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Effects of Paired Associative Nerve Stimulation on Spinal Cord Injury Subjects

Primary Purpose

Spinal Cord Injuries

Status
Recruiting
Phase
Not Applicable
Locations
Taiwan
Study Type
Interventional
Intervention
20 Hz rTMS (Brain)
iTBS rTMS (Brain)
Anode tsDCS (Spinal)
20 Hz current square-wave pulses (Spinal)
iTBS (Spinal)
sham
Sponsored by
Taipei Medical University Hospital
About
Eligibility
Locations
Arms
Outcomes
Full info

About this trial

This is an interventional treatment trial for Spinal Cord Injuries focused on measuring Spinal Cord Injuries, Trans-cranial magnetic stimulation, Trans-spinal direct current stimulation

Eligibility Criteria

20 Years - 65 Years (Adult, Older Adult)All SexesDoes not accept healthy volunteers

Inclusion Criteria:

  1. Age 20 to 65 years incomplete SCI (American Spinal Injury Association Impairment Scale (ASIA) B to D)
  2. Lesion area above the tenth thoracic vertebra (T10)
  3. Injury time more than one year
  4. Without range of motion (ROM) limitation
  5. Medical condition stable

Exclusion Criteria:

  1. Having pacemaker, cochlear implants, metal in the brain or skull, open wound of brain, or history of epilepsy.
  2. Having seizure history
  3. Having other neurological, mental, medical problems affect this study

Sites / Locations

  • Taipei Medical university HospitalRecruiting

Arms of the Study

Arm 1

Arm 2

Arm 3

Arm 4

Arm 5

Arm Type

Experimental

Experimental

Experimental

Experimental

Sham Comparator

Arm Label

rTMS (Brain) + tsES (Spinal)

rTMS (Brain) + tsES (Spinal) or sham stimulation

iTBS rTMS or sham (Brain) + tsES or sham (Spinal)

iTBS rTMS or sham (Brain) + iTBS or sham (Spinal)

sham (no stimulation on brain nor spinal)

Arm Description

First part 20 Hz rTMS (Brain) + Anode tsDCS (Spinal) Brain: Train pulse: 2 sec Inter-train: 28 sec Total time: 1200 sec Spinal: Continuous direct current (DC): 1200 sec Second part iTBS rTMS(Brain) + 2.5-mA tsDCS (Spinal) Brain: Train pulse: 2 sec Inter-train: 8 sec Total time: 200 sec Spinal: Continuous direct current (DC): 600 sec

First part 20 Hz rTMS (Brain) + 20 Hz current square-wave pulses (Spinal) Brain and spinal: Train pulse: 2 sec Inter-train: 28 sec Total time: 1200 sec Second part iTBS rTMS(Brain) + sham 2.5-mA tsDCS (Spinal) Brain: Train pulse: 2 sec Inter-train: 8 sec Total time: 200 sec Spinal: Sham direct current (DC) stimulation

First part Brain: Train pulse: 2 sec Inter-train: 8 sec Total time: 200 sec Spinal: Continuous direct current (DC): 190 sec Second part Sham iTBS rTMS (Brain) + 2.5-mA tsDCS (Spinal) Sham iTBS rTMS Brain: Spinal: Continuous direct current (DC): 600 sec

First part Brain and spinal: Train pulse: 2 sec Inter-train: 8 sec Total time: 200 sec Second part Sham iTBS rTMS (Brain) + Sham 2.5-mA tsDCS (Spinal) Brain: Sham iTBS rTMS Spinal: Sham direct current (DC) stimulation

First part Sham stimulation. No second part

Outcomes

Primary Outcome Measures

Change of Motor evoked potentials (MEP)
Motor evoked potential (MEP) is recorded from tibialis anterior muscles following direct transcranial magnetic stimulation (TMS) of motor cortex. All TMS is delivered with the participant seated upright on the chair. Both passive and active conditions, participants are instructed to relax their one hand in the seated position. TMS is delivered over the motor cortex (M1) using a concave double cone coil (Magstim Co., United Kingdom) attached to a BiStim magnetic stimulator (Magstim Co., United Kingdom). To locate the optimized site, stimuli are delivered over various points around the Cz (approximate 1 cm distance from Cz). The optimal site is the location around the Cz that evoked the greatest MEP amplitude in tibialis anterior muscles. The onset latency and onset to peak amplitude will be assessed.
Change of resting motor threshold (RMT)
Resting motor threshold (RMT) is recorded from tibialis anterior muscles following transcranial magnetic stimulation. TMS is delivered over the motor cortex (M1) using a concave double cone coil (Magstim Co., United Kingdom) attached to a BiStim magnetic stimulator (Magstim Co., United Kingdom). To locate the optimal site, stimuli are delivered over various points around the Cz (the distance approximate 1 cm from Cz) to get the hot spot point. And then measure the RMT using the minimum stimulus intensity that produced a minimal motor evoked response (about 50 micro-volts (µV) in at least 5 of 10 trials) at rest.

Secondary Outcome Measures

Change of Modified Ashworth Scale (MAS)
Modified Ashworth scale (MAS) measures resistance during passive soft-tissue stretching and is used as a simple measure of spasticity. Scoring is recorded as follows: 0: No increase in muscle tone Slight increase in muscle tone, manifested by a catch and release or by minimal resistance at the end of the range of motion when the affected part(s) is moved in flexion or extension 1+: Slight increase in muscle tone, manifested by a catch, followed by minimal resistance throughout the remainder (less than half) of the Range of motion (ROM) More marked increase in muscle tone through most of the ROM, but affected part(s) easily moved Considerable increase in muscle tone, passive movement difficult Affected part(s) rigid in flexion or extension
Change of Lower Extremities Motor Score (LEMS)
The voluntary muscle strength of five key muscles (hip flexors, knee extensors, ankle dorsiflexors, long toe extensors and ankle plantarflexors) of both lower extremities was tested. Each muscle was given a value between 0 and 5 according to the strength of voluntary muscle contraction. Maximum and minimum LEMS were 50 and 0, respectively.
Change of functional Magnetic Resonance Imaging (fMRI)
Our study will use 3 Tesla (T) magnetic resonance imaging[GE DISCOVERY MR750w system (GE Healthcare, Milwaukee, Wisconsin)] for functional magnetic resonance imaging. Resting-state functional MRI image is an echo-planar Image (EPI) technique, using a parameter time of repetition of 2500 milliseconds, time of echo is 30 milliseconds, 43 axial slices, slice thickness is 3 mm, flip angle is 80 degrees, field of view is 192 × 192 mm, and vixen size is 3 × 3 × 3 mm. The EPI scan for 525 seconds. All subjects are asked to close their eyes and supine. Our study uses the fractional amplitude of low-frequency fluctuations analysis to confirm abnormal brain function.
Change of Surface Electromyography (sEMG)
sEMG recordings using pairs of 1 cm-diameter silver/silver chloride recessed sEMG electrodes placed over the muscle bellies 3 cm apart were made from the right and left quadriceps (mainly rectus femoris) and hamstrings. Electrodes were centered on the long axis over muscle bellies for recording during voluntary motor tasks performed by 30 min cycling exercise. The 4 sEMG channels were recorded with a bandwidth of 30 to 500 Hz and a gain of 1,000. Movement sensor and event cue marker outputs were also recorded and, along with the sEMG, were continually digitized at a rate of 2,000 samples/s for the duration of the protocol.

Full Information

First Posted
December 5, 2019
Last Updated
January 27, 2023
Sponsor
Taipei Medical University Hospital
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1. Study Identification

Unique Protocol Identification Number
NCT04194099
Brief Title
Effects of Paired Associative Nerve Stimulation on Spinal Cord Injury Subjects
Official Title
Development and Application of a Novel Neurorehabilitation Technology With Paired Associative Nerve Stimulation in Spinal Cord Injured Subjects
Study Type
Interventional

2. Study Status

Record Verification Date
January 2023
Overall Recruitment Status
Recruiting
Study Start Date
December 9, 2019 (Actual)
Primary Completion Date
September 30, 2023 (Anticipated)
Study Completion Date
December 31, 2023 (Anticipated)

3. Sponsor/Collaborators

Responsible Party, by Official Title
Principal Investigator
Name of the Sponsor
Taipei Medical University Hospital

4. Oversight

Studies a U.S. FDA-regulated Drug Product
No
Studies a U.S. FDA-regulated Device Product
No

5. Study Description

Brief Summary
This study is to investigate the effects of repetitive transcranial magnetic stimulation (rTMS) combined with trans-spinal electrical stimulation (tsES) intervention on cortical excitability, brain structure, motor ability of lower limb in individuals with incomplete spinal cord injury. Twelve participants will be recruited in this study.
Detailed Description
Spinal cord injury (SCI) impairs motor and sensory function and affects numerous body functions and daily activities. Insufficient central nervous system plasticity can result in maladaptive changes that prevent full recovery. It's a challenge to guide this plasticity to optimize the functional outcome for individuals with SCI. Transcranial magnetic stimulation (TMS) and trans-spinal electric stimulation (tsES) may modulate cortical excitability, corticospinal output and spinal circuit. However, few studies investigated the effectiveness of paired nerve stimulation (PNS) on neuroplasticity and functional outcome in persons with SCI. Therefore, this study aim to examine the effects of the combination of these two different non-invasive nerve stimulation with the cycling exercise on the motor cortex and corticospinal circuit excitability as well as functional recovery. Present study clarifies the effects of five different settings of combined with TMS and tsES intervention and then undergo cycling exercise after PNS on spinal cord and cortical excitability in SCI participants. It is expected that this project will successfully establish a new neuromodulation technology to enhance cortical, corticospinal and spinal circuit excitability as well as to improve the outcome of lower-limb function and quality of life in persons with SCI. Therefore, this project can not only publish scientific papers, but also can enhance the neuroplasticity and improve function in persons with SCI.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Spinal Cord Injuries
Keywords
Spinal Cord Injuries, Trans-cranial magnetic stimulation, Trans-spinal direct current stimulation

7. Study Design

Primary Purpose
Treatment
Study Phase
Not Applicable
Interventional Study Model
Parallel Assignment
Masking
Outcomes Assessor
Allocation
Randomized
Enrollment
12 (Anticipated)

8. Arms, Groups, and Interventions

Arm Title
rTMS (Brain) + tsES (Spinal)
Arm Type
Experimental
Arm Description
First part 20 Hz rTMS (Brain) + Anode tsDCS (Spinal) Brain: Train pulse: 2 sec Inter-train: 28 sec Total time: 1200 sec Spinal: Continuous direct current (DC): 1200 sec Second part iTBS rTMS(Brain) + 2.5-mA tsDCS (Spinal) Brain: Train pulse: 2 sec Inter-train: 8 sec Total time: 200 sec Spinal: Continuous direct current (DC): 600 sec
Arm Title
rTMS (Brain) + tsES (Spinal) or sham stimulation
Arm Type
Experimental
Arm Description
First part 20 Hz rTMS (Brain) + 20 Hz current square-wave pulses (Spinal) Brain and spinal: Train pulse: 2 sec Inter-train: 28 sec Total time: 1200 sec Second part iTBS rTMS(Brain) + sham 2.5-mA tsDCS (Spinal) Brain: Train pulse: 2 sec Inter-train: 8 sec Total time: 200 sec Spinal: Sham direct current (DC) stimulation
Arm Title
iTBS rTMS or sham (Brain) + tsES or sham (Spinal)
Arm Type
Experimental
Arm Description
First part Brain: Train pulse: 2 sec Inter-train: 8 sec Total time: 200 sec Spinal: Continuous direct current (DC): 190 sec Second part Sham iTBS rTMS (Brain) + 2.5-mA tsDCS (Spinal) Sham iTBS rTMS Brain: Spinal: Continuous direct current (DC): 600 sec
Arm Title
iTBS rTMS or sham (Brain) + iTBS or sham (Spinal)
Arm Type
Experimental
Arm Description
First part Brain and spinal: Train pulse: 2 sec Inter-train: 8 sec Total time: 200 sec Second part Sham iTBS rTMS (Brain) + Sham 2.5-mA tsDCS (Spinal) Brain: Sham iTBS rTMS Spinal: Sham direct current (DC) stimulation
Arm Title
sham (no stimulation on brain nor spinal)
Arm Type
Sham Comparator
Arm Description
First part Sham stimulation. No second part
Intervention Type
Device
Intervention Name(s)
20 Hz rTMS (Brain)
Intervention Description
Higher frequency (>5 Hz) trains increase cortical excitability.
Intervention Type
Device
Intervention Name(s)
iTBS rTMS (Brain)
Intervention Description
Intermittent theta burst stimulation (iTBS) is a newer rTMS approach.
Intervention Type
Device
Intervention Name(s)
Anode tsDCS (Spinal)
Intervention Description
Anodal tsDCS increased the spinal reflex amplitude, as well as corticospinal excitability.
Intervention Type
Device
Intervention Name(s)
20 Hz current square-wave pulses (Spinal)
Intervention Description
Higher frequency (>5 Hz) of current increase cortical excitability.
Intervention Type
Device
Intervention Name(s)
iTBS (Spinal)
Intervention Description
Intermittent theta-burst stimulation (iTBS) is a newer approach. it may increase corticospinal excitability.
Intervention Type
Device
Intervention Name(s)
sham
Intervention Description
with sham stimulation on brain and spinal.
Primary Outcome Measure Information:
Title
Change of Motor evoked potentials (MEP)
Description
Motor evoked potential (MEP) is recorded from tibialis anterior muscles following direct transcranial magnetic stimulation (TMS) of motor cortex. All TMS is delivered with the participant seated upright on the chair. Both passive and active conditions, participants are instructed to relax their one hand in the seated position. TMS is delivered over the motor cortex (M1) using a concave double cone coil (Magstim Co., United Kingdom) attached to a BiStim magnetic stimulator (Magstim Co., United Kingdom). To locate the optimized site, stimuli are delivered over various points around the Cz (approximate 1 cm distance from Cz). The optimal site is the location around the Cz that evoked the greatest MEP amplitude in tibialis anterior muscles. The onset latency and onset to peak amplitude will be assessed.
Time Frame
Just before the intervention start and immediately after the intervention finished.
Title
Change of resting motor threshold (RMT)
Description
Resting motor threshold (RMT) is recorded from tibialis anterior muscles following transcranial magnetic stimulation. TMS is delivered over the motor cortex (M1) using a concave double cone coil (Magstim Co., United Kingdom) attached to a BiStim magnetic stimulator (Magstim Co., United Kingdom). To locate the optimal site, stimuli are delivered over various points around the Cz (the distance approximate 1 cm from Cz) to get the hot spot point. And then measure the RMT using the minimum stimulus intensity that produced a minimal motor evoked response (about 50 micro-volts (µV) in at least 5 of 10 trials) at rest.
Time Frame
Just before the intervention start and immediately after the intervention finished.
Secondary Outcome Measure Information:
Title
Change of Modified Ashworth Scale (MAS)
Description
Modified Ashworth scale (MAS) measures resistance during passive soft-tissue stretching and is used as a simple measure of spasticity. Scoring is recorded as follows: 0: No increase in muscle tone Slight increase in muscle tone, manifested by a catch and release or by minimal resistance at the end of the range of motion when the affected part(s) is moved in flexion or extension 1+: Slight increase in muscle tone, manifested by a catch, followed by minimal resistance throughout the remainder (less than half) of the Range of motion (ROM) More marked increase in muscle tone through most of the ROM, but affected part(s) easily moved Considerable increase in muscle tone, passive movement difficult Affected part(s) rigid in flexion or extension
Time Frame
Just before the intervention start and immediately after the intervention finished.
Title
Change of Lower Extremities Motor Score (LEMS)
Description
The voluntary muscle strength of five key muscles (hip flexors, knee extensors, ankle dorsiflexors, long toe extensors and ankle plantarflexors) of both lower extremities was tested. Each muscle was given a value between 0 and 5 according to the strength of voluntary muscle contraction. Maximum and minimum LEMS were 50 and 0, respectively.
Time Frame
Just before the intervention start and immediately after the intervention finished.
Title
Change of functional Magnetic Resonance Imaging (fMRI)
Description
Our study will use 3 Tesla (T) magnetic resonance imaging[GE DISCOVERY MR750w system (GE Healthcare, Milwaukee, Wisconsin)] for functional magnetic resonance imaging. Resting-state functional MRI image is an echo-planar Image (EPI) technique, using a parameter time of repetition of 2500 milliseconds, time of echo is 30 milliseconds, 43 axial slices, slice thickness is 3 mm, flip angle is 80 degrees, field of view is 192 × 192 mm, and vixen size is 3 × 3 × 3 mm. The EPI scan for 525 seconds. All subjects are asked to close their eyes and supine. Our study uses the fractional amplitude of low-frequency fluctuations analysis to confirm abnormal brain function.
Time Frame
Immediately after the intervention finished.
Title
Change of Surface Electromyography (sEMG)
Description
sEMG recordings using pairs of 1 cm-diameter silver/silver chloride recessed sEMG electrodes placed over the muscle bellies 3 cm apart were made from the right and left quadriceps (mainly rectus femoris) and hamstrings. Electrodes were centered on the long axis over muscle bellies for recording during voluntary motor tasks performed by 30 min cycling exercise. The 4 sEMG channels were recorded with a bandwidth of 30 to 500 Hz and a gain of 1,000. Movement sensor and event cue marker outputs were also recorded and, along with the sEMG, were continually digitized at a rate of 2,000 samples/s for the duration of the protocol.
Time Frame
Just before the intervention start and immediately after the intervention finished.

10. Eligibility

Sex
All
Minimum Age & Unit of Time
20 Years
Maximum Age & Unit of Time
65 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
Inclusion Criteria: Age 20 to 65 years incomplete SCI (American Spinal Injury Association Impairment Scale (ASIA) B to D) Lesion area above the tenth thoracic vertebra (T10) Injury time more than one year Without range of motion (ROM) limitation Medical condition stable Exclusion Criteria: Having pacemaker, cochlear implants, metal in the brain or skull, open wound of brain, or history of epilepsy. Having seizure history Having other neurological, mental, medical problems affect this study
Central Contact Person:
First Name & Middle Initial & Last Name or Official Title & Degree
Chien-Hung Lai, MD PhD
Phone
886-2-27372181
Ext
3538
Email
chlai@tmu.edu.tw
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Chien-Hung Lai, MD PhD
Organizational Affiliation
Taipei Medical University Hospital
Official's Role
Principal Investigator
Facility Information:
Facility Name
Taipei Medical university Hospital
City
Taipei
Country
Taiwan
Individual Site Status
Recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Chien-Hung Lai

12. IPD Sharing Statement

Plan to Share IPD
No

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Effects of Paired Associative Nerve Stimulation on Spinal Cord Injury Subjects

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