Spinal Cord InjuriesNCT03806023
EMG Triggered Closed-Loop Stimulation for Spinal Cord Injury Individuals
A study testing hand movements (signals from thumb muscle) triggered PNS and TMS in people with Spinal Cord Injuries, run by Bronx VA Medical Center at 1 site in United States.
Trial summary
Most individuals with spinal cord injury (SCI) have residual nerve circuits. The investigators aim to strengthen those circuits to improve motor recovery after injury. To do this, the investigators are attempting to pair electrical and magnetic stimulation with physical training targeted toward the connections between… 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?
- hand movements (signals from thumb muscle) triggered PNS and TMS
- Type of treatment
- Medical device
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 8 participants
- Where
- 1 siteUnited States
- Study dates
- 1 Feb 2018to 28 Feb 2020
- Phase
- Interventional
- Are there results?
- None posted in the registry
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) motor-incomplete SCI between neurological levels C2-C8
- Score of 3 or more (out of 5) on manual muscle testing of finger extension, finger flexion, or finger abduction in left or right hand;
- Detectable F-wave responses of the left or right abductor pollicis brevis (APB) to median nerve stimulation;
- Detectable motor evoked potentials in left or right APB;
- Able to perform thumb-middle finger opposition pinch task with detectable APB EMG muscle activity.
Who cannot join
- Multiple spinal cord lesions;
- History of seizures;
- Ventilator dependence or patent tracheostomy site;
- Use of medications that significantly lower seizure threshold, such as tricyclic antidepressants, amphetamines, neuroleptics, dalfampridine, and bupropion;
- History of stroke, brain tumor, brain abscess, or multiple sclerosis;
- History of moderate or severe head trauma (loss of consciousness for greater than one hour or evidence of brain contusion or hemorrhage or depressed skull fracture on prior imaging);
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- History of implanted 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 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;
- History of suicide attempt;
- Active psychosis;
- Heavy alcohol consumption (greater than 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
The Bronx, New York, 10468
About this study
Most individuals with spinal cord injury (SCI) have residual nerve circuits. The investigators aim to strengthen those circuits to improve motor recovery after injury. To do this, the investigators are attempting to pair electrical and magnetic stimulation with physical training targeted toward the connections between nerve circuits. Past studies by other groups have shown that synapse strength can be improved temporarily after a short period of paired stimulation between the brain (motor cortex) and the peripheral nerves serving target muscles - in other words, "Fire Together, Wire Together".
The brain's intention to move a muscle can be read by recording surface electrical activity over target muscles (electromyography or EMG). In animal models of SCI, scientists have successfully used target muscle EMG to trigger spinal cord electrical stimulation pulses while the animals perform physical exercises. Using the body's own signals to trigger nerve stimulation is called "closed-loop stimulation". This might be an optimal method to coordinate brain and nerve activity, especially with the clinical advantage of being possible to combine with physical exercise training. However, whether EMG-triggered closed loop stimulation has the same amount of effect when applied non-invasively in humans is still unknown.
This proposed study is a proof-of-principle to demonstrate the potential of non-invasive closed-loop stimulation in humans with incomplete cervical SCI. We will test different combinations of triggered and non-triggered electrical and magnetic stimulation, and record the short-term effects on nerve transmission and skilled function of hand muscles. This pilot study will be a foundation for future studies combining EMG-triggered stimulation with long-term physical exercise training.
Read the detailed description
In both animal models and humans with spinal cord injury (SCI), synaptic efficacy between corticospinal axons and spinal motor neurons has improved temporarily after a short period of paired stimulation between motor cortex and spinal or peripheral sites. In a demonstration of closed-loop stimulation in SCI rats, target muscle electromyography (EMG) signals were used to trigger spinal cord electrical stimulation while performing physical retraining. Results showed that EMG-triggered stimulation plus physical retraining led to greater motor recovery than non-triggered stimulation or physical training alone. However, these studies used invasive direct spinal cord stimulation in rodent models. Whether this approach can work non-invasively in humans remains unknown.
Twenty participants (10 able bodied and 10 SCI subjects) will be recruited. Each subject will undergo five different 20-minute interventions. Stimulation will be delivered at the motor cortex via transcranial magnetic stimulation (TMS), the median nerve, or both. Stimulation will occur either while the subject is passively at rest or triggered by reaching endogenous EMG threshold during a pinch task. Outcomes will be measured at baseline and every 20 minutes for one hour after the intervention.
The investigators hypothesize that for at least 20 minutes after stimulation, one session of EMG-triggered stimulation will significantly improve motor evoked potential amplitude, increase cortical silent period duration, and decrease time required to complete a pegboard task compared with one session of passively delivered stimulation. The investigators further hypothesize that EMG triggered median nerve stimulation alone will provide equal or greater benefits as EMG triggered TMS or EMG-triggered paired stimulation.
Hypothesis 1: One session of EMG-triggered stimulation will significantly improve motor evoked potential (MEP) amplitude, increase cortical silent period duration of APB, and decrease time required to complete a manual pegboard task compared with one session of passively delivered stimulation or one session of voluntary contraction alone for at least 20 minutes post-stimulation.
Hypothesis 2: EMG-triggered PNS alone will result in equal or greater effects than EMG triggered TMS or TMS+PNS paired stimulation. This would indicate that EMG triggered PNS might be used as a potential intervention to add during physical training, a setting in which TMS is difficult to apply.
- Conditions
- Spinal Cord Injuries
- Being tested
- hand movements (signals from thumb muscle) triggered PNS and TMS
- 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.
hand movements (signals from thumb muscle) triggered PNS and TMSDevice
PNS, TMS or PNS+TMS will be delivered while the participant performs specific finger 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 PNS and TMS at rest and active hand movements (signals from thumb muscle) triggered PNS and TMS. Receives: Device: hand movements (signals from thumb muscle) triggered PNS and TMS |
What is being measured
The primary outcome is the main question the study is designed to answer.
Change in motor evoked potential (MEP) amplitude of the abductor pollicis brevis (APB) muscle response to single pulses of TMS
Measured: Assessed pre, then 0, 20, 40, and 60 minutes post-intervention.
Hand dexterity
Timed performance on a grooved pegboard task.
Measured: Assessed pre, then 0, 20, 40, and 60 minutes post-intervention.
Secondary outcomes (3)
Grip strength
Strength will be quantified using hand-held wireless dynamometry.
Measured: Assessed pre, then 0, 20, 40, and 60 minutes post-intervention.
Change in the duration of the 'cortical silent period' after TMS stimulation during APB contraction
Measured: Assessed pre, then 0, 20, 40, and 60 minutes post-intervention.
F-wave responses of the APB muscle
Measured: Assessed pre, then 0, 20, 40, and 60 minutes post-intervention.
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted16 Jan 2019
- Study start1 Feb 2018
- Primary completion28 Feb 2020
- Study completion28 Feb 2020
Why it stopped: Funding expired due to grant for new project (NCT03851302)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- 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
- 8 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, James J. Peters VA Medical Center
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT03806023
- Sponsor's protocol ID
- Wu-17-18
- Status last verified
- Oct 2020
- First submitted
- 14 Jan 2019
- Last updated
- 5 Oct 2020
- Results posted
- No
- Data monitoring committee
- No
- FDA-regulated drug
- No
- FDA-regulated device
- Yes
- Individual data sharing
- Yes: A Limited Dataset (LDS) 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.
Study at a glance
From the registry record, last updated by the sponsor on 5 Oct 2020. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- EMG Triggered Closed-Loop Stimulation for Spinal Cord Injury Individuals
- ClinicalTrials.gov ID
- NCT03806023
- Acronym / sponsor ID
- Wu-17-18
- Conditions
- Spinal Cord Injuries
- Keywords
- transcutaneous electric nerve stimulation, transcranial magnetic stimulation
- Study type
- Interventional
- Recruitment status
- TerminatedReason stopped: Funding expired due to grant for new project (NCT03851302)
- Enrolment
- 8 participants (actual)
- Lead sponsor
- Bronx VA Medical CenterUS federal agency
- Study start
- 1 Feb 2018 (actual)
- Primary completion
- 28 Feb 2020 (actual)
- Study completion
- 28 Feb 2020 (actual)
- First posted
- 16 Jan 2019 (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.
Most individuals with spinal cord injury (SCI) have residual nerve circuits. The investigators aim to strengthen those circuits to improve motor recovery after injury. To do this, the investigators are attempting to pair electrical and magnetic stimulation with physical training targeted toward the connections between nerve circuits. Past studies by other groups have shown that synapse strength can be improved temporarily after a short period of paired stimulation between the brain (motor cortex) and the peripheral nerves serving target muscles - in other words, "Fire Together, Wire Together".
The brain's intention to move a muscle can be read by recording surface electrical activity over target muscles (electromyography or EMG). In animal models of SCI, scientists have successfully used target muscle EMG to trigger spinal cord electrical stimulation pulses while the animals perform physical exercises. Using the body's own signals to trigger nerve stimulation is called "closed-loop stimulation". This might be an optimal method to coordinate brain and nerve activity, especially with the clinical advantage of being possible to combine with physical exercise training. However, whether EMG-triggered closed loop stimulation has the same amount of effect when applied non-invasively in humans is still unknown.
This proposed study is a proof-of-principle to demonstrate the potential of non-invasive closed-loop stimulation in humans with incomplete cervical SCI. We will test different combinations of triggered and non-triggered electrical and magnetic stimulation, and record the short-term effects on nerve transmission and skilled function of hand muscles. This pilot study will be a foundation for future studies combining EMG-triggered stimulation with long-term physical exercise training.
Detailed description
In both animal models and humans with spinal cord injury (SCI), synaptic efficacy between corticospinal axons and spinal motor neurons has improved temporarily after a short period of paired stimulation between motor cortex and spinal or peripheral sites. In a demonstration of closed-loop stimulation in SCI rats, target muscle electromyography (EMG) signals were used to trigger spinal cord electrical stimulation while performing physical retraining. Results showed that EMG-triggered stimulation plus physical retraining led to greater motor recovery than non-triggered stimulation or physical training alone. However, these studies used invasive direct spinal cord stimulation in rodent models. Whether this approach can work non-invasively in humans remains unknown.
Twenty participants (10 able bodied and 10 SCI subjects) will be recruited. Each subject will undergo five different 20-minute interventions. Stimulation will be delivered at the motor cortex via transcranial magnetic stimulation (TMS), the median nerve, or both. Stimulation will occur either while the subject is passively at rest or triggered by reaching endogenous EMG threshold during a pinch task. Outcomes will be measured at baseline and every 20 minutes for one hour after the intervention.
The investigators hypothesize that for at least 20 minutes after stimulation, one session of EMG-triggered stimulation will significantly improve motor evoked potential amplitude, increase cortical silent period duration, and decrease time required to complete a pegboard task compared with one session of passively delivered stimulation. The investigators further hypothesize that EMG triggered median nerve stimulation alone will provide equal or greater benefits as EMG triggered TMS or EMG-triggered paired stimulation.
Hypothesis 1: One session of EMG-triggered stimulation will significantly improve motor evoked potential (MEP) amplitude, increase cortical silent period duration of APB, and decrease time required to complete a manual pegboard task compared with one session of passively delivered stimulation or one session of voluntary contraction alone for at least 20 minutes post-stimulation.
Hypothesis 2: EMG-triggered PNS alone will result in equal or greater effects than EMG triggered TMS or TMS+PNS paired stimulation. This would indicate that EMG triggered PNS might be used as a potential intervention to add during physical training, a setting in which TMS is difficult to apply.
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: hand movements (signals from thumb muscle) triggered PNS and TMSAll subjects undergo same full protocol, including PNS and TMS at rest and active hand movements (signals from thumb muscle) triggered PNS and TMS. |
Who may qualify
- Ages
- 18 to 75 years
- Sex
- All
- Healthy volunteers
- Accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (6 listed)
- Age between 18 and 75 years;
- Chronic (more than 12 months since injury) motor-incomplete SCI between neurological levels C2-C8
- Score of 3 or more (out of 5) on manual muscle testing of finger extension, finger flexion, or finger abduction in left or right hand;
- Detectable F-wave responses of the left or right abductor pollicis brevis (APB) to median nerve stimulation;
- Detectable motor evoked potentials in left or right APB;
Key exclusion criteria (16 listed)
- Multiple spinal cord lesions;
- History of seizures;
- Ventilator dependence or patent tracheostomy site;
- Use of medications that significantly lower seizure threshold, such as tricyclic antidepressants, amphetamines, neuroleptics, dalfampridine, and bupropion;
- History of stroke, brain tumor, brain abscess, or multiple sclerosis;
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 |
|---|---|---|
| hand movements (signals from thumb muscle) triggered PNS and TMSPNS, TMS or PNS+TMS will be delivered while the participant performs specific finger tasks at different degrees of effort. This is an experiment designed to detect momentary changes in muscle function. | Device | All subjects |
Primary outcome
Change in motor evoked potential (MEP) amplitude of the abductor pollicis brevis (APB) muscle response to single pulses of TMS
Time frame: Assessed pre, then 0, 20, 40, and 60 minutes post-intervention.
Hand dexterity
Time frame: Assessed pre, then 0, 20, 40, and 60 minutes post-intervention.
Timed performance on a grooved pegboard task.
3 secondary outcomes
Grip strength
Time frame: Assessed pre, then 0, 20, 40, and 60 minutes post-intervention.
Change in the duration of the 'cortical silent period' after TMS stimulation during APB contraction
Time frame: Assessed pre, then 0, 20, 40, and 60 minutes post-intervention.
F-wave responses of the APB muscle
Time frame: Assessed pre, then 0, 20, 40, and 60 minutes post-intervention.
Results and safety
The study was stopped early (reason given: Funding expired due to grant for new project (NCT03851302)). Results are not available in the source record.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 5 Oct 2020.
- Individual participant dataSharing planned: Yes. A Limited Dataset (LDS) 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.
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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 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 hand movements (signals from thumb muscle) triggered PNS and TMS 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 6 inclusion and 16 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: stopped early, as of the sponsor's last update on 5 Oct 2020. 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?
The study was stopped early (reason given: Funding expired due to grant for new project (NCT03851302)). Results are not available in the source record.
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?
Change in motor evoked potential (MEP) amplitude of the abductor pollicis brevis (APB) muscle response to single pulses of TMS (time frame: Assessed pre, then 0, 20, 40, and 60 minutes post-intervention.). 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 5 Oct 2020.