 6 months
Secondary outcomes (3)
Volitional strength assessed by isometric dynamometry (key-pinch configuration)
Maximal isometric pinch strength will be measured using a pinch dynamometer. Maximum volitional force will be applied for 3-5 seconds, with at least 30 seconds between trials. The highest achieved value will be used for analysis.
Measured: Through study completion, up to 6 months
Volitional strength assessed by isometric dynamometry (tip-to-tip configuration)
Maximal isometric pinch strength will be measured using a pinch dynamometer. Maximum volitional force will be applied for 3-5 seconds, with at least 30 seconds between trials. The highest achieved value will be used for analysis.
Measured: Through study completion, up to 6 months
Volitional strength assessed by isometric dynamometry (grip configuration)
Maximal isometric pinch strength will be measured using a hand dynamometer. Maximum volitional force will be applied for 3-5 seconds, with at least 30 seconds between trials. The highest achieved value will be used for analysis.
Measured: Through study completion, up to 6 months
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted15 Dec 2023
- Study start1 Apr 2024
- Primary completion30 Nov 2027 (estimated)
- Study completion29 Feb 2028 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Amyotrophic Lateral SclerosisStudies of the same condition, open and under way.
- More trials run by VA Office of Research and DevelopmentThe sponsor's other registered studies.
- 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
- Other
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Model description
- After a run-in phase of 2-4 months to determine individualized stimulation parameters, participants will be randomized into Group A and Group B. Group A will undergo 2 weeks (6 sessions) of SCAP alone. Group B will undergo 2 weeks (6 sessions) of SCAP plus upper extremity task-oriented exercise.
- Masking
- Single blind
- Who is masked
- Outcomes assessor
- Enrolment
- 32 participants (estimated)
Sponsor and investigators
- Lead sponsor
- VA Office of Research and Development
- Sponsor type
- US federal agency
- Responsible party
- Sponsor
- Investigators
- Noam Y. Harel, MD PhD, Principal investigator, James J. Peters Veterans Affairs Medical Center
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT06172621
- Sponsor's protocol ID
- B4258-R
- Other IDs
- 1I01RX004258
- Status last verified
- Mar 2026
- First submitted
- 6 Dec 2023
- Last updated
- 20 Mar 2026
- Results posted
- No
- Data monitoring committee
- No
- FDA-regulated drug
- No
- FDA-regulated device
- No
- Individual data sharing
- Yes: Deidentified IPD will be deposited at Open Data Commons for Spinal Cord Injury
Study at a glance
From the registry record, last updated by the sponsor on 20 Mar 2026. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Spinal Cord Associative Plasticity for Amyotrophic Lateral Sclerosis
- ClinicalTrials.gov ID
- NCT06172621
- Acronym / sponsor ID
- B4258-R
- Conditions
- Amyotrophic Lateral Sclerosis
- Keywords
- neuromodulation, spinal cord stimulation, task-oriented exercise, transcranial magnetic stimulation
- Study type
- Interventional
- Recruitment status
- Recruiting
- Enrolment
- 32 participants (estimated)
- Lead sponsor
- VA Office of Research and DevelopmentUS federal agency
- Study start
- 1 Apr 2024 (actual)
- Primary completion
- 30 Nov 2027 (estimated)
- Study completion
- 29 Feb 2028 (estimated)
- First posted
- 15 Dec 2023 (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.
Veterans are at higher risk than non-Veterans of falling ill with amyotrophic lateral sclerosis (ALS).
The investigators have shown that synchronized stimulation over the brain and cervical spinal cord can temporarily strengthen weakened nerve circuits between the brain and hand muscles in people with ALS.
The current proposal will take the next step of individualizing this intervention, then applying it repetitively in an attempt to achieve direct clinical benefit on hand strength and function.
Following an initial 2-3 month period of optimizing the intervention for each individual, the investigators will compare the effects of two-week programs of paired brain-spinal stimulation with or without hand exercises.
Detailed description
Amyotrophic lateral sclerosis (ALS) is more prevalent in Veterans than civilians, leading to ALS being considered a Service-Connected condition by the VA. ALS features incomplete degeneration of upper and lower motor neuron pathways within the spinal cord, a circumstance resembling that of spinal cord injury (SCI). Transcutaneous spinal cord stimulation (TSCS) has demonstrated remarkable potential to activate damaged circuits after SCI to improve motor and autonomic function.
Partly funded by a prior VA award (RX002527), the investigators have preliminary data demonstrating that pairing subthreshold cervical TSCS pulses with suprathreshold transcranial magnetic stimulation (TMS) pulses can enhance hand muscle motor evoked potentials when the cortical pulse reaches the cervical spinal cord 0-5 milliseconds prior to the spinal pulse. This evidence for immediate facilitation of the response to one pair of pulses suggests that if given repetitively, this approach could mediate spinal cord associative plasticity (SCAP) outlasting the period of paired stimulation. The investigators propose that increasing neural plasticity in this manner could be applied as a method to strengthen volitional (cortical) motor output and/or to 'prime' weakened circuits for improved responses to task-oriented exercise.
Both exercise and neuromodulation are understudied in ALS. Though not likely to cure the underlying disease mechanism, these approaches have the potential to mediate symptomatic benefit. The investigators strive to find better ways to conduct disease-oriented research that may provide direct clinical benefit to research participants with ALS and simultaneously increase scientific understanding. Additionally, most ALS clinical study entry criteria heavily favor those at earlier stages of disease. Strict entry criteria are understandable from the scientific perspective. However, we have repeatedly observed the frustration and rejection felt by individuals with ALS who cannot enter clinical trials. This proposed study does not restrict entry by time since symptom onset. The investigators thereby hope to produce more generalizable knowledge by performing a phased study:
- Optimization: SCAP synaptic pairing interval and repetitive frequency pattern will be individually optimized to enhance hand muscle excitability and dexterity. The investigators hypothesize that pairs of stimuli with TMS arriving at the cervical spinal cord up to 2 ms prior to TSCS, delivered in an 'intermittent theta burst' pattern, will produce the strongest facilitation of hand neural circuits.
- Consolidation: Two-week programs of SCAP alone versus SCAP plus task-oriented hand exercise will be compared. The investigators hypothesize that the combined intervention will result in greater and longer lasting physiological and clinical benefits than SCAP by itself.
There are currently no clinical studies in the world involving magnetic brain paired with phasic electrical spinal stimulation for ALS. Therefore, safety needs to be meticulously tracked. Aside from detailed clinical safety measures, the investigators will analyze serum biomarkers drawn at baseline and various stages of the study to better understand whether baseline levels of neurodegenerative, excitotoxic, inflammatory, and neurotropic biomarkers associate with either beneficial or detrimental responses to SCAP and exercise interventions.
Study design
- Primary purpose
- Other
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Single blind (outcomes assessor)
- Number of arms
- 2
- Model description
- After a run-in phase of 2-4 months to determine individualized stimulation parameters, participants will be randomized into Group A and Group B. Group A will undergo 2 weeks (6 sessions) of SCAP alone. Group B will undergo 2 weeks (6 sessions) of SCAP plus upper extremity task-oriented exercise.
| Arm | Type | Receives |
|---|---|---|
| SCAP alone | Active comparator | Procedure: Spinal Cord Associative Plasticity (SCAP)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. |
| SCAP plus task-oriented exercise | Experimental | Procedure: Spinal Cord Associative Plasticity (SCAP), Procedure: Upper extremity task-oriented exerciseAfter 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. |
Who may qualify
- Ages
- 18 to 80 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (4 listed)
- Diagnosis of ALS by Gold Coast Criteria (Shefner et al. 2020) or "definite" or "probable" ALS by revised El Escorial Criteria (Brooks et al. 2000)
- Incomplete weakness: Score of 1, 2, 3, or 4 (out of 5) on manual muscle testing of finger extension, finger flexion, or finger abduction in left or right hand
- TSCS-evoked potential amplitude of at least 25 V in left or right abductor pollicis brevis (APB) or first dorsal interosseous (FDI) muscles with a resting motor threshold of 55 mA or lower
- TMS-evoked potential amplitude of at least 25 V in left or right abductor pollicis brevis (APB) or first dorsal interosseous (FDI) muscles with a resting motor threshold of 65% MSO or lower
Key exclusion criteria (14 listed)
- History of seizures
- Ventilator dependence or patent tracheostomy site
- Use of medications that significantly lower seizure threshold, such as amphetamines and dalfampridine
- History of severe head trauma (evidence of brain contusion or hemorrhage or depressed skull fracture on prior imaging)
- History of implanted brain/spine/nerve stimulators, aneurysm clips, ferromagnetic metallic implants in the head (except for inside mouth); cochlear implants; cardiac pacemaker/defibrillator; intracardiac lines; currently increased intracranial pressure; or other contraindications to brain or spine stimulation
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 |
|---|---|---|
| Spinal Cord Associative Plasticity (SCAP)Paired non-invasive brain and spinal cord stimulation. | Procedure or surgery | SCAP alone, SCAP plus task-oriented exercise |
| Upper extremity task-oriented exerciseParticipants will perform a range of exercises composed of tasks resembling daily home/community activities such as stacking and sorting small objects, manipulating writing utensils, keys, buttons, etc. | Procedure or surgery | SCAP plus task-oriented exercise |
Primary outcome
Amplitude of intrinsic hand muscle response to single-pulse transcranial magnetic stimulation (TMS)
Time frame: Through study completion, up to 6 months
The primary neurophysiological outcome will be corticospinal excitability measured at the first dorsal interosseous (FDI) muscle. If no suitable FDI muscle, will substitute with abductor pollicis brevis (APB) muscle.
Hand dexterity on the nine-hole peg test
Time frame: Through study completion, up to 6 months
Time to complete placement of nine pegs into their respective holes using the target hand.
3 secondary outcomes
Volitional strength assessed by isometric dynamometry (key-pinch configuration)
Time frame: Through study completion, up to 6 months
Volitional strength assessed by isometric dynamometry (tip-to-tip configuration)
Time frame: Through study completion, up to 6 months
Volitional strength assessed by isometric dynamometry (grip configuration)
Time frame: Through study completion, up to 6 months
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 20 Mar 2026.
- Individual participant dataSharing planned: Yes. Deidentified IPD will be deposited at Open Data Commons for Spinal Cord Injury
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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.
Noam Y. Harel, MD PhD principal investigator
James J. Peters Veterans Affairs Medical Center
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A study testing Spinal Cord Associative Plasticity (SCAP) and Upper extremity task-oriented exercise in people with Amyotrophic Lateral Sclerosis, run by VA Office of Research and Development 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 4 inclusion and 14 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 20 Mar 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 Francisco E Castano, MPH ((718) 584-9000 ext. 5824, francisco.castano@va.gov), or a site near the patient. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Amplitude of intrinsic hand muscle response to single-pulse transcranial magnetic stimulation (TMS) (time frame: Through study completion, up to 6 months). 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 20 Mar 2026.