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Enhancing STDP After Spinal Cord Injury

Primary Purpose

Spinal Cord Injury

Status

Completed

Phase

Not Applicable

Locations

United States

Study Type

Interventional

Intervention

STDP

Training

Sham STDP

Multisite-STDP

About this trial

This is an interventional treatment trial for Spinal Cord Injury focused on measuring spike timing dependant plasticity

Eligibility Criteria

18 Years - 85 Years (Adult, Older Adult)All SexesAccepts Healthy Volunteers

Inclusion Criteria:

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
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

Exclusion Criteria:

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
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.

Sites / Locations

Edward Hines Jr. VA Hospital, Hines, IL

Arms of the Study

Arm 1

Arm 2

Arm 3

Arm 4

Arm Type

Active Comparator

Other

Arm Label

STDP

STDP + Training

Sham STDP + Training

Multisite-STDP + Training

Arm Description

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.

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.

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.

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.

Outcomes

Primary Outcome Measures

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.

Secondary Outcome Measures

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.

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.

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.

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.

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.

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.

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.

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.

Full Information

NCT ID

NCT02701777

First Posted

January 14, 2016

Last Updated

July 14, 2022

Sponsor

VA Office of Research and Development

1. Study Identification

Unique Protocol Identification Number

NCT02701777

Brief Title

Enhancing STDP After Spinal Cord Injury

Official Title

Maximizing Spike - Timing Dependent Plasticity After Spinal Cord Injury

Study Type

Interventional

2. Study Status

Record Verification Date

July 2022

Overall Recruitment Status

Completed

Study Start Date

March 1, 2016 (Actual)

Primary Completion Date

October 30, 2020 (Actual)

Study Completion Date

October 30, 2020 (Actual)

3. Sponsor/Collaborators

Responsible Party, by Official Title

Sponsor

Name of the Sponsor

VA Office of Research and Development

4. Oversight

Studies a U.S. FDA-regulated Drug Product

Studies a U.S. FDA-regulated Device Product

Product Manufactured in and Exported from the U.S.

Data Monitoring Committee

5. Study Description

Brief 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. 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.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study

Spinal Cord Injury

Keywords

spike timing dependant plasticity

7. Study Design

Primary Purpose

Treatment

Study Phase

Not Applicable

Interventional Study Model

Parallel Assignment

Masking

Participant

Masking Description

participants will not know if they receive real or sham stimulation

Allocation

Randomized

Enrollment

62 (Actual)

8. Arms, Groups, and Interventions

Arm Title

STDP

Arm Type

Active Comparator

Arm Description

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.

Arm Title

STDP + Training

Arm Type

Active Comparator

Arm Description

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.

Arm Title

Sham STDP + Training

Arm Type

Active Comparator

Arm Description

Arm Title

Multisite-STDP + Training

Arm Type

Other

Arm Description

Intervention Type

Other

Intervention Name(s)

STDP

Other Intervention Name(s)

Paired stimulation

Intervention Description

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.

Intervention Type

Behavioral

Intervention Name(s)

Training

Intervention Description

The participant will be asked to perform exercises using their hands and arms.

Intervention Type

Other

Intervention Name(s)

Sham STDP

Intervention Description

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.

Intervention Type

Other

Intervention Name(s)

Multisite-STDP

Intervention Description

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.

Primary Outcome Measure Information:

Title

Functional Assessment

Description

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.

Secondary Outcome Measure Information:

Title

Amplitude of Motor Evoked Potential (MEP)

Description

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.

Title

Maximum Voluntary Contraction

Description

Time Frame

Title

ISNCSCI-motor Scores

Description

Time Frame

ISNCSCI was performed at baseline and after 40 sessions of Multisite-STDP+Training.

Title

ISNCSCI-sensory Scores

Description

Time Frame

ISNCSCI was performed at baseline and after 40 sessions of Multisite-STDP+Training.

Title

SCI-QOL-ambulation

Description

Time Frame

Measured at baseline, after 40 sessions, and follow up (after 9 months) for Multisite-STDP + Training group.

Title

SCI-QOL-self-care

Description

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.

Title

SCI-QOL- Bowel Management Difficulties

Description

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.

Title

SCI-QOL- Bladder Management Difficulties

Description

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.

10. Eligibility

Sex

All

Minimum Age & Unit of Time

18 Years

Maximum Age & Unit of Time

85 Years

Accepts Healthy Volunteers

Eligibility Criteria

Inclusion Criteria: 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 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 Exclusion Criteria: 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 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.

Overall Study Officials:

First Name & Middle Initial & Last Name & Degree

Martin Oudega, PhD

Organizational Affiliation

Edward Hines Jr. VA Hospital, Hines, IL

Official's Role

Principal Investigator

Facility Information:

Facility Name

Edward Hines Jr. VA Hospital, Hines, IL

City

Hines

State/Province

Illinois

ZIP/Postal Code

60141-5000

Country

United States

12. IPD Sharing Statement

Plan to Share IPD

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Enhancing STDP After Spinal Cord Injury

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