Spinal Cord InjuriesNCT03414424
Non-invasive Cervical Electrical Stimulation for SCI
A study testing CES at rest and CES plus active hand or wrist movements in people with Spinal Cord Injuries, run by Bronx VA Medical Center at 1 site in United States.
Trial summary
Most spinal cord injuries (SCI) are anatomically incomplete - some nerve circuits remain intact, even if the individual cannot feel or control them. Activating spared nerve circuits may improve functional recovery. Read more about this study
- Who is it for?
- Ages 18 to 75 yearsHealthy volunteers can take part
- Conditions the study is for
- Spinal Cord Injuries
- 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
- 30 participants
- Where
- 1 siteUnited States
- Study dates
- 22 Aug 2017to 30 Apr 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 18 to 75 years
- All sexes
- Healthy volunteers accepted
- Adult, Older adult
Who may be able to join
- Age between 18 and 75 years;
- Chronic (more than 12 months since injury) incomplete SCI between levels C2-C8.
- Incomplete weakness of left or right hand muscles: score of 2, 3, or 4 (out of 5) on manual muscle testing of finger extension, finger flexion, or finger abduction;
- Detectable F-wave responses of the left or right abductor pollicis brevis muscle to median 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 17Show fewer
- brain/spine/nerve stimulators
- aneurysm clips
- ferromagnetic metallic implants
- or cardiac pacemaker/defibrillator
- Significant coronary artery or cardiac conduction disease
- Recent history (within past 6 months) of recurrent autonomic dysreflexia, defined as a syndrome of sudden rise in systolic pressure greater than 20 mm Hg (millimeters of mercury) or diastolic pressure greater than 10 mm Hg, without rise in heart rate, accompanied by symptoms such as headache, facial flushing, sweating, nasal congestion, and blurry vision (this will be closely monitored during all screening and testing procedures);
- History of bipolar disorder or suicide attempt or active psychosis
- Heavy alcohol consumption (> equivalent of 5 ounces 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
Most spinal cord injuries (SCI) are anatomically incomplete - some nerve circuits remain intact, even if the individual cannot feel or control them. Activating spared nerve circuits may improve functional recovery.
With this goal, the Investigators have developed a form of electrical stimulation over the cervical spinal cord that can activate muscles in both hands simultaneously and comfortably. This technique, called cervical electrical stimulation (CES), works at the skin surface - no surgery or other invasive procedures are required.
Read more
The long-term goal is to use CES to strengthen residual circuits to hand muscles after SCI. Regaining control over hand function represents the top priority for individuals with cervical SCI.
In the current study, the Investigators first need to better understand how CES works. In the first half of this study, the Investigators will take a systematic approach to determining how CES interacts with other circuits in the spinal cord and the brain. In the second half of the study, the Investigators will test combinations of CES with active hand and wrist movements to find ways to enhance physical movement with CES.
These experiments will improve understanding of electrical stimulation in SCI, and may set the table for future treatments to prolong any short-term benefits observed in this study.
Read the detailed description
Roughly 60% of spinal cord injuries occur at the cervical level. Most injuries are anatomically incomplete. Activating spared nerve circuits augments functional recovery of the damaged nervous system. With this goal, the Investigators have developed a novel method of non-invasive cervical electrical stimulation (CES). Preliminary data show that CES triggers afferent sensory or efferent motor nerve roots depending on stimulus intensity, resulting in concurrent activation of multiple muscles on both upper limbs. the Investigators aim to use CES to strengthen residual circuits to hand muscles after SCI. Regaining control over hand function represents the top priority for individuals with cervical SCI.
However, much more work needs to be done to better understand underlying CES mechanisms, its interactions with segmental and supraspinal circuits, and its optimal stimulation parameters for improving neural transmission to the hands. This proposal will address these issues.
Mechanistic experiments: 15 able-bodied volunteers and 15 subjects with motor-incomplete cervical spinal cord injury will undergo systematic combinations of CES with transcranial magnetic stimulation (TMS) or peripheral nerve stimuli at varying intensities, sites, and interstimulus intervals.
Mechanistic hypotheses: Conditioning subthreshold CES pulses will potentiate responses to test pulses of TMS and peripheral nerve F-wave stimulation, will reduce responses to test pulses of peripheral nerve H-reflex stimulation, and will modulate response to test suprathreshold CES pulses in either direction depending on conditioning stimulus interval and intensity. These experiments will elucidate CES circuit interactions at both the segmental and supraspinal levels.
Combined CES-volitional movement experiments: 15 able-bodied volunteers and 15 subjects with motor-incomplete cervical spinal cord injury will undergo systematic combinations of CES with volitional wrist and hand movements at varying intensity and effort level.
Combined CES-volitional movement hypotheses: Conditioning subthreshold CES pulses will facilitate concurrent volitional wrist and hand muscle activation. Suprathreshold CES will transiently inhibit concurrent volitional wrist and hand muscle activation. These experiments will shed light on the clinically relevant possibility of using CES to enhance response to physical exercise therapy.
Completion of the proposed studies will characterize CES circuit timing and distribution, and will demonstrate in principle the potential for CES to enhance physical therapy for wrist and hand muscles. Furthermore, this approach is compatible with other interventions, including drug and cell-based treatments.
- Conditions
- Spinal Cord Injuries
- Being tested
- CES at rest, CES plus active hand or wrist movements
- Keywords
- transcutaneous electric nerve stimulation, transcranial magnetic stimulation
- Medical subject headings
- Spinal Cord Injuries
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 |
|---|---|---|
| All subjects | Experimental | All subjects undergo same full protocol, including CES at rest and CES plus active hand or wrist movements. 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 Responses (Active)
Effect of cervical electrical stimulation (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 one day
Electromyographic Responses to Transcranial Magnetic and Cervical Electrical Stimulation at Rest
Response of the target hand muscle to transcranial magnetic stimulation (delivered at 120% of resting motor threshold) with or without a conditioning cervical electrical stimulator pulse (delivered at 90% of resting motor threshold) timed to arrive at cervical synapses 2 milliseconds after transcranial pulse arrival. Response is expressed as percentage change relative to the response to unconditioned transcranial magnetic stimulation.
Measured: up to one day
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted30 Jan 2018
- Study start22 Aug 2017
- Primary completion30 Apr 2021
- Study completion30 Apr 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.
- Publications (2)Papers the sponsor has linked to this study.
- Other trials for Spinal Cord InjuriesStudies 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
- Basic science
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Enrolment
- 30 participants (actual)
Sponsor and investigators
- Lead sponsor
- Bronx VA Medical Center
- Sponsor type
- US federal agency
- Responsible party
- Principal investigator, Noam Y. Harel, Bronx VA Medical Center
- Investigators
- Noam Y. Harel, MD, PhD, Principal investigator, Bronx VA Medical Center
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT03414424
- Sponsor's protocol ID
- HAR-17-017
- Status last verified
- Nov 2023
- First submitted
- 16 Jan 2018
- Last updated
- 29 Nov 2023
- 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 CFR Part 1.466.
Publications
Wu YK, Levine JM, Wecht JR, Maher MT, LiMonta JM, Saeed S, Santiago TM, Bailey E, Kastuar S, Guber KS, Yung L, Weir JP, Carmel JB, Harel NY. Posteroanterior cervical transcutaneous spinal stimulation targets ventral and dorsal nerve roots. Clin Neurophysiol. 2020 Feb;131(2):451-460. doi: 10.1016/j.clinph.2019.11.056. Epub 2019 Dec 13.
PubMed 31887616Wecht JR, Savage WM, Famodimu GO, Mendez GA, Levine JM, Maher MT, Weir JP, Wecht JM, Carmel JB, Wu YK, Harel NY. Posteroanterior Cervical Transcutaneous Spinal Cord Stimulation: Interactions with Cortical and Peripheral Nerve Stimulation. J Clin Med. 2021 Nov 15;10(22):5304. doi: 10.3390/jcm10225304.
PubMed 34830584
Study at a glance
From the registry record, last updated by the sponsor on 29 Nov 2023. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Non-invasive Cervical Electrical Stimulation for SCI
- ClinicalTrials.gov ID
- NCT03414424
- Acronym / sponsor ID
- HAR-17-017
- Conditions
- Spinal Cord Injuries
- Keywords
- transcutaneous electric nerve stimulation, transcranial magnetic stimulation
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 30 participants (actual)
- Lead sponsor
- Bronx VA Medical CenterUS federal agency
- Study start
- 22 Aug 2017 (actual)
- Primary completion
- 30 Apr 2021 (actual)
- Study completion
- 30 Apr 2021 (actual)
- First posted
- 30 Jan 2018 (actual)
- Results
- Posted 29 Nov 2023
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
Most spinal cord injuries (SCI) are anatomically incomplete - some nerve circuits remain intact, even if the individual cannot feel or control them. Activating spared nerve circuits may improve functional recovery.
With this goal, the Investigators have developed a form of electrical stimulation over the cervical spinal cord that can activate muscles in both hands simultaneously and comfortably. This technique, called cervical electrical stimulation (CES), works at the skin surface - no surgery or other invasive procedures are required.
The long-term goal is to use CES to strengthen residual circuits to hand muscles after SCI. Regaining control over hand function represents the top priority for individuals with cervical SCI.
In the current study, the Investigators first need to better understand how CES works. In the first half of this study, the Investigators will take a systematic approach to determining how CES interacts with other circuits in the spinal cord and the brain. In the second half of the study, the Investigators will test combinations of CES with active hand and wrist movements to find ways to enhance physical movement with CES.
These experiments will improve understanding of electrical stimulation in SCI, and may set the table for future treatments to prolong any short-term benefits observed in this study.
Detailed description
Roughly 60% of spinal cord injuries occur at the cervical level. Most injuries are anatomically incomplete. Activating spared nerve circuits augments functional recovery of the damaged nervous system. With this goal, the Investigators have developed a novel method of non-invasive cervical electrical stimulation (CES). Preliminary data show that CES triggers afferent sensory or efferent motor nerve roots depending on stimulus intensity, resulting in concurrent activation of multiple muscles on both upper limbs. the Investigators aim to use CES to strengthen residual circuits to hand muscles after SCI. Regaining control over hand function represents the top priority for individuals with cervical SCI.
However, much more work needs to be done to better understand underlying CES mechanisms, its interactions with segmental and supraspinal circuits, and its optimal stimulation parameters for improving neural transmission to the hands. This proposal will address these issues.
Mechanistic experiments: 15 able-bodied volunteers and 15 subjects with motor-incomplete cervical spinal cord injury will undergo systematic combinations of CES with transcranial magnetic stimulation (TMS) or peripheral nerve stimuli at varying intensities, sites, and interstimulus intervals.
Mechanistic hypotheses: Conditioning subthreshold CES pulses will potentiate responses to test pulses of TMS and peripheral nerve F-wave stimulation, will reduce responses to test pulses of peripheral nerve H-reflex stimulation, and will modulate response to test suprathreshold CES pulses in either direction depending on conditioning stimulus interval and intensity. These experiments will elucidate CES circuit interactions at both the segmental and supraspinal levels.
Combined CES-volitional movement experiments: 15 able-bodied volunteers and 15 subjects with motor-incomplete cervical spinal cord injury will undergo systematic combinations of CES with volitional wrist and hand movements at varying intensity and effort level.
Combined CES-volitional movement hypotheses: Conditioning subthreshold CES pulses will facilitate concurrent volitional wrist and hand muscle activation. Suprathreshold CES will transiently inhibit concurrent volitional wrist and hand muscle activation. These experiments will shed light on the clinically relevant possibility of using CES to enhance response to physical exercise therapy.
Completion of the proposed studies will characterize CES circuit timing and distribution, and will demonstrate in principle the potential for CES to enhance physical therapy for wrist and hand muscles. Furthermore, this approach is compatible with other interventions, including drug and cell-based treatments.
Study design
- Primary purpose
- Basic science
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Number of arms
- 1
| Arm | Type | Receives |
|---|---|---|
| All subjects | Experimental | Device: CES at rest, Device: CES plus active hand or wrist movementsAll subjects undergo same full protocol, including CES at rest and CES plus active hand or wrist movements. |
Who may qualify
- Ages
- 18 to 75 years
- Sex
- All
- Healthy volunteers
- Accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (5 listed)
- Age between 18 and 75 years;
- Chronic (more than 12 months since injury) incomplete SCI between levels C2-C8.
- Incomplete weakness of left or right hand muscles: score of 2, 3, or 4 (out of 5) on manual muscle testing of finger extension, finger flexion, or finger abduction;
- Detectable F-wave responses of the left or right abductor pollicis brevis muscle to median nerve stimulation.
- US Veteran or non-Veteran
Key exclusion criteria (17 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 | All subjects |
| 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 | All subjects |
Primary outcome
Electromyographic Responses (Active)
Time frame: up to one day
Effect of cervical electrical stimulation (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.
Electromyographic Responses to Transcranial Magnetic and Cervical Electrical Stimulation at Rest
Time frame: up to one day
Response of the target hand muscle to transcranial magnetic stimulation (delivered at 120% of resting motor threshold) with or without a conditioning cervical electrical stimulator pulse (delivered at 90% of resting motor threshold) timed to arrive at cervical synapses 2 milliseconds after transcranial pulse arrival. Response is expressed as percentage change relative to the response to unconditioned transcranial magnetic stimulation.
Results and safety
Loading the posted results from ClinicalTrials.gov…
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 29 Nov 2023.
- Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
- Background: PubMed 31887616Wu YK, Levine JM, Wecht JR, Maher MT, LiMonta JM, Saeed S, Santiago TM, Bailey E, Kastuar S, Guber KS, Yung L, Weir JP, Carmel JB, Harel NY. Posteroanterior cervical transcutaneous spinal stimulation targets ventral and dorsal nerve roots. Clin Neurophysiol. 2020 Feb;131(2):451-460. doi: 10.1016/j.clinph.2019.11.056. Epub 2019 Dec 13.
- Results publication: PubMed 34830584Wecht JR, Savage WM, Famodimu GO, Mendez GA, Levine JM, Maher MT, Weir JP, Wecht JM, Carmel JB, Wu YK, Harel NY. Posteroanterior Cervical Transcutaneous Spinal Cord Stimulation: Interactions with Cortical and Peripheral Nerve Stimulation. J Clin Med. 2021 Nov 15;10(22):5304. doi: 10.3390/jcm10225304.
- 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 CFR Part 1.466.
Related trials for Spinal Cord Injuries
Recruiting
Efficacy of rTMS Treatment After Spinal Cord Injury
Spinal Cord Injuries, Myelopathy
Enrolling by invitation
NeuroSuitUp: Neurorehabilitation Through Synergistic Man-machine Interfaces
Spinal Cord Injuries
Active, not recruitingObservational study
Recovery and Safety After Epidural Spinal Cord Stimulation in People With Spinal Cord Injury
Spinal Cord Injury
RecruitingObservational study
Rare Disease Patient Registry & Natural History Study - Coordination of Rare Diseases at Sanford
Rare Disorders, Undiagnosed Disorders
RecruitingPhase 2
Extracorporeal Shockwave Therapy as an Additional Treatment for Spasticity Secondary to Spinal Cord Injury
Spinal Cord Injury, Spasticity
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
Bronx VA 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 Spinal Cord Injuries, run by Bronx VA Medical Center 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 5 inclusion and 17 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 29 Nov 2023. 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 29 Nov 2023). 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 Responses (Active) (time frame: up to one 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?
On the ClinicalTrials.gov record for NCT03414424, which also lists 2 linked publications.
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 29 Nov 2023.