Amyotrophic Lateral SclerosisNCT03411863
Cervical Electrical Stimulation for ALS
A study testing CES at rest and CES plus active hand or wrist movements 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). ALS causes degeneration of motor neurons in both the brain and the spinal cord. Read more about this study
- Who is it for?
- Ages 21 to 75 yearsHealthy volunteers can take part
- Conditions the study is for
- Amyotrophic Lateral Sclerosis
- What is being tested?
- CES at rest and CES plus active hand or wrist movements
- Type of treatment
- Medical device
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 19 participants
- Where
- 1 siteUnited States
- Study dates
- 4 Jan 2018to 1 Jun 2021
- Phase
- Interventional
- Are there results?
- Yes, posted in the registrySummary in the doctors' view
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 21 to 75 years
- All sexes
- Healthy volunteers accepted
- Adult, Older adult
Who may be able to join
- Age between 21 and 75 years
- Diagnosis of probable or definite ALS (or non-disabled volunteer)
- Incomplete weakness of left or right wrist or hand muscles:
- score of 2, 3, or 4 (out of 5) on manual muscle testing of:
- wrist flexion
- finger extension
Show all 15Show fewer
- finger flexion
- or finger abduction
- Detectable F-wave responses of the left or right abductor pollicis brevis (APB) to median nerve stimulation and/or adductor digiti minimi (ADM) to ulnar nerve stimulation
- US Veteran or non-Veteran
- Inclusion Criteria (Participants without neurological disease):
- Age between 21 and 75 years
- No history of significant neurological disease
- Detectable F-wave responses of the left or right APB to median nerve stimulation and/or ADM to ulnar nerve stimulation
- US Veteran or non-Veteran
Who cannot join
- History of other serious injury or disease of central or peripheral nervous system
- History of seizures
- Ventilator dependence or patent tracheostomy site
- Use of medications that significantly lower seizure threshold
- History of head trauma with evidence of brain contusion or hemorrhage or depressed skull fracture on prior imaging
- History of implanted:
Show all 33Show fewer
- brain/spine/nerve stimulators
- aneurysm clips
- ferromagnetic metallic implants
- or cardiac pacemaker/defibrillator
- Significant coronary artery or cardiac conduction disease
- History of bipolar disorder or suicide attempt or active psychosis
- Heavy alcohol consumption (> equivalent of 5 oz of liquor) within previous 48 hours
- Open skin lesions over the face, neck, shoulders, or arms
- Pregnancy
- Unsuitable for study participation as determined by study physician
- Exclusion Criteria: (Participants without neurological disease)
- History of other serious injury or disease of central or peripheral nervous system
- History of seizures
- Ventilator dependence or patent tracheostomy site
- Use of medications that significantly lower seizure threshold
- History of head trauma with 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
- or cardiac pacemaker/defibrillator
- Significant coronary artery or cardiac conduction disease
- History of bipolar disorder or suicide attempt or active psychosis
- Heavy alcohol consumption (> equivalent of 5 oz of liquor) within previous 48 hours
- Open skin lesions over the face, neck, shoulders, or arms
- Pregnancy
- Unsuitable for study participation as determined by study physician
Trial locations and contacts
1 site in 1 country.
United States1 site
James J. Peters VA Medical Center, Bronx, NY
The Bronx, New York, 10468
About this study
Official title: Noninvasive Cervical Electrical Stimulation for ALS: Mechanistic and Safety Study
Veterans are at higher risk than non-Veterans of falling ill with amyotrophic lateral sclerosis (ALS). ALS causes degeneration of motor neurons in both the brain and the spinal cord. Evidence from studies in people with spinal cord injury suggests that activating spared nerve circuits with electromagnetic stimulation improves nerve transmission.
With this goal, the investigators have developed a novel method of noninvasive cervical (neck) electrical stimulation (CES). In this study, the investigators will investigate CES for its potential to strengthen nerve circuits to the hands in ALS.
Read more
To the investigators' knowledge, electrical spinal stimulation for ALS has never been tested previously. This study will be performed in two stages: First, basic experiments will be performed to better understand how CES interacts with other types of electrical and magnetic stimulations over the brain and peripheral nerves. Second, experiments will be performed to determine the types of CES that can facilitate active arm and hand movements.
These experiments will improve understanding of electrical stimulation in ALS, and may set the table for future treatments.
Both United States Veterans and non-Veterans are eligible to participate in this study.
Read the detailed description
Amyotrophic lateral sclerosis (ALS) reduces connections between the cortical motor neurons that initiate movement and the spinal motor neurons that direct muscles to execute movement. This situation shares many key features with incomplete spinal cord injury (SCI). Accumulating evidence in SCI suggests that externally activating spared nerve circuits with electromagnetic stimulation augments neural transmission.
With this goal, the investigators developed a novel method of noninvasive cervical electrical stimulation (CES). CES activates multiple muscles on both upper limbs by triggering afferent sensory or efferent motor nerve roots depending on stimulus intensity. This study will investigate CES for its potential to strengthen residual circuits to the hands in ALS.
To the investigators' knowledge, electrical spinal stimulation for ALS has never been tested or applied previously. Therefore, a pilot study is essential. This study will be performed in two stages:
- Map CES circuit and synaptic targets: The experiments share a common structure comprising conditioning and test stimuli delivered at a range of intensities, sites, and interstimulus intervals.
- Determine parameters for combining CES with volitional movement: volitional limb movements depend on the same corticospinal and motor neuron circuits as those activated by TMS and F-waves. Since preliminary data shows that subthreshold CES facilitates transcranial magnetic stimulation (TMS) responses, CES may also be able to facilitate volitional limb movements.
Successful completion of these experiments will: mechanistically elucidate CES circuit interactions; investigate the potential for CES to enhance concurrent volitional muscle activation; and establish CES as safe and feasible in the ALS population. Given the limited treatment options for ALS, any amount of progress would represent a meaningful step forward. Moreover, results of this pilot study could lead to direct translation for lasting clinical benefit by combining repetitive subthreshold CES with repetitive task-oriented physical exercise training in subsequent studies. CES would be compatible with other interventions, including medications and cell-based treatments.
- Conditions
- Amyotrophic Lateral Sclerosis
- Being tested
- CES at rest, CES plus active hand or wrist movements
- Keywords
- Transcutaneous Electric Nerve Stimulation, 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.
CES at restDevice
CES will be delivered at rest at various intensities, in combination with either electrical stimulation over peripheral nerves or magnetic stimulation over the motor cortex.
This is an experiment designed to measure CES interactions with other central and peripheral nerve circuits.
CES plus active hand or wrist movementsDevice
CES will be delivered while the participant performs specific finger or wrist tasks at different degrees of effort.
This is an experiment designed to detect momentary changes in muscle function.
| Study group | Role | What they receive |
|---|---|---|
| Participants without neurological disease | Active comparator | Participants without neurological disease. All subjects undergo the same full protocol. Receives: Device: CES at rest; Device: CES plus active hand or wrist movements |
| Participants with ALS | Experimental | Participants with ALS. All subjects undergo the same full protocol. Receives: Device: CES at rest; Device: CES plus active hand or wrist movements |
What is being measured
The primary outcome is the main question the study is designed to answer.
Electromyographic (EMG) Responses (Rest)
These results are derived from peak-to-peak EMG amplitude in the abductor pollicis brevis (APB) muscle in response to transcranial magnetic stimulation (TMS). Values represent the ratio of peak-to-peak APB amplitude when TMS is paired with cervical electrical stimulation (CES) at the indicated timing (in milliseconds) normalized to the response to TMS alone (control).
Measured: up to 1 day
Electromyographic Responses (Active)
Effect of CES on concurrent finger or wrist active movements will be measured via root-mean-square of ongoing muscle activity in various hand and forearm muscles.
Measured: up to 1 day
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted26 Jan 2018
- Study start4 Jan 2018
- Primary completion1 Jun 2021
- Study completion1 Jun 2021
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Posted resultsParticipant flow, outcome measures and adverse events reported by the sponsor.
- 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
- Basic science
- Allocation
- Non-randomised
- Intervention model
- Single group
- Masking
- None (open label)
- Enrolment
- 19 participants (actual)
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
- NCT03411863
- Sponsor's protocol ID
- B2527-P
- Status last verified
- Sep 2022
- First submitted
- 5 Jan 2018
- Last updated
- 25 Oct 2022
- Results posted
- Yes, on ClinicalTrials.gov
- Data monitoring committee
- No
- FDA-regulated drug
- No
- FDA-regulated device
- Yes
- Individual data sharing
- Yes: A Limited Dataset (LDS), with individual electrophysiological and physiological outcome measures, will be shared in electronic format pursuant to a VA-approved Data Use Agreement. Individually Identifiable Data will be shared pursuant to valid HIPAA Authorization, Informed Consent, and an appropriate written agreement limiting use of the data to the conditions as described in the authorization and consent, and a written assurance from the recipient that the information will be maintained in accordance with the security requirements of 38 Code of Federal Regulations (CFR) Part 1.466.
Study at a glance
From the registry record, last updated by the sponsor on 25 Oct 2022. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Noninvasive Cervical Electrical Stimulation for ALS: Mechanistic and Safety Study
- ClinicalTrials.gov ID
- NCT03411863
- Acronym / sponsor ID
- B2527-P
- Conditions
- Amyotrophic Lateral Sclerosis
- Keywords
- Transcutaneous Electric Nerve Stimulation, transcranial magnetic stimulation
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 19 participants (actual)
- Lead sponsor
- VA Office of Research and DevelopmentUS federal agency
- Study start
- 4 Jan 2018 (actual)
- Primary completion
- 1 Jun 2021 (actual)
- Study completion
- 1 Jun 2021 (actual)
- First posted
- 26 Jan 2018 (actual)
- Results
- Posted 25 Oct 2022
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). ALS causes degeneration of motor neurons in both the brain and the spinal cord. Evidence from studies in people with spinal cord injury suggests that activating spared nerve circuits with electromagnetic stimulation improves nerve transmission.
With this goal, the investigators have developed a novel method of noninvasive cervical (neck) electrical stimulation (CES). In this study, the investigators will investigate CES for its potential to strengthen nerve circuits to the hands in ALS.
To the investigators' knowledge, electrical spinal stimulation for ALS has never been tested previously. This study will be performed in two stages: First, basic experiments will be performed to better understand how CES interacts with other types of electrical and magnetic stimulations over the brain and peripheral nerves. Second, experiments will be performed to determine the types of CES that can facilitate active arm and hand movements.
These experiments will improve understanding of electrical stimulation in ALS, and may set the table for future treatments.
Both United States Veterans and non-Veterans are eligible to participate in this study.
Detailed description
Amyotrophic lateral sclerosis (ALS) reduces connections between the cortical motor neurons that initiate movement and the spinal motor neurons that direct muscles to execute movement. This situation shares many key features with incomplete spinal cord injury (SCI). Accumulating evidence in SCI suggests that externally activating spared nerve circuits with electromagnetic stimulation augments neural transmission.
With this goal, the investigators developed a novel method of noninvasive cervical electrical stimulation (CES). CES activates multiple muscles on both upper limbs by triggering afferent sensory or efferent motor nerve roots depending on stimulus intensity. This study will investigate CES for its potential to strengthen residual circuits to the hands in ALS.
To the investigators' knowledge, electrical spinal stimulation for ALS has never been tested or applied previously. Therefore, a pilot study is essential. This study will be performed in two stages:
- Map CES circuit and synaptic targets: The experiments share a common structure comprising conditioning and test stimuli delivered at a range of intensities, sites, and interstimulus intervals.
- Determine parameters for combining CES with volitional movement: volitional limb movements depend on the same corticospinal and motor neuron circuits as those activated by TMS and F-waves. Since preliminary data shows that subthreshold CES facilitates transcranial magnetic stimulation (TMS) responses, CES may also be able to facilitate volitional limb movements.
Successful completion of these experiments will: mechanistically elucidate CES circuit interactions; investigate the potential for CES to enhance concurrent volitional muscle activation; and establish CES as safe and feasible in the ALS population. Given the limited treatment options for ALS, any amount of progress would represent a meaningful step forward. Moreover, results of this pilot study could lead to direct translation for lasting clinical benefit by combining repetitive subthreshold CES with repetitive task-oriented physical exercise training in subsequent studies. CES would be compatible with other interventions, including medications and cell-based treatments.
Study design
- Primary purpose
- Basic science
- Allocation
- Non-randomised
- Intervention model
- Single group
- Masking
- None (open label)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| Participants without neurological disease | Active comparator | Device: CES at rest, Device: CES plus active hand or wrist movementsParticipants without neurological disease. All subjects undergo the same full protocol. |
| Participants with ALS | Experimental | Device: CES at rest, Device: CES plus active hand or wrist movementsParticipants with ALS. All subjects undergo the same full protocol. |
Who may qualify
- Ages
- 21 to 75 years
- Sex
- All
- Healthy volunteers
- Accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (15 listed)
- Age between 21 and 75 years
- Diagnosis of probable or definite ALS (or non-disabled volunteer)
- Incomplete weakness of left or right wrist or hand muscles:
- Detectable F-wave responses of the left or right abductor pollicis brevis (APB) to median nerve stimulation and/or adductor digiti minimi (ADM) to ulnar nerve stimulation
- US Veteran or non-Veteran
Key exclusion criteria (33 listed)
- History of other serious injury or disease of central or peripheral nervous system
- History of seizures
- Ventilator dependence or patent tracheostomy site
- Use of medications that significantly lower seizure threshold
- History of head trauma with evidence of brain contusion or hemorrhage or depressed skull fracture on prior imaging
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 |
|---|---|---|
| CES at restCES will be delivered at rest at various intensities, in combination with either electrical stimulation over peripheral nerves or magnetic stimulation over the motor cortex. This is an experiment designed to measure CES interactions with other central and peripheral nerve circuits. | Device | Participants with ALS, Participants without neurological disease |
| CES plus active hand or wrist movementsCES will be delivered while the participant performs specific finger or wrist tasks at different degrees of effort. This is an experiment designed to detect momentary changes in muscle function. | Device | Participants with ALS, Participants without neurological disease |
Primary outcome
Electromyographic (EMG) Responses (Rest)
Time frame: up to 1 day
These results are derived from peak-to-peak EMG amplitude in the abductor pollicis brevis (APB) muscle in response to transcranial magnetic stimulation (TMS). Values represent the ratio of peak-to-peak APB amplitude when TMS is paired with cervical electrical stimulation (CES) at the indicated timing (in milliseconds) normalized to the response to TMS alone (control).
Electromyographic Responses (Active)
Time frame: up to 1 day
Effect of CES on concurrent finger or wrist active movements will be measured via root-mean-square of ongoing muscle activity in various hand and forearm muscles.
Results and safety
Loading the posted results from ClinicalTrials.gov…
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 25 Oct 2022.
- Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
- Individual participant dataSharing planned: Yes. A Limited Dataset (LDS), with individual electrophysiological and physiological outcome measures, will be shared in electronic format pursuant to a VA-approved Data Use Agreement. Individually Identifiable Data will be shared pursuant to valid HIPAA Authorization, Informed Consent, and an appropriate written agreement limiting use of the data to the conditions as described in the authorization and consent, and a written assurance from the recipient that the information will be maintained in accordance with the security requirements of 38 Code of Federal Regulations (CFR) Part 1.466.
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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. This study is not recruiting at the moment.
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 CES at rest and CES plus active hand or wrist movements 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 15 inclusion and 33 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: finished, as of the sponsor's last update on 25 Oct 2022. 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?
Yes. Results are posted in the registry (first posted 25 Oct 2022). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Electromyographic (EMG) Responses (Rest) (time frame: up to 1 day). 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 25 Oct 2022.