An interventional study of STDP and Training in Spinal Cord Injury, sponsored by VA Office of Research and Development. Completed at 1 site in United States. Open to participants aged 18 Years to 85 Years, including healthy volunteers. Per ClinicalTrials.gov, last updated 2022-07-21.
Sponsored by VA Office of Research and Development · Not applicable, Interventional, and Treatment
The overall goal is to develop new clinical approaches to restore limb function after spinal cord injury (SCI). Corticospinal tract (CST) axons are involved in controlling limb function. Paired pulse induced spike-timing dependent plasticity (STDP) enhances synaptic strength between residual CST axons and spinal motoneurons (SMNs) resulting in temporary improvements in limb function in humans with incomplete SCI. Motor training will be combined with paired-pulse STDP stimulation to further enhance plasticity and behavioral recovery.
To induce STDP with paired pulse, corticospinal volleys evoked by either transcranial magnetic stimulation over the primary motor cortex for upper extremities or electrical stimulation over the thoracic spine for lower extremities arrive at corticospinal-motor neuronal synapses of upper- or lower-limb muscles, 1-2 ms before antidromic potentials were elicited in motor neurons by electrical stimulation of corresponding peripheral nerves.
1,950 studies on the registry are indexed under Spinal Cord Injuries; 507 are open to participants now.
This study's enrollment of 62 is above the median of 24 across 1,567 interventional studies indexed under Spinal Cord Injuries.
Browse Spinal Cord Injuries studies →VA Office of Research and Development is the lead sponsor of 1,733 studies on the registry; 396 are open to participants now.
Of its 206 completed or terminated interventional studies of FDA-regulated products, 180 (87%) have results posted.
Counted across the registry records on this site, refreshed daily.
Participants who are unimpaired healthy controls:
Participants who have had a spinal cord injury:
Exclusion Criteria:
Exclusion criteria for enrollment For SCI and Healthy Control Subjects (4-8 exclusion for non-invasive brain stimulation only):
Paired stimulation will be given to the brain and to a peripheral nerve so that the messages are received at the spinal cord at predetermined time.
Other: STDP
Paired stimulation will be given to the brain and to a peripheral nerve so that the messages are received at the spinal cord at predetermined time. Motor training will follow paired stimulation.
Other: STDP · Behavioral: Training
Sham or fake paired stimulation will be given to the brain and to a peripheral nerve so that the messages are received at the spinal cord at predetermined times. Motor training will follow stimulation.
Behavioral: Training · Other: Sham STDP
Prospective Single Cohort Multisite-Paired stimulation will be given to the brain and to a peripheral nerve so that the messages are received at the spinal cord at predetermined time. Motor training will follow paired stimulation.
Behavioral: Training · Other: Multisite-STDP
Paired stimulation will be given to the brain and to a peripheral nerve so that the messages are received at the spinal cord at predetermined time.
Also known as: Paired stimulation
The participant will be asked to perform exercises using their hands and arms.
Sham or fake paired stimulation will be given to the brain and to a peripheral nerve so that the messages are received at the spinal cord at predetermined times.
Paired stimulation will be given to the brain bilaterally, thoracic spine, and several peripheral nerve so that the messages are received at the spinal cord at predetermined time.
Functional Assessment
The Graded Redefined Assessment of Strength Sensibility and Prehension (GRASSP) assessment is a standardized test of functional abilities of the hand. We measure time required to complete the GRASSP test for upper extremity functional assessment. 10-m walk test is used to measure walking speed for lower extremity functional assessment. The time to complete the task is assessed in seconds for both measurements and normalized as percentage of Baseline. Normalization to baseline allows comparison across two different tasks. For STDP, STDP+Training, and Sham-STDP+Training groups, either GRASSP or 10-m walk test was performed in each participant depending on the targeted muscle. For Multisite-STDP + Training group, both GRASSP and 10-m walk test were performed in each participant and the average of two tests were reported below.
Time frame: Measured at baseline, after 10-20 sessions, and follow up (after 6 months) for STDP, STDP+Training, and Sham-STDP+Training groups . Measured at baseline, after 20 and 40 sessions, and follow up (after 9 months) for Multisite-STDP + Training group.
Amplitude of Motor Evoked Potential (MEP)
We measure amplitude of a motor evoked potential evoked by transcranial magnetic stimulation (TMS) or thoracic spine stimulation. The amplitude of MEP is assessed in millivolts and normalized as percentage of Baseline. Normalization to baseline is necessary to allow comparison across different muscles because the targeted muscle is different for each individual depending on the level of injury.
Time frame: Measured at baseline, after 10-20 sessions, and follow up (after 6 months) for STDP, STDP+Training, and Sham-STDP+Training groups . Measured at baseline and after 20 and 40 sessions for Multisite-STDP + Training group.
Maximum Voluntary Contraction
We measure maximum voluntary contraction (MVC) of muscles recorded by electromyography (EMG) in the targeted muscle(s). Average of muscles was reported for Multisite-STDP + Training group. The maximum voluntary contraction is assessed in millivolts and normalized as percentage of Baseline. Normalization to baseline is needed to allow comparison across different muscles because the targeted muscle is different for each individual depending on the level of injury.
Time frame: Measured at baseline, after 10-20 sessions, and follow up (after 6 months) for STDP, STDP+Training, and Sham-STDP+Training groups . Measured at baseline and after 20 and 40 sessions for Multisite-STDP + Training group.
ISNCSCI-motor Scores
Neurological recovery was measured by the International Standards for Neurological Classification of Spinal Cord Injury (ISNCSCI) exam. Motor part of the exam is completed through the testing of key muscle functions corresponding to 10 myotomes (C5-T1 and L2-S1) for right and left side separately. The strength of each muscle function is graded on a six-point scale ranging from 0 meaning complete paralysis to 5 meaning full strength. The total motor score is sum of all motor scores across 10 myotomes for both sides and therefore ranges from 0-100. Higher scores represent better outcome. We reported the total motor score.
Time frame: ISNCSCI was performed at baseline and after 40 sessions of Multisite-STDP+Training.
ISNCSCI-sensory Scores
Neurological recovery was measured by the International Standards for Neurological Classification of Spinal Cord Injury (ISNCSCI) exam. Sensory part of the exam is completed through the testing of a key point in each of the 28 dermatomes (from C2 to S4-5) on the right and left sides of the body. At each of these key points, two aspects of sensation are examined: light touch and pin prick (sharp-dull discrimination). Appreciation of light touch and pin prick sensation at each of the key points is separately scored on a three-point scale; 0-absent, 1-altered, and 2-normal or intact. Therefore, 56 is the maximum score for both light touch and pin prick and the total sensory score ranges from 0 to 112. Higher scores represent better outcome. We reported the total sensory score.
Time frame: ISNCSCI was performed at baseline and after 40 sessions of Multisite-STDP+Training.
SCI-QOL-ambulation
We used questionnaire to assess changes in quality of life. The name of the questionnaire is Spinal Cord Injury Quality of Life (SCI-QOL) and we used four subdomains: ambulation, self-care, bowel management difficulties, and bladder management difficulties. Scores on all subdomains of SCI-QOL use a standardized T metric, with a mean of 50 and a standard deviation of 10. Ambulation subdomain assesses the ability to engage in walking activities in different locations that vary based on speed, time and condition and the ability to manage stairs under different conditions. Higher scores on Ambulation subdomain represent better outcome.
Time frame: Measured at baseline, after 40 sessions, and follow up (after 9 months) for Multisite-STDP + Training group.
SCI-QOL-self-care
We used questionnaire to assess changes in quality of life. The name of the questionnaire is Spinal Cord Injury Quality of Life (SCI-QOL) and we used four subdomains: ambulation, self-care, bowel management difficulties, and bladder management difficulties. Scores on all subdomains of SCI-QOL use a standardized T metric, with a mean of 50 and a standard deviation of 10. Self-care subdomain assesses an individual's ability to perform daily self-care activities such as eating, dressing, grooming, and bathing. Higher scores on Self-care subdomain represent better outcome.
Time frame: Measured at baseline, after 40 sessions, and follow up (after 9 months) for Multisite-STDP + Training group.
SCI-QOL- Bowel Management Difficulties
We used questionnaire to assess changes in quality of life. The name of the questionnaire is Spinal Cord Injury Quality of Life (SCI-QOL) and we used four subdomains: ambulation, self-care, bowel management difficulties, and bladder management difficulties. Scores on all subdomains of SCI-QOL use a standardized T metric, with a mean of 50 and a standard deviation of 10. Bowel management difficulties subdomain measures a range of difficulties associated with bowel management, including an ability to carry out a bowel program; concerns about incontinence and bowel accidents; concerns about difficulty implementing a bowel program; and the impact of bowel management on everyday living. Higher scores on bowel management difficulties subdomain represent better outcome.
Time frame: Measured at baseline, after 40 sessions, and follow up (after 9 months) for Multisite-STDP + Training group.
SCI-QOL- Bladder Management Difficulties
We used questionnaire to assess changes in quality of life. The name of the questionnaire is Spinal Cord Injury Quality of Life (SCI-QOL) and we used four subdomains: ambulation, self-care, bowel management difficulties, and bladder management difficulties. Scores on all subdomains of SCI-QOL use a standardized T metric, with a mean of 50 and a standard deviation of 10. Bladder management difficulties subdomain measures a range of difficulties associated with bladder management, including ability to carry out a bladder program; worry about bladder accidents; concerns about implementing one's bladder program; and impact on everyday living. Higher scores on bladder management difficulties subdomain represent better outcome.
Time frame: Measured at baseline, after 40 sessions, and follow up (after 9 months) for Multisite-STDP + Training group.
| Milestone | STDP | STDP + Training | Sham STDP + Training | Multisite-STDP + Training |
|---|---|---|---|---|
| Started | 17 | 16 | 16 | 13 |
| Completed | 13 | 13 | 12 | 11 |
| Not completed | 4 | 3 | 4 | 2 |
| Withdrew: Some subjects did not like the stimulation. | 4 | 0 | 0 | 2 |
| Withdrew: Some subjects were unable to commit to the training study. | 0 | 3 | 4 | 0 |
The Graded Redefined Assessment of Strength Sensibility and Prehension (GRASSP) assessment is a standardized test of functional abilities of the hand. We measure time required to complete the GRASSP test for upper extremity functional assessment. 10-m walk test is used to measure walking speed for lower extremity functional assessment. The time to complete the task is assessed in seconds for both measurements and normalized as percentage of Baseline. Normalization to baseline allows comparison across two different tasks. For STDP, STDP+Training, and Sham-STDP+Training groups, either GRASSP or 10-m walk test was performed in each participant depending on the targeted muscle. For Multisite-STDP + Training group, both GRASSP and 10-m walk test were performed in each participant and the average of two tests were reported below.
| percentage of Baseline | STDP | STDP + Training | Sham STDP + Training | Multisite-STDP + Training |
|---|---|---|---|---|
| Baseline | 100 ± 0 | 100 ± 0 | 100 ± 0 | 100 ± 0 |
| After 10 sessions | 80.5 ± 9.1 | 75.6 ± 18.6 | 82.6 ± 20.1 | — |
| After 20 sessions | — | — | — | 62.4 ± 10.9 |
| After 40 sessions | — | — | — | 49.1 ± 10.9 |
| Follow-up | — | 78.4 ± 9.6 | 100.6 ± 10.5 | 48.3 ± 16.5 |
We measure amplitude of a motor evoked potential evoked by transcranial magnetic stimulation (TMS) or thoracic spine stimulation. The amplitude of MEP is assessed in millivolts and normalized as percentage of Baseline. Normalization to baseline is necessary to allow comparison across different muscles because the targeted muscle is different for each individual depending on the level of injury.
| percentage of Baseline | STDP | STDP + Training | Sham STDP + Training | Multisite-STDP + Training |
|---|---|---|---|---|
| Baseline | 100 ± 0 | 100 ± 0 | 100 ± 0 | 100 ± 0 |
| After 10 sessions | 153.2 ± 40.7 | 164.6 ± 64.0 | 99.1 ± 12.4 | — |
| After 20 sessions | — | — | — | 233.2 ± 65.9 |
| After 40 sessions | — | — | — | 368.9 ± 108.9 |
| Follow-up | — | 172 ± 57.7 | 89.0 ± 22.1 | — |
We measure maximum voluntary contraction (MVC) of muscles recorded by electromyography (EMG) in the targeted muscle(s). Average of muscles was reported for Multisite-STDP + Training group. The maximum voluntary contraction is assessed in millivolts and normalized as percentage of Baseline. Normalization to baseline is needed to allow comparison across different muscles because the targeted muscle is different for each individual depending on the level of injury.
| percentage of Baseline | STDP | STDP + Training | Sham STDP + Training | Multisite-STDP + Training |
|---|---|---|---|---|
| Baseline | 100 ± 0 | 100 ± 0 | 100 ± 0 | 100 ± 0 |
| After 10 sessions | 139.4 ± 23.3 | 144.6 ± 50.7 | 100.7 ± 12.3 | — |
| After 20 sessions | — | — | — | 161.0 ± 49.5 |
| After 40 sessions | — | — | — | 193.1 ± 71.0 |
| follow-up | — | 154.5 ± 25.0 | 108.8 ± 7.8 | — |
Neurological recovery was measured by the International Standards for Neurological Classification of Spinal Cord Injury (ISNCSCI) exam. Motor part of the exam is completed through the testing of key muscle functions corresponding to 10 myotomes (C5-T1 and L2-S1) for right and left side separately. The strength of each muscle function is graded on a six-point scale ranging from 0 meaning complete paralysis to 5 meaning full strength. The total motor score is sum of all motor scores across 10 myotomes for both sides and therefore ranges from 0-100. Higher scores represent better outcome. We reported the total motor score.
| scores on a scale | Multisite-STDP + Training |
|---|---|
| Baseline | 59.4 ± 23.7 |
| After 40 sessions | 68.9 ± 20.2 |
Neurological recovery was measured by the International Standards for Neurological Classification of Spinal Cord Injury (ISNCSCI) exam. Sensory part of the exam is completed through the testing of a key point in each of the 28 dermatomes (from C2 to S4-5) on the right and left sides of the body. At each of these key points, two aspects of sensation are examined: light touch and pin prick (sharp-dull discrimination). Appreciation of light touch and pin prick sensation at each of the key points is separately scored on a three-point scale; 0-absent, 1-altered, and 2-normal or intact. Therefore, 56 is the maximum score for both light touch and pin prick and the total sensory score ranges from 0 to 112. Higher scores represent better outcome. We reported the total sensory score.
| scores on a scale | Multisite-STDP + Training |
|---|---|
| Baseline | 99.0 ± 34.6 |
| After 40 sessions | 119.9 ± 38.4 |
We used questionnaire to assess changes in quality of life. The name of the questionnaire is Spinal Cord Injury Quality of Life (SCI-QOL) and we used four subdomains: ambulation, self-care, bowel management difficulties, and bladder management difficulties. Scores on all subdomains of SCI-QOL use a standardized T metric, with a mean of 50 and a standard deviation of 10. Ambulation subdomain assesses the ability to engage in walking activities in different locations that vary based on speed, time and condition and the ability to manage stairs under different conditions. Higher scores on Ambulation subdomain represent better outcome.
| T-scores | Multisite-STDP + Training |
|---|---|
| Baseline | 53.7 ± 9.4 |
| After 40 sessions | 57.1 ± 7.9 |
| Follow-up | 61.4 ± 5.3 |
We used questionnaire to assess changes in quality of life. The name of the questionnaire is Spinal Cord Injury Quality of Life (SCI-QOL) and we used four subdomains: ambulation, self-care, bowel management difficulties, and bladder management difficulties. Scores on all subdomains of SCI-QOL use a standardized T metric, with a mean of 50 and a standard deviation of 10. Self-care subdomain assesses an individual's ability to perform daily self-care activities such as eating, dressing, grooming, and bathing. Higher scores on Self-care subdomain represent better outcome.
| T-scores | Multisite-STDP + Training |
|---|---|
| Baseline | 45.9 ± 7.8 |
| After 40 sessions | 47.5 ± 8.0 |
| Follow-up | 48.5 ± 3.6 |
We used questionnaire to assess changes in quality of life. The name of the questionnaire is Spinal Cord Injury Quality of Life (SCI-QOL) and we used four subdomains: ambulation, self-care, bowel management difficulties, and bladder management difficulties. Scores on all subdomains of SCI-QOL use a standardized T metric, with a mean of 50 and a standard deviation of 10. Bowel management difficulties subdomain measures a range of difficulties associated with bowel management, including an ability to carry out a bowel program; concerns about incontinence and bowel accidents; concerns about difficulty implementing a bowel program; and the impact of bowel management on everyday living. Higher scores on bowel management difficulties subdomain represent better outcome.
| T-scores | Multisite-STDP + Training |
|---|---|
| Baseline | 48.2 ± 10.6 |
| After 40 sessions | 51.8 ± 10.7 |
| Follow-up | 45.4 ± 7.3 |
We used questionnaire to assess changes in quality of life. The name of the questionnaire is Spinal Cord Injury Quality of Life (SCI-QOL) and we used four subdomains: ambulation, self-care, bowel management difficulties, and bladder management difficulties. Scores on all subdomains of SCI-QOL use a standardized T metric, with a mean of 50 and a standard deviation of 10. Bladder management difficulties subdomain measures a range of difficulties associated with bladder management, including ability to carry out a bladder program; worry about bladder accidents; concerns about implementing one's bladder program; and impact on everyday living. Higher scores on bladder management difficulties subdomain represent better outcome.
| T-scores | Multisite-STDP + Training |
|---|---|
| Baseline | 41.0 ± 9.5 |
| After 40 sessions | 46.7 ± 7.6 |
| Follow-up | 40.9 ± 7.6 |
Collected over The adverse event data is collected from baseline to completion of study visits, an average of 2~3 weeks for Arms 1-3. The longer experiment, Arm 4, involves ~50 visits (40 sessions + baseline, post 20, post 40, and follow-up assessments). This gives a total of 10~15 weeks.. Non-serious events are listed at a 0% frequency threshold.
| Group | Deaths | Serious | Other |
|---|---|---|---|
| STDP | 0/17 (0%) | 0/17 (0%) | 0/17 (0%) |
| STDP + Training | 0/16 (0%) | 0/16 (0%) | 0/16 (0%) |
| Sham STDP + Training | 0/16 (0%) | 0/16 (0%) | 0/16 (0%) |
| Multisite-STDP + Training | 0/13 (0%) | 0/13 (0%) | 0/13 (0%) |
| Age, Categorical(Participants) | STDP | STDP + Training | Sham STDP + Training | Multisite-STDP + Training | Total |
|---|---|---|---|---|---|
| <=18 years | 0 | 0 | 0 | 0 | 0 |
| Between 18 and 65 years | 12 | 11 | 12 | 8 | 43 |
| >=65 years | 1 | 2 | 0 | 3 | 6 |
| Age, Continuous(years) | STDP | STDP + Training | Sham STDP + Training | Multisite-STDP + Training | Total |
|---|---|---|---|---|---|
| Mean | 45.1 (21 to 71) | 45.6 (23 to 82) | 41.8 (22 to 59) | 48.2 (21 to 84) | 45 (21 to 84) |
| Sex: Female, Male(Participants) | STDP | STDP + Training | Sham STDP + Training | Multisite-STDP + Training | Total |
|---|---|---|---|---|---|
| Female | 4 | 4 | 1 | 5 | 14 |
| Male | 9 | 9 | 11 | 6 | 35 |
| Ethnicity (NIH/OMB)(Participants) | STDP | STDP + Training | Sham STDP + Training | Multisite-STDP + Training | Total |
|---|---|---|---|---|---|
| Hispanic or Latino | 6 | 8 | 6 | 2 | 22 |
| Not Hispanic or Latino | 7 | 5 | 6 | 9 | 27 |
| Unknown or Not Reported | 0 | 0 | 0 | 0 | 0 |
| Race (NIH/OMB)(Participants) | STDP | STDP + Training | Sham STDP + Training | Multisite-STDP + Training | Total |
|---|---|---|---|---|---|
| American Indian or Alaska Native | 0 | 0 | 0 | 0 | 0 |
| Asian | 0 | 0 | 0 | 0 | 0 |
| Native Hawaiian or Other Pacific Islander | 0 | 3 | 3 | 0 | 6 |
| Black or African American | 3 | 0 | 5 | 2 | 10 |
| White | 5 | 5 | 0 | 8 | 18 |
| More than one race | 5 | 5 | 4 | 1 | 15 |
| Unknown or Not Reported | 0 | 0 | 0 | 0 | 0 |
| Region of Enrollment(Participants) | STDP | STDP + Training | Sham STDP + Training | Multisite-STDP + Training | Total |
|---|---|---|---|---|---|
| United States | 13 | 13 | 12 | 11 | 49 |
| Time post injury(years) | STDP | STDP + Training | Sham STDP + Training | Multisite-STDP + Training | Total |
|---|---|---|---|---|---|
| Mean | 7.1 ± 5.4 | 12.7 ± 12.5 | 9.1 ± 6.1 | 8.9 ± 10.6 | 9.5 ± 9.1 |
Documents are hosted by the registry — open the source record to download them.
Plan to share: No
This study is completed, as verified in Jul 2022. You cannot join it, but the record below documents what was studied.
Get an email when the registry record changes — status, dates, results — or when someone posts here.
Sign in to followQuestions and observations about this study, from anyone following it. Not medical advice, and not a channel to the study team — their contact details are on the registry record.
Sign in to join the discussion. Reading takes no account; posting does. You choose a display name, and a pseudonym is the default.
Nothing here yet. If you are running this trial, taking part in it, or weighing whether to, this is the place to say so.
VA Office of Research and Development