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Noninvasive Brain Stimulation to Evaluate Neural Plasticity After Stroke

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details.
 
ClinicalTrials.gov Identifier: NCT02465034
Recruitment Status : Suspended (Enrollment and study activities are temporarily suspended due to COVID-19.)
First Posted : June 8, 2015
Last Update Posted : May 14, 2020
Sponsor:
Information provided by (Responsible Party):
Michael Borich, Emory University

Brief Summary:
The purpose of this study is to examine how different areas in the brain interact with each other and how using brain imaging and brain stimulation approaches can influence these interactions.

Condition or disease Intervention/treatment Phase
Cerebrovascular Stroke Device: Transcranial Magnetic Stimulation (Magstim) Device: Traditional Paired Associative Stimulation Device: Median Nerve Stimulation Device: Corticocortical Paired Associative Stimulation Device: Sham Paired Associative Stimulation Not Applicable

Detailed Description:
Subcortical strokes affect small vessels deep in the brain, and typically present with motor hemiparesis. The investigator will assess the effects of Transcranial Magnetic Stimulation (TMS) on motor function and examine how different areas in the human brain interact with each other using brain imaging and brain stimulation. The investigator will also evaluate the capacity for noninvasive stimulation to transiently modify brain activity supporting arm movement.

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Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 75 participants
Allocation: Non-Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Official Title: Noninvasive Brain Stimulation to Evaluate Neural Plasticity After Stroke
Actual Study Start Date : May 2015
Estimated Primary Completion Date : December 2020
Estimated Study Completion Date : December 2020

Arm Intervention/treatment
Active Comparator: Subcortical stroke
Subjects with subcortical stroke in the chronic phase of recovery with mild-moderate impairment of arm function will undergo noninvasive targeting of cortical locations by stereotactic neuronavigation using Transcranial Magnetic Stimulation (TMS), median nerve stimulation and arm motor function assessments. A paired associative stimulation (PAS) protocol using noninvasive stimulation will also be used which will be one of the following, a traditional or a corticocortical or a sham paired associative stimulation protocol. The subjects will also undergo median nerve stimulation.
Device: Transcranial Magnetic Stimulation (Magstim)
Transcranial Magnetic Stimulation (TMS) will be performed using the Magstim BiStim^2 paired pulse stimulator to measure transient cortical excitability. Single pulse transcranial magnetic stimulation applied at low frequencies (not greater than 0.25 Hz) will be used. The may be repeated at multiple study visits. All five study visits will be completed within four weeks of the initial visit.

Device: Traditional Paired Associative Stimulation
Paired associative stimulation (PAS) is a combination of transcranial magnetic stimulation (TMS) and electrical stimulation of the median nerve. 180 paired stimuli are delivered at 0.25Hz for 12 minutes. Median nerve stimuli at 300% of the perceptual threshold will be applied 25ms prior to transcranial magnetic stimulation delivery over the ipsilesional (stroke) or non-dominant (control) cortex. Transcranial Magnetic Stimulation (TMS) will be performed using the Magstim BiStim^2 paired pulse stimulator unit and a bipolar bar electrode will be used for median nerve stimulation. This traditional paired associative stimulation may be repeated at multiple study visits. All five study visits will be completed within four weeks of the initial visit.

Device: Median Nerve Stimulation
Stimulation of the median nerve will be performed using a bipolar bar electrode affixed to palmar aspect of the forearm proximal to the crease of the wrist bilaterally. Stimuli will be delivered 23ms prior to the transcranial magnetic stimulation (TMS) pulse with 0.1ms rectangular pulses at an intensity to evoke a 1mV response in the abductor pollicis brevis (APB) muscle. This may may be repeated at multiple study visits. All five study visits will be completed within four weeks of the initial visit.

Device: Corticocortical Paired Associative Stimulation
Corticocortical Paired associative stimulation (ccPAS) is a combination of transcranial magnetic stimulation (TMS) and electrical stimulation of the median nerve. 180 paired stimuli are delivered at 0.25Hz for 12 minutes. The interstimulus interval will range from 5-15ms depending on site of stimulation.Transcranial Magnetic Stimulation (TMS) will be performed using the Magstim BiStim^2 paired pulse stimulator unit and a bipolar bar electrode will be used for median nerve stimulation. This corticocortical paired associative stimulation may be repeated at multiple study visits. All five study visits will be completed within four weeks of the initial visit.

Device: Sham Paired Associative Stimulation
The sham paired associative stimulation (PAS) is a combination of transcranial magnetic stimulation (TMS) and electrical stimulation of the median nerve. The coil is rotated and separated from the head with a plastic spacer to ensure indirect contact with the head.180 paired stimuli are delivered at 0.25Hz for 12 minutes. Transcranial Magnetic Stimulation (TMS) will be performed using the Magstim BiStim^2 paired pulse stimulator unit and a bipolar bar electrode will be used for median nerve stimulation. This sham paired associative stimulation may be repeated at multiple study visits. All five study visits will be completed within four weeks of the initial visit.

Active Comparator: Healthy Control
Healthy individuals matched for age, gender and handedness with the subcortical stroke group will undergo noninvasive targeting of cortical locations by stereotactic neuronavigation using Transcranial Magnetic Stimulation (TMS), median nerve stimulation and arm motor function assessments. A paired associative stimulation (PAS) protocol using noninvasive stimulation will also be used which will be one of the following, a traditional or a corticocortical or a sham paired associative stimulation protocol.
Device: Transcranial Magnetic Stimulation (Magstim)
Transcranial Magnetic Stimulation (TMS) will be performed using the Magstim BiStim^2 paired pulse stimulator to measure transient cortical excitability. Single pulse transcranial magnetic stimulation applied at low frequencies (not greater than 0.25 Hz) will be used. The may be repeated at multiple study visits. All five study visits will be completed within four weeks of the initial visit.

Device: Traditional Paired Associative Stimulation
Paired associative stimulation (PAS) is a combination of transcranial magnetic stimulation (TMS) and electrical stimulation of the median nerve. 180 paired stimuli are delivered at 0.25Hz for 12 minutes. Median nerve stimuli at 300% of the perceptual threshold will be applied 25ms prior to transcranial magnetic stimulation delivery over the ipsilesional (stroke) or non-dominant (control) cortex. Transcranial Magnetic Stimulation (TMS) will be performed using the Magstim BiStim^2 paired pulse stimulator unit and a bipolar bar electrode will be used for median nerve stimulation. This traditional paired associative stimulation may be repeated at multiple study visits. All five study visits will be completed within four weeks of the initial visit.

Device: Median Nerve Stimulation
Stimulation of the median nerve will be performed using a bipolar bar electrode affixed to palmar aspect of the forearm proximal to the crease of the wrist bilaterally. Stimuli will be delivered 23ms prior to the transcranial magnetic stimulation (TMS) pulse with 0.1ms rectangular pulses at an intensity to evoke a 1mV response in the abductor pollicis brevis (APB) muscle. This may may be repeated at multiple study visits. All five study visits will be completed within four weeks of the initial visit.

Device: Corticocortical Paired Associative Stimulation
Corticocortical Paired associative stimulation (ccPAS) is a combination of transcranial magnetic stimulation (TMS) and electrical stimulation of the median nerve. 180 paired stimuli are delivered at 0.25Hz for 12 minutes. The interstimulus interval will range from 5-15ms depending on site of stimulation.Transcranial Magnetic Stimulation (TMS) will be performed using the Magstim BiStim^2 paired pulse stimulator unit and a bipolar bar electrode will be used for median nerve stimulation. This corticocortical paired associative stimulation may be repeated at multiple study visits. All five study visits will be completed within four weeks of the initial visit.

Device: Sham Paired Associative Stimulation
The sham paired associative stimulation (PAS) is a combination of transcranial magnetic stimulation (TMS) and electrical stimulation of the median nerve. The coil is rotated and separated from the head with a plastic spacer to ensure indirect contact with the head.180 paired stimuli are delivered at 0.25Hz for 12 minutes. Transcranial Magnetic Stimulation (TMS) will be performed using the Magstim BiStim^2 paired pulse stimulator unit and a bipolar bar electrode will be used for median nerve stimulation. This sham paired associative stimulation may be repeated at multiple study visits. All five study visits will be completed within four weeks of the initial visit.




Primary Outcome Measures :
  1. Change in long-term potentiation-like plasticity [ Time Frame: Baseline and post-Paired Associative Stimulation (1min post) ]
    Long-term potentiation-like plasticity will be measured using paired associative stimulation (PAS). PAS consists of repeated peripheral electric stimulation paired with Transcranial Magnetic Stimulation (TMS) applied to the motor cortex at varying interstimulus intervals. Subjects will receive 180 paired stimuli at 0.25Hz for 12 minutes. Impaired long-term potentiation-like plasticity points towards reduced excitatory synaptic connectivity and deficits in sensorimotor integration. Decrease or no change in the amplitudes of motor-evoked potentials (MEPs) indicates impaired long-term potentiation-like plasticity.

  2. Change in electroencephalography recordings [ Time Frame: Baseline and post-Paired Associative Stimulation (5min post) ]
    Electroencephalography data will be recorded using a 64-channel TMS-compatible electrode cap (Easy Cap). Signals will be collected at 2000Hz during pre- and post-transcranial magnetic stimulation epochs (-100ms to 200ms). Fifty suprathreshold (120% AMT) transcranial magnetic stimulation pulses will be applied to motor cortex while the subject is seated quietly with eyes open. This procedure will be conducted bilaterally. Single-channel evoked potentials will be defined as the area under the curve obtained between 10 and 150ms poststimulus. Lower amplitudes indicate decreased cortical activity.

  3. Change in Nine Hole Peg Test completion times [ Time Frame: Baseline and post-Paired Associative Stimulation (10min post) ]
    The Nine Hole Peg Test is administered by asking the subject to take pegs from a container, one by one, and place them into the holes on the board, as quickly as possible. Subjects are asked to then remove the pegs from the holes, one by one, and replace them back into the container. Only the hand being evaluated will perform the test. The total time taken to complete the task is recorded. Scores are based on the time taken to complete the test activity, and is recorded in seconds. The results are expressed as the number of pegs placed per second. Increased number of pegs placed per second is indicative of greater manual dexterity and increased change scores indicate the contribution of paired associative stimulation to hand dexterity.


Secondary Outcome Measures :
  1. Wolf Motor Function Test [ Time Frame: Baseline ]
    The arm function in subjects in the subcortical stroke group will be evaluated by the Wolf Motor Function Test (WMFT). The test consists of timed and functional tasks and has 17 items. It is composed of 3 parts: Time, functional ability and strength and includes 15 function-based tasks and 2 strength based tasks. Items 1-6 involve timed functional tasks, items 7-14 are measures of strength, and the remaining 9 items consist of analyzing movement quality when completing various tasks. The examiner will test the less affected upper extremity followed by the most affected side. Scores are based on time taken to complete each task. The median time to complete all tasks will be be used to evaluate motor function. Larger values indicate greater upper extremity motor dysfunction

  2. Change in Nine Hole Peg Test completion times [ Time Frame: At 30 minutes post-Paired Associative Stimulation, at 60 minutes post-Paired Associative Stimulation ]
    The Nine Hole Peg Test is administered by asking the subject to take pegs from a container, one by one, and place them into the holes on the board, as quickly as possible. Subjects are asked to then remove the pegs from the holes, one by one, and replace them back into the container. Only the hand being evaluated will perform the test. The total time taken to complete the task is recorded. Scores are based on the time taken to complete the test activity, and is recorded in seconds. The results are expressed as the number of pegs placed per second. Increased number of pegs placed per second is indicative of greater manual dexterity and benefits of paired associative stimulation to hand dexterity.

  3. Change in hand-held dynamometry pressure readings [ Time Frame: Baseline and post-Paired Associative Stimulation (10min post) ]
    The uses a hand-held dynamometer to assess grip strength in the arm. Scores are based on force production in kilograms or pounds; kilograms (0-90), pounds (0-200). The arm being tested is not supported by examiner or armrest and the dynamometer is presented vertically and in line with the forearm. The subject is asked to apply as much grip pressure as possible to the dynamometer. The maximum reading on the dynamometer is recorded. Higher pressure scores indicate better muscle strength in the arm following paired associative stimulation.

  4. Change in hand-held dynamometry pressure readings [ Time Frame: At 30 minutes post-Paired Associative Stimulation, at 60 minutes post-Paired Associative Stimulation ]
    The uses a hand-held dynamometer to assess grip strength in the arm. Scores are based on force production in kilograms or pounds; kilograms (0-90), pounds (0-200). The arm being tested is not supported by examiner or armrest and the dynamometer is presented vertically and in line with the forearm. The subject is asked to apply as much grip pressure as possible to the dynamometer. The maximum reading on the dynamometer is recorded. Higher pressure scores indicate better muscle strength in the arm following paired associative stimulation.

  5. Change in long-term potentiation-like plasticity [ Time Frame: At 30 minutes post-Paired Associative Stimulation, at 60 minutes post-Paired Associative Stimulation ]
    Long-term potentiation-like plasticity will be measured using paired associative stimulation (PAS). PAS consists of repeated peripheral electric stimulation paired with Transcranial Magnetic Stimulation (TMS) applied to the motor cortex at varying interstimulus intervals. Subjects will receive 180 paired stimuli at 0.25Hz for 12 minutes. Impaired long-term potentiation-like plasticity points towards reduced excitatory synaptic connectivity and deficits in sensorimotor integration. Decrease or no change in the amplitudes of motor-evoked potentials (MEPs) indicates impaired long-term potentiation-like plasticity.

  6. Change in electroencephalography recordings [ Time Frame: At 30 minutes post-Paired Associative Stimulation, at 60 minutes post-Paired Associative Stimulation ]
    Electroencephalography data will be recorded using a 64-channel TMS-compatible electrode cap (Easy Cap). Signals will be collected at 2000Hz during pre- and post-transcranial magnetic stimulation epochs (-100ms to 200ms). Fifty suprathreshold (120% AMT) transcranial magnetic stimulation pulses will be applied to motor cortex while the subject is seated quietly with eyes open. This procedure will be conducted bilaterally. Single-channel evoked potentials will be defined as the area under the curve obtained between 10 and 150ms poststimulus. Lower amplitudes indicate decreased cortical activity.



Information from the National Library of Medicine

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Ages Eligible for Study:   18 Years to 85 Years   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   Yes
Criteria

Inclusion Criteria:

  1. Age between 18-85 years
  2. Middle cerebral artery stroke
  3. Individuals with a first time stroke that affects the corona radiata and/or internal capsule

Exclusion Criteria:

  1. Age outside the age range of 18-85 years
  2. Signs of dementia (score < 24 on the Montreal Cognitive Assessment)
  3. Aphasia (score < 13 on the Frenchay Aphasia Screen)
  4. History of head trauma
  5. History of a major psychiatric diagnosis
  6. History of a neurodegenerative disorder
  7. History of substance abuse
  8. Contraindications to Transcranial Magnetic Stimulation

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT02465034


Locations
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United States, Georgia
Emory University
Atlanta, Georgia, United States, 30322
Wesley Woods Center
Atlanta, Georgia, United States, 30322
Sponsors and Collaborators
Emory University
Investigators
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Principal Investigator: Michael Borich, DPT, PhD Emory University
Publications automatically indexed to this study by ClinicalTrials.gov Identifier (NCT Number):
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Responsible Party: Michael Borich, Assistant Professor, Emory University
ClinicalTrials.gov Identifier: NCT02465034    
Other Study ID Numbers: IRB00081268
First Posted: June 8, 2015    Key Record Dates
Last Update Posted: May 14, 2020
Last Verified: May 2020
Keywords provided by Michael Borich, Emory University:
Neural plasticity
Noninvasive brain stimulation
Motor cortex
Additional relevant MeSH terms:
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Stroke
Cerebrovascular Disorders
Brain Diseases
Central Nervous System Diseases
Nervous System Diseases
Vascular Diseases
Cardiovascular Diseases