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| ID | Type | Description | Link |
|---|---|---|---|
| 1R01NS105646-01A1 | U.S. NIH Grant/Contract | View source | |
| A539300 | Other Identifier | UW Madison | |
| SMPH/RADIOLOGY | Other Identifier | UW Madison | |
| Protocol Version 2/1/22 | Other Identifier | UW Madison |
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| Name | Class |
|---|---|
| National Institute of Neurological Disorders and Stroke (NINDS) | NIH |
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The purpose of this research is to determine if functional muscle stimulation, directed by electroencephalogram (EEG) output, can increase the extent of stroke recovery on behavioral measures and induce brain plasticity as measured by functional magnetic resonance imaging (fMRI). Participants will include stroke patients with upper-limb hemiparesis and can expect to be on study for approximately 4 months.
Ongoing research (NCT02098265) suggests that noninvasive EEG driven Brain Computer Interface (BCI) systems hold the potential for facilitating recovery in the chronic phase after stroke by synchronizing central or brain activity with peripheral movements and thereby harnessing brain plasticity.
The specific aims of this study are:
Aim 1: To investigate the efficacy of active FES vs. passive FES, as measured by changes in behavioral measures. The investigators hypothesize that improvements in motor function will be significantly greater using the active FES therapy than the passive FES therapy.
Aim 2: To investigate the relationship between brain functional activation patterns and behavior changes induced by active vs. passive FES intervention. The investigators hypothesize that changes induced by active FES (as measured by brain fMRI and EEG measures) will show greater adaptive brain reorganization changes (i.e. brain changes that correlate with improved outcomes) than that induced by the passive FES.
Aim 3: To investigate the relationship between brain white matter integrity and behavior changes induced by active vs. passive FES intervention. The investigators hypothesize that changes induced by active FES (as measured by brain DTI measures) will show greater adaptive brain reorganization changes (i.e. brain changes that correlate with improved outcomes) than that induced by the passive FES.
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| Label | Type | Description | Intervention Names |
|---|---|---|---|
| Passive FES | Active Comparator | Subjects randomized to this control group will be asked to participate in a passive FES intervention or non-EEG guided muscle stimulation. Participation will include behavioral assessments, functional magnetic resonance imaging, and functional electric stimulation (FES) treatment. |
|
| Active FES | Experimental | Subjects randomized to this experimental group will be asked to complete the active FES intervention which include EEG guided muscle stimulation. Participation will include behavioral assessments, functional magnetic resonance imaging, functional electric stimulation (FES) treatment, and EEG. |
|
| Name | Type | Description | Arm Group Labels | Other Names |
|---|---|---|---|---|
| Functional Electric Stimulation (FES) | Device | FES uses low energy electrical pulses to artificially generate body movements in individuals with muscle paralysis. FES can be used to generate muscle contraction in otherwise paralyzed limbs to restore function. |
| Measure | Description | Time Frame |
|---|---|---|
| Action Research Arm Test Scores | The Action Research Arm Test (ARAT) is designed for evaluation of upper extremity function. This test consists of sections for Grasp, Grip, Pinch and Gross Movements and comprise a total of 19 tests. Each test is scored 0-3 where 0 is 'no movement' and 3 is 'the movement is performed normally'. Each section is scored separately and the scores added for a total possible range of scores from 0-57 where the higher the score, the complete and efficient the movement. Scores will be reported for baseline, mid (~7 weeks), post (~10 weeks), and end of study, up to 4 months. | baseline, 7 weeks, 10 weeks, 4 months |
| Stroke Impact Scale | The Stroke Impact Scale, or SIS, was created to assess changes in impairments, activities and participation following a stroke. Scores on the SIS will provide an index of clinically "meaningful" change representing the change in the patient's mental and physical abilities concurrent with their performance on the verbal fluency and memory tasks. The 4 physical function domains (strength, hand function, activities of daily living (ADL)/instrumental activities of daily living (IADL), and mobility) will be collapsed to a physical function subscale. All domain scores range from 0 to 100 with 100 being the best. | baseline, 7 weeks, 10 weeks, 4 months |
| Measure | Description | Time Frame |
|---|---|---|
| Change in Electroencephalogram (EEG) Response Strength | EEG was recorded in microvolts (µV) from electrodes C4/C3 during periods of left arm imagery and right arm imagery. EEG Response strength is defined as the spectral power in the mu + beta frequency band (8-30 Hz), averaged over the BCI trials. For each participant and time point, a ratio was computed: Ratio = Power_Left Imagery / Power_Right Imagery. |
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Inclusion Criteria:
Exclusion Criteria:
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| Name | Affiliation | Role |
|---|---|---|
| Vivek Prabhakaran, MD, PhD | University of Wisconsin, Madison | Principal Investigator |
| Facility | Status | City | State | ZIP | Country | Contacts |
|---|---|---|---|---|---|---|
| University of Wisconsin | Madison | Wisconsin | 53706 | United States |
| PubMed Identifier | Type | Citation | Retractions |
|---|---|---|---|
| 27695404 | Result | Young BM, Stamm JM, Song J, Remsik AB, Nair VA, Tyler ME, Edwards DF, Caldera K, Sattin JA, Williams JC, Prabhakaran V. Brain-Computer Interface Training after Stroke Affects Patterns of Brain-Behavior Relationships in Corticospinal Motor Fibers. Front Hum Neurosci. 2016 Sep 16;10:457. doi: 10.3389/fnhum.2016.00457. eCollection 2016. | |
| 26157378 | Result | Young BM, Nigogosyan Z, Walton LM, Remsik A, Song J, Nair VA, Tyler ME, Edwards DF, Caldera K, Sattin JA, Williams JC, Prabhakaran V. Dose-response relationships using brain-computer interface technology impact stroke rehabilitation. Front Hum Neurosci. 2015 Jun 23;9:361. doi: 10.3389/fnhum.2015.00361. eCollection 2015. |
| Label | URL |
|---|---|
| Publication resulting from this work. | View source |
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| ID | Title | Description |
|---|---|---|
| FG000 | Passive FES | Subjects randomized to this control group will be asked to participate in a passive FES intervention or non-EEG guided muscle stimulation. Participation will include behavioral assessments, functional magnetic resonance imaging, and functional electric stimulation (FES) treatment. Functional Electric Stimulation (FES): FES uses low energy electrical pulses to artificially generate body movements in individuals with muscle paralysis. FES can be used to generate muscle contraction in otherwise paralyzed limbs to restore function. Behavioral Assessments: These assessments will include measures of upper extremity motor assessments, standard stroke scales, and measures of activities of daily living. Magnetic Resonance Imaging: A functional magnetic resonance image will be collected. |
| FG001 | Active FES | Subjects randomized to this experimental group will be asked to complete the active FES intervention which include EEG guided muscle stimulation. Participation will include behavioral assessments, functional magnetic resonance imaging, functional electric stimulation (FES) treatment, and EEG. Functional Electric Stimulation (FES): FES uses low energy electrical pulses to artificially generate body movements in individuals with muscle paralysis. FES can be used to generate muscle contraction in otherwise paralyzed limbs to restore function. Behavioral Assessments: These assessments will include measures of upper extremity motor assessments, standard stroke scales, and measures of activities of daily living. Magnetic Resonance Imaging: A functional magnetic resonance image will be collected. EEG: EEG electrodes will be attached to the subject's scalp using a standard, commercially available electrode cap. Proper electrode placement is made according to the international 10-20 system, ensuring complete electrode coverage over sensorimotor cortex. |
| Title | Milestones | Reasons Not Completed | |||||||||||||||||||||||||||
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Overall Study |
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| ID | Title | Description |
|---|---|---|
| BG000 | Passive FES | Subjects randomized to this control group will be asked to participate in a passive FES intervention or non-EEG guided muscle stimulation. Participation will include behavioral assessments, functional magnetic resonance imaging, and functional electric stimulation (FES) treatment. |
| BG001 |
| Units | Counts |
|---|---|
| Participants |
|
| Title | Description | Population Description | Parameter Type | Dispersion Type | Unit of Measure | Calculate Percentage | Denominator Units Selected | Denominators | Classes |
|---|---|---|---|---|---|---|---|---|---|
| Age, Continuous | Mean |
| Type | Title | Description | Population Description | Reporting Status | Anticipated Posting Date | Parameter Type | Dispersion Type | Unit of Measure | Calculate Percentage | Time Frame | Units Analyzed | Denominator Units Selected | Arm/Group Information | Denominators | Classes | Analyses | |||
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Primary | Action Research Arm Test Scores | The Action Research Arm Test (ARAT) is designed for evaluation of upper extremity function. This test consists of sections for Grasp, Grip, Pinch and Gross Movements and comprise a total of 19 tests. Each test is scored 0-3 where 0 is 'no movement' and 3 is 'the movement is performed normally'. Each section is scored separately and the scores added for a total possible range of scores from 0-57 where the higher the score, the complete and efficient the movement. Scores will be reported for baseline, mid (~7 weeks), post (~10 weeks), and end of study, up to 4 months. | Some participants did not provide data for all time points. | Posted | Mean | Standard Deviation | score on a scale | baseline, 7 weeks, 10 weeks, 4 months |
|
up to 4 months
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| ID | Title | Description | Deaths (Affected) | Deaths (At Risk) | Serious Events (Affected) | Serious Events (At Risk) | Other Events (Affected) | Other Events (At Risk) |
|---|---|---|---|---|---|---|---|---|
| EG000 | Passive FES | Subjects randomized to this control group will be asked to participate in a passive FES intervention or non-EEG guided muscle stimulation. Participation will include behavioral assessments, functional magnetic resonance imaging, and functional electric stimulation (FES) treatment. |
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| Title | Organization | Phone | Extension | |
|---|---|---|---|---|
| Dr. Vivek Prabhakaran, MD, PhD | UW School of Medicine and Public Health | (608) 265-5269 | vprabhakaran@uwhealth.org |
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| Type | Includes Protocol | Includes SAP | Includes ICF | Document Label | Document Date | Document Uploaded Date | Document File Name |
|---|---|---|---|---|---|---|---|
| Prot_SAP | Yes | Yes | No | Study Protocol and Statistical Analysis Plan | Feb 1, 2022 | Jul 29, 2025 | Prot_SAP_000.pdf |
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| ID | Term |
|---|---|
| D020521 | Stroke |
| D000783 | Aneurysm |
| D002546 | Ischemic Attack, Transient |
| ID | Term |
|---|---|
| D002561 | Cerebrovascular Disorders |
| D001927 | Brain Diseases |
| D002493 | Central Nervous System Diseases |
| D009422 | Nervous System Diseases |
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| ID | Term |
|---|---|
| D009682 | Magnetic Resonance Spectroscopy |
| ID | Term |
|---|---|
| D013057 | Spectrum Analysis |
| D002623 | Chemistry Techniques, Analytical |
| D008919 | Investigative Techniques |
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| Behavioral Assessments | Behavioral | These assessments will include measures of upper extremity motor assessments, standard stroke scales, and measures of activities of daily living. |
|
| Magnetic Resonance Imaging | Other | A functional magnetic resonance image will be collected. |
|
| EEG | Other | EEG electrodes will be attached to the subject's scalp using a standard, commercially available electrode cap. Proper electrode placement is made according to the international 10-20 system, ensuring complete electrode coverage over sensorimotor cortex. |
|
|
| baseline 1, baseline 2, 7 weeks, 10 weeks, 4 months |
| Signal Change in Functional Magnetic Resonance Imaging (MRI) | To compare the percent signal change in the functional MRI activations before and after functional stimulation. | baseline 1, baseline 2, 7 weeks, 10 weeks, 4 months |
| Nine Hole Peg Test (9HPT) | The 9-HPT is a quick and easy to administer tool for screening fine motor problems in participants. It is a timed test in which nine pegs are inserted and removed from nine holes in the pegboard with each hand. Measured at 5 time points over the length of the study. | baseline 1, baseline 2, 7 weeks, 10 weeks, 4 months |
| Motor Activity Log (MAL): Amount of Use | The MAL is a structured interview developed to assess the use of the more affected upper extremity (UE) in real-world daily activities. Assessed at 5 time points over the length of the study. The Amount of Use scoring is as follows (intermediate scores are possible, 0.5 between each whole number):
| baseline 1, baseline 2, 7 weeks, 10 weeks, 4 months |
| Motor Activity Log (MAL): Quality of Movement | The MAL is a structured interview developed to assess the use of the more affected upper extremity (UE) in real-world daily activities. Assessed at 5 time points over the length of the study. The Quality of Movement was scored as follows (intermediate scores 0.5 between whole numbers are possible):
| baseline 1, baseline 2, 7 weeks, 10 weeks, 4 months |
| Change in Modified Ashworth Scale (MAS) | The MAS measures spasticity where 0 is no increase in muscle tone to 4 where affected part is in rigid in flexion or extension. Assessed at 5 time points over the length of the study. | 4 months |
| Hand Grip Strength | Hand Grip Strength will be assessed using a dynamometer. Measured at 5 time points over the length of the study. | baseline 1, baseline 2, 7 weeks, 10 weeks, 4 months |
| Center for Epidemiologic Studies Depression Scale (CES-D) | The CES-D is a self-report scale and includes 20 items that survey mood, somatic complaints, interactions with others, and motor functioning in the past week. Total possible score 0-60, with the higher score indicating more symptoms of depression. Assessed at 5 time points over the length of the study. | 4 months |
| 25964753 | Result | Song J, Nair VA, Young BM, Walton LM, Nigogosyan Z, Remsik A, Tyler ME, Farrar-Edwards D, Caldera KE, Sattin JA, Williams JC, Prabhakaran V. DTI measures track and predict motor function outcomes in stroke rehabilitation utilizing BCI technology. Front Hum Neurosci. 2015 Apr 27;9:195. doi: 10.3389/fnhum.2015.00195. eCollection 2015. |
| 25120466 | Result | Song J, Young BM, Nigogosyan Z, Walton LM, Nair VA, Grogan SW, Tyler ME, Farrar-Edwards D, Caldera KE, Sattin JA, Williams JC, Prabhakaran V. Characterizing relationships of DTI, fMRI, and motor recovery in stroke rehabilitation utilizing brain-computer interface technology. Front Neuroeng. 2014 Jul 29;7:31. doi: 10.3389/fneng.2014.00031. eCollection 2014. |
| 25009491 | Result | Young BM, Nigogosyan Z, Nair VA, Walton LM, Song J, Tyler ME, Edwards DF, Caldera K, Sattin JA, Williams JC, Prabhakaran V. Case report: post-stroke interventional BCI rehabilitation in an individual with preexisting sensorineural disability. Front Neuroeng. 2014 Jun 24;7:18. doi: 10.3389/fneng.2014.00018. eCollection 2014. |
| Publication resulting from this work. | View source |
| Publication resulting from this work. | View source |
| Publication resulting from this work. | View source |
| Publication resulting from this work. | View source |
| Active FES |
Subjects randomized to this experimental group will be asked to complete the active FES intervention which include EEG guided muscle stimulation. Participation will include behavioral assessments, functional magnetic resonance imaging, functional electric stimulation (FES) treatment, and EEG. |
| BG002 | Total | Total of all reporting groups |
| years |
|
| Sex: Female, Male | Count of Participants | Participants |
|
| Ethnicity (NIH/OMB) | Count of Participants | Participants |
|
| Race (NIH/OMB) | Count of Participants | Participants |
|
| Region of Enrollment | Number | participants |
|
| OG001 | Active FES | Subjects randomized to this experimental group will be asked to complete the active FES intervention which include EEG guided muscle stimulation. Participation will include behavioral assessments, functional magnetic resonance imaging, functional electric stimulation (FES) treatment, and EEG. |
|
|
| Primary | Stroke Impact Scale | The Stroke Impact Scale, or SIS, was created to assess changes in impairments, activities and participation following a stroke. Scores on the SIS will provide an index of clinically "meaningful" change representing the change in the patient's mental and physical abilities concurrent with their performance on the verbal fluency and memory tasks. The 4 physical function domains (strength, hand function, activities of daily living (ADL)/instrumental activities of daily living (IADL), and mobility) will be collapsed to a physical function subscale. All domain scores range from 0 to 100 with 100 being the best. | Some participants did not provide data at all timepoints. | Posted | Mean | Standard Deviation | score on a scale | baseline, 7 weeks, 10 weeks, 4 months |
|
|
|
| Secondary | Change in Electroencephalogram (EEG) Response Strength | EEG was recorded in microvolts (µV) from electrodes C4/C3 during periods of left arm imagery and right arm imagery. EEG Response strength is defined as the spectral power in the mu + beta frequency band (8-30 Hz), averaged over the BCI trials. For each participant and time point, a ratio was computed: Ratio = Power_Left Imagery / Power_Right Imagery. | Some participants did not provide data at all time points | Posted | Mean | Standard Deviation | ratio | baseline 1, baseline 2, 7 weeks, 10 weeks, 4 months |
|
|
|
| Secondary | Signal Change in Functional Magnetic Resonance Imaging (MRI) | To compare the percent signal change in the functional MRI activations before and after functional stimulation. | Some participants did not provide data at all time points | Posted | Mean | Standard Deviation | percent signal change | baseline 1, baseline 2, 7 weeks, 10 weeks, 4 months |
|
|
|
| Secondary | Nine Hole Peg Test (9HPT) | The 9-HPT is a quick and easy to administer tool for screening fine motor problems in participants. It is a timed test in which nine pegs are inserted and removed from nine holes in the pegboard with each hand. Measured at 5 time points over the length of the study. | Some participants did not provide data at all time points. | Posted | Mean | Standard Deviation | seconds | baseline 1, baseline 2, 7 weeks, 10 weeks, 4 months |
|
|
|
| Secondary | Motor Activity Log (MAL): Amount of Use | The MAL is a structured interview developed to assess the use of the more affected upper extremity (UE) in real-world daily activities. Assessed at 5 time points over the length of the study. The Amount of Use scoring is as follows (intermediate scores are possible, 0.5 between each whole number):
| Some participants did not provide data at all timepoints. | Posted | Mean | Standard Deviation | score on a scale | baseline 1, baseline 2, 7 weeks, 10 weeks, 4 months |
|
|
|
| Secondary | Motor Activity Log (MAL): Quality of Movement | The MAL is a structured interview developed to assess the use of the more affected upper extremity (UE) in real-world daily activities. Assessed at 5 time points over the length of the study. The Quality of Movement was scored as follows (intermediate scores 0.5 between whole numbers are possible):
| Some participants did not provide data at all timepoints. | Posted | Mean | Standard Deviation | score on a scale | baseline 1, baseline 2, 7 weeks, 10 weeks, 4 months |
|
|
|
| Secondary | Change in Modified Ashworth Scale (MAS) | The MAS measures spasticity where 0 is no increase in muscle tone to 4 where affected part is in rigid in flexion or extension. Assessed at 5 time points over the length of the study. | MAS data were not collected in order to reduce participant burden associated with completing multiple assessments during study visits. The protocol was not amended to reflect this. | Posted | 4 months |
|
|
| Secondary | Hand Grip Strength | Hand Grip Strength will be assessed using a dynamometer. Measured at 5 time points over the length of the study. | Some participants did not provide data at all timepoints. | Posted | Mean | Standard Deviation | kilograms | baseline 1, baseline 2, 7 weeks, 10 weeks, 4 months |
|
|
|
| Secondary | Center for Epidemiologic Studies Depression Scale (CES-D) | The CES-D is a self-report scale and includes 20 items that survey mood, somatic complaints, interactions with others, and motor functioning in the past week. Total possible score 0-60, with the higher score indicating more symptoms of depression. Assessed at 5 time points over the length of the study. | CES-D data were not collected in order to reduce participant burden associated with completing multiple assessments during study visits. The protocol was not amended to reflect this. | Posted | 4 months |
|
|
| 0 |
| 42 |
| 0 |
| 42 |
| 0 |
| 42 |
| EG001 | Active FES | Subjects randomized to this experimental group will be asked to complete the active FES intervention which include EEG guided muscle stimulation. Participation will include behavioral assessments, functional magnetic resonance imaging, functional electric stimulation (FES) treatment, and EEG. | 0 | 42 | 0 | 42 | 0 | 42 |
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| D014652 | Vascular Diseases |
| D002318 | Cardiovascular Diseases |
| D002545 | Brain Ischemia |
| 7 weeks |
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| 10 weeks |
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| 4 months |
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| 7 weeks |
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| 10 weeks |
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| 4 months |
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| Baseline 2 |
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| 7 weeks |
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| 10 weeks |
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| 4 months |
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| Baseline visit 2 |
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| 7 weeks |
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| 10 weeks |
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| 4 months |
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| baseline 2 |
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| 7 weeks |
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| 10 weeks |
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| 4 months |
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| 7 weeks |
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| 10 weeks |
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| 4 months |
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| 7 weeks |
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| 10 weeks |
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| 4 months |
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