Spinal Cord InjuryNCT02701777
Enhancing STDP After Spinal Cord Injury
A study testing STDP, Training and Multisite-STDP in people with Spinal Cord Injury, run by VA Office of Research and Development at 1 site in United States.
Trial summary
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. Read more about this study
- Who is it for?
- Ages 18 to 85 yearsHealthy volunteers can take part
- Conditions the study is for
- Spinal Cord Injury
- What is being tested?
- STDP, Training and Multisite-STDP
- Type of treatment
- Lifestyle or therapy programme
- Could I receive a placebo?
- Yes, some participants may receive a placebo
- How many people
- 62 participants
- Where
- 1 siteUnited States
- Study dates
- 1 Mar 2016to 30 Oct 2020
- 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 85 years
- All sexes
- Healthy volunteers accepted
- Adult, Older adult
Who may be able to join
- Participants who are unimpaired healthy controls:
- Male and females between ages 18-85 years
- Right handed
- Able to complete precision grips with both hands
- Able to complete full wrist flexion-extension bilaterally
- Able to walk unassisted
Show all 16Show fewer
- Able to complete full ankle flexion-extension bilaterally
- Participants who have had a spinal cord injury:
- Male and females between ages 18-85 years
- SCI ( 6 months of injury)
- Spinal Cord injury at or above L5
- The ability to produce a visible precision grip force with one hand
- Able to perform some small wrist flexion and extension
- The ability to perform a small visible contraction with dorsiflexion and hip flexor muscles
- No subjects will be excluded based on their race, religion, ethnicity, gender or HIV status.
- ASIA A,B,C, or D
Who cannot join
- Exclusion criteria for enrollment For SCI and Healthy Control Subjects (4-8 exclusion for non-invasive brain stimulation only):
- Uncontrolled medical problems including pulmonary, cardiovascular or orthopedic disease
- Any debilitating disease prior to the SCI that caused exercise intolerance
- Premorbid, ongoing major depression or psychosis, altered cognitive status
- History of head injury or stroke
- Metal plate in skull
Show all 11Show fewer
- History of seizures
- Receiving drugs acting primarily on the central nervous system, which lower the seizure threshold (see appendix 2)
- Pregnant females
- Ongoing cord compression or a syrinx in the spinal cord or who suffer from a spinal cord disease such as spinal stenosis, spina bifida, MS, or herniated disk
- Individuals with scalp shrapnel, cochlear implants, or aneurysm clips.
Trial locations and contacts
1 site in 1 country.
United States1 site
Edward Hines Jr. VA Hospital, Hines, IL
Hines, Illinois, 60141-5000
About this study
Official title: Maximizing Spike - Timing Dependent Plasticity After Spinal Cord Injury
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.
Read the detailed description
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.
- Conditions
- Spinal Cord Injury
- Being tested
- STDP, Training, Sham STDP, Multisite-STDP
- Keywords
- spike timing dependant plasticity
- 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.
STDPOther
Also called Paired stimulation
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.
TrainingBehavioural
The participant will be asked to perform exercises using their hands and arms.
Sham STDPOther
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.
Multisite-STDPOther
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.
| Study group | Role | What they receive |
|---|---|---|
| STDP | Active comparator | 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. Receives: Other: STDP |
| STDP + Training | Active comparator | 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. Receives: Other: STDP; Behavioral: Training |
| Sham STDP + Training | Active comparator | 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. Receives: Behavioral: Training; Other: Sham STDP |
| Multisite-STDP + Training | Other | 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. Receives: Behavioral: Training; Other: Multisite-STDP |
What is being measured
The primary outcome is the main question the study is designed to answer.
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.
Measured: 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.
Secondary outcomes (8)
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.
Measured: 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.
Measured: 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.
Measured: 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.
Measured: 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.
Measured: 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.
Measured: 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.
Measured: 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.
Measured: Measured at baseline, after 40 sessions, and follow up (after 9 months) for Multisite-STDP + Training group.
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted8 Mar 2016 (estimated)
- Study start1 Mar 2016
- Primary completion30 Oct 2020
- Study completion30 Oct 2020
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 Spinal Cord InjuryStudies 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
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Single blind
- Who is masked
- Participant
- Enrolment
- 62 participants (actual)
Sponsor and investigators
- Lead sponsor
- VA Office of Research and Development
- Sponsor type
- US federal agency
- Responsible party
- Sponsor
- Investigators
- Martin Oudega, PhD, Principal investigator, Edward Hines Jr. VA Hospital, Hines, IL
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT02701777
- Sponsor's protocol ID
- B1807-R
- Status last verified
- Jul 2022
- First submitted
- 14 Jan 2016
- Last updated
- 21 Jul 2022
- Results posted
- Yes, on ClinicalTrials.gov
- Data monitoring committee
- No
- FDA-regulated drug
- No
- FDA-regulated device
- No
- Individual data sharing
- No
Study at a glance
From the registry record, last updated by the sponsor on 21 Jul 2022. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Maximizing Spike - Timing Dependent Plasticity After Spinal Cord Injury
- ClinicalTrials.gov ID
- NCT02701777
- Acronym / sponsor ID
- B1807-R
- Conditions
- Spinal Cord Injury
- Keywords
- spike timing dependant plasticity
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 62 participants (actual)
- Lead sponsor
- VA Office of Research and DevelopmentUS federal agency
- Study start
- 1 Mar 2016 (actual)
- Primary completion
- 30 Oct 2020 (actual)
- Study completion
- 30 Oct 2020 (actual)
- First posted
- 8 Mar 2016 (estimated)
- Results
- Posted 20 Jan 2021
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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.
Detailed description
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.
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Single blind (participant)
- Number of arms
- 4
| Arm | Type | Receives |
|---|---|---|
| STDP | Active comparator | Other: STDPPaired 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. |
| STDP + Training | Active comparator | Other: STDP, Behavioral: TrainingPaired 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. |
| Sham STDP + Training | Active comparator | Behavioral: Training, Other: Sham STDPSham 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. |
| Multisite-STDP + Training | Other | Behavioral: Training, Other: Multisite-STDPProspective 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. |
Who may qualify
- Ages
- 18 to 85 years
- Sex
- All
- Healthy volunteers
- Accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (16 listed)
- Male and females between ages 18-85 years
- Right handed
- Able to complete precision grips with both hands
- Able to complete full wrist flexion-extension bilaterally
- Able to walk unassisted
Key exclusion criteria (11 listed)
- Exclusion criteria for enrollment For SCI and Healthy Control Subjects (4-8 exclusion for non-invasive brain stimulation only):
- Uncontrolled medical problems including pulmonary, cardiovascular or orthopedic disease
- Any debilitating disease prior to the SCI that caused exercise intolerance
- Premorbid, ongoing major depression or psychosis, altered cognitive status
- History of head injury or stroke
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 |
|---|---|---|
| STDPAlso: Paired stimulationPaired 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, STDP + Training |
| TrainingThe participant will be asked to perform exercises using their hands and arms. | Behavioural | Multisite-STDP + Training, STDP + Training, Sham STDP + Training |
| Sham STDPSham 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. | Other | Sham STDP + Training |
| Multisite-STDPPaired 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. | Other | Multisite-STDP + Training |
Primary outcome
Functional Assessment
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.
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.
8 secondary outcomes
Amplitude of Motor Evoked Potential (MEP)
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
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
Time frame: ISNCSCI was performed at baseline and after 40 sessions of Multisite-STDP+Training.
ISNCSCI-sensory Scores
Time frame: ISNCSCI was performed at baseline and after 40 sessions of Multisite-STDP+Training.
SCI-QOL-ambulation
Time frame: Measured at baseline, after 40 sessions, and follow up (after 9 months) for Multisite-STDP + Training group.
SCI-QOL-self-care
Time frame: Measured at baseline, after 40 sessions, and follow up (after 9 months) for Multisite-STDP + Training group.
SCI-QOL- Bowel Management Difficulties
Time frame: Measured at baseline, after 40 sessions, and follow up (after 9 months) for Multisite-STDP + Training group.
SCI-QOL- Bladder Management Difficulties
Time frame: Measured at baseline, after 40 sessions, and follow up (after 9 months) for Multisite-STDP + Training group.
Results and safety
Loading the posted results from ClinicalTrials.gov…
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 21 Jul 2022.
- Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
- Individual participant dataSharing planned: No
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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.
Martin Oudega, PhD principal investigator
Edward Hines Jr. VA Hospital, Hines, IL
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A study testing STDP, Training and Multisite-STDP in people with Spinal Cord Injury, 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 16 inclusion and 11 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 21 Jul 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 20 Jan 2021). 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?
Functional Assessment (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.). 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 21 Jul 2022.