StrokeNCT02544503
Customized Cortical Stimulation Therapy in the Rehabilitation of Stroke Patients
A study testing Single-pulse Transcranial Magnetic Stimulation (TMS), Paired-pulse Transcranial Magnetic Stimulation (ppTMS) and Low-frequency Repetitive Transcranial Magnetic Stimulation (rTMS) in people with Stroke, run by Emory University at 3 sites in United States.
Trial summary
The purpose of this study is to identify and establish how the area of the brain that controls motor function (motor cortex) of the non-affected hemisphere after stroke might serve as a new target for therapeutic interventions to improve motor performance after stroke. Read more about this study
- Who is it for?
- Ages 40 to 80 yearsHealthy volunteers can take part
- Conditions the study is for
- Stroke
- What is being tested?
- Single-pulse Transcranial Magnetic Stimulation (TMS), Paired-pulse Transcranial Magnetic Stimulation (ppTMS) and Low-frequency Repetitive Transcranial Magnetic Stimulation (rTMS)
- Type of treatment
- Medical device
- Could I receive a placebo?
- Yes, some participants may receive a placebo
- How many people
- 100 participants
- Where
- 3 sitesUnited States
- Study dates
- 5 Nov 2015to 4 Feb 2021
- 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 40 to 80 years
- All sexes
- Healthy volunteers accepted
- Adult, Older adult
Who may be able to join
- The ability to provide informed consent
- Ages 40 to 80 years old
- Male or female
- Additional Inclusion Criteria for Stroke Patients:
- One cerebral ischemic infarction less than 1 month affecting the primary motor output system of the hand at a cortical (M1) level as defined by magnetic resonance imaging (MRI) of the brain
- Paresis of the hand for more than 3 days after their cerebral infarction
Show all 10Show fewer
- Additional Inclusion Criteria for Healthy Subjects:
- Normal MRI of the brain
- Normal neuropsychological testing
- Normal neurological examination
Who cannot join
- Neurological disorders other than stroke
- Aphasia that prevents following instructions or inability to communicate effectively with the study team
- Dementia
- Moderate or severe depression
- Contraindication to transcranial magnetic stimulation (TMS) and/or MRI
- Use of central nervous system (CNS) active drugs that block plasticity
Show all 10Show fewer
- Neurological Disease
- Psychiatric Disease
- Use of CNS active drugs
- Contraindication to transcranial magnetic stimulation (TMS) and/or MRI
Trial locations and contacts
3 sites in 1 country.
United States3 sites
Center for Rehabilitation Medicine
Atlanta, Georgia, 30322
Emory University Hospital
Atlanta, Georgia, 30322
Emory University School of Medicine
Atlanta, Georgia, 30322
About this study
The purpose of this study is to identify and establish how the area of the brain that controls motor function (motor cortex) of the non-affected hemisphere after stroke might serve as a new target for therapeutic interventions to improve motor performance after stroke.
Read the detailed description
It is well known that the motor area of one hemisphere of the brain (motor cortex) controls the movement of the opposite side of the body but the role of the motor cortex in the hemisphere spared by stroke (contralesional motor cortex) in motor performance during post stroke recovery is still unclear. It is also not clear whether the motor cortex of both hemispheres of the brain are involved, as movement becomes more complicated. Currently the role of the motor cortex on the same side of the body (referred to as ipsilateral motor cortex) in hand performance remains controversial. In most patients with stroke, only one side of the brain is affected by the stroke (affected hemisphere) resulting in weakness of half of the body opposite to the side of the stroke. Over the recent years, research has discovered that the side of the brain, that is spared by the stroke (non-affected hemisphere) may support recovery after stroke. However, there is also a question whether the non-affected hemisphere may interfere with the process of recovery. It is currently not known what factors influence the activity of non-affected hemisphere to either support or interfere with the recovery of stroke. A better understanding of those events is critical to development of optimal therapeutic strategies. For example, non-invasive stimulation of specific areas of the non-affected hemisphere may help to improve functional recovery following stroke. The objectives of this study are to define the factors that influence the activity in the non-affected hemisphere to either support or interfere with the recovery after stroke. The researchers will study the area of the brain that controls movements of the non-affected hemisphere as it relates to motor function post-stroke.
Transcranial magnetic stimulation (TMS) is a device that allows non-invasive stimulation of the brain. When the brain is stimulated repetitively at a very low rate and low intensity for about 15 minutes, the stimulated brain area becomes less active. This effect lasts 10 minutes and is called a "transient artificial lesion" as it mimics the effects of transiently interfering with the function of the stimulated brain area. The study includes experiments that first identify the extent of stroke and brain areas involved in a motor task using functional MRI of the brain and TMS. The researchers will then determine the functional role of the contralesional motor cortex by studying the effect of low frequency and high frequency repetitive transcranial magnetic stimulation (rTMS) of primary motor cortex (M1) on interhemispheric inhibition (IHI) (resting and active) and motor cortex excitability (short interval intracortical excitability and corticospinal excitability) and behavior. The researchers will thereby also identify rTMS protocols that enhance motor performance in stroke patients.
In this study the researchers will conduct experiments using repetitive TMS to downregulate the activity of the motor area and measures its effect on activity of motor cortex of both hemispheres. In addition to enrolling participants who have had a stroke, the researchers will enroll healthy participants as this collected data will provide normative values for task related changes in M1s and their interactions - a prerequisite to studying abnormalities in stroke patients during motor recovery. The measurements and interventions will occur at two time points in all participants with stroke (1 and 6 months post-stroke). The data will be compared to the results of healthy age matched controls, assessed at a single time point.
- Conditions
- Stroke
- Being tested
- Single-pulse Transcranial Magnetic Stimulation (TMS), Paired-pulse Transcranial Magnetic Stimulation (ppTMS), Low-frequency Repetitive Transcranial Magnetic Stimulation (rTMS), Sham Motor Cortex Stimulation
- Keywords
- Subacute stroke, Chronic stroke
- Medical subject headings
- Stroke
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Single-pulse Transcranial Magnetic Stimulation (TMS)Device
Single-pulse Transcranial Magnetic Stimulation (TMS) is a brief magnetic pulse that is applied through a coil to the section of the head that overlays the motor cortex of the brain. Subjects will be comfortably seated in a dental chair surrounded by a frame that carries a coil holder to assist with the application of TMS to the brain. Single-pulse transcranial magnetic stimulation (TMS) will be administered at study visits.
Paired-pulse Transcranial Magnetic Stimulation (ppTMS)Device
Paired-pulse Transcranial Magnetic Stimulation (ppTMS) is two brief sequential magnetic pulses that are applied through a coil to the section of the head that overlays the motor cortex of the brain. Subjects will be comfortably seated in a dental chair surrounded by a frame that carries a coil holder to assist with the application of TMS to the brain. Paired-pulse transcranial magnetic stimulation (ppTMS) will be administered at study visits.
Low-frequency Repetitive Transcranial Magnetic Stimulation (rTMS)Device
Low-frequency Repetitive Transcranial Magnetic Stimulation (rTMS) is a sequence of brief magnetic pulses that are applied at 0.1 Hz frequency at low intensity through an air-cooled coil to the section of the head that overlays the motor cortex of the brain. Subjects will be comfortably seated in a dental chair surrounded by a frame that carries a coil holder to assist with the application of TMS to the brain. Low-frequency repetitive transcranial magnetic stimulation (rTMS) will be administered at study visits.
Sham Motor Cortex StimulationDevice
Sham motor cortex stimulation will be applied at study visits.
| Study group | Role | What they receive |
|---|---|---|
| Stroke Patients | Experimental | Subjects will undergo single pulse transcranial magnetic stimulation (TMS), paired pulse transcranial stimulation (ppTMS), and low frequency repetitive transcranial magnetic stimulation (rTMS) at one month and six months post stroke. Receives: Device: Single-pulse Transcranial Magnetic Stimulation (TMS); Device: Paired-pulse Transcranial Magnetic Stimulation (ppTMS); Device: Low-frequency Repetitive Transcranial Magnetic Stimulation (rTMS); Device: Sham Motor Cortex Stimulation |
| Healthy Controls | Active comparator | Subjects will undergo single pulse transcranial magnetic stimulation (TMS), paired pulse transcranial stimulation (ppTMS), and low frequency repetitive transcranial magnetic stimulation (rTMS) at one month and six months. Receives: Device: Single-pulse Transcranial Magnetic Stimulation (TMS); Device: Paired-pulse Transcranial Magnetic Stimulation (ppTMS); Device: Low-frequency Repetitive Transcranial Magnetic Stimulation (rTMS); Device: Sham Motor Cortex Stimulation |
What is being measured
The primary outcome is the main question the study is designed to answer.
Motor Function Assessed by the Jebsen Test
The Jebsen Test assesses weighted and non-weighted hand function among participants who have had a stroke. Subjects are assessed through writing, turning over 3 by 5 inch cards, picking up small common objects, simulated feeding, stacking checkers, picking up large objects, and picking up large heavy objects. Patients are required to perform all of the subtests with both the right and left hands. Time to complete each task is recorded and normalized to healthy age and sex matched control subjects. The score ranges from 0 to 1 with 0 being normal.
Measured: 1 month post-stroke (subacute stroke), 6 months post-stroke (chronic stroke)
Mean Motor Evoked Potential (MEP) Amplitudes Assessed by Stimulus Response Curve (SRC) of the Contralesional M1
Change in mean motor evoked potential (MEP) amplitudes at each stimulus intensity will be calculated. The sum of these means is calculated as the area under the curve.
Measured: 1 month post-stroke (subacute stroke) or single study visit for healthy controls, 6 months post-stroke (chronic stroke)
Presence of MEP in Response to TMS of the Ipsilesional M1
The presence of motor evoked potential (MEP) in response to maximum TMS applied to ipsilesional M1 was determined in participants with stroke.
Measured: 1 month post-stroke (subacute stroke), 6 months post-stroke (chronic stroke)
Lesion Volume
Normalized stroke lesion volume was determined at the one-month time point using structural MRI of the brain.
Measured: 1 month post-stroke (subacute stroke)
Corticospinal Tract (CST) Lesion
Corticospinal tract (CST) lesion load will be determined at the one-month time point using structural MRI of the brain. The lesion size is expressed as percentage of the entire CST.
Measured: 1 month post-stroke (subacute stroke)
Secondary outcomes (7)
Motor Function Assessed by Time to Complete the Wolf Motor Function Test (WMFT)
Upper extremity motor ability among participants who had a stroke was evaluated with the Wolf Motor Function Test (WMFT). The test consists of 17 items (6 joint-segment movements, 9 integrative functional movements and 2 strength items). The items are rated on a 6-point functional ability scale (FAS) where 0 is "no attempt is made to use the more affected arm and 5 is a normal appearance of movement execution. The time taken to complete each task will be recorded up to 120 seconds. The mean time to complete all tasks will be used to evaluate motor ability.
Measured: 1 month post-stroke (subacute stroke), 6 months post-stroke (chronic stroke)
Motor Function Assessed by Grip Strength During the Wolf Motor Function Test (WMFT)
During the grip strength assessment of the WMFT, participants grip a dynamometer with as much strength as possible. There are three trials of gripping with a minute rest interval between trials. The mean kilograms of strength exerted during the three trials is calculated.
Measured: 1 month post-stroke (subacute stroke), 6 months post-stroke (chronic stroke)
Use of Paretic Arm Assessed by the Motor Activity Log (MAL)
In stroke patients, the everyday use of the paretic (the more affected) arm will be measured using the Motor Activity Log (MAL). The MAL is a subjective measure of semi- structured interview to examine a) how much and b) how well the subject uses their more-affected arm outside of the laboratory setting. Total scores range from 0 (no use of the more-affected arm) to 5 (use is as good as before stroke).
Measured: 1 month post-stroke (subacute stroke), 6 months post-stroke (chronic stroke)
CST Subpathway Originating in M1 Lesion Load
CST sub M1 lesion volume will be determined at the one- month time point using structural MRI of the brain. The lesion load is expressed as percentage of the entire CST.
Measured: 1 month post-stroke (subacute stroke)
Primary Motor Cortex (M1) Activity, Assessed by Functional Magnetic Resonance Imaging (fMRI)
Functional Magnetic Resonance Imaging (fMRI) will be used to determine hand movement related activity in the motor cortex of the brain in all subjects. Blood oxygenation level dependent (BOLD) response during execution of the motor task will be compared to rest. The subacute stroke and chronic stroke time points are compared to single study visit of healthy controls.
Measured: 1 month post-stroke (subacute stroke) or single study visit for healthy controls, 6 months post-stroke (chronic stroke)
Short Interval Cortical Inhibition (SICI) Measured by Repeated Transcranial Magnetic Stimulation (rTMS)
SICI in the contralesional M1 will be measured using paired pulse TMS at an interstimulus interval (ISI) of 2 milliseconds (ms). Cortical stimulation intensity was delivered at 60% and 80% of the motor threshold (MT). SICI is expressed as the ratio between the mean MEP amplitude in response to a single TMS and the mean MEP amplitude in response to a paired pulse TMS. A ratio of 1 means no inhibition, a ratio smaller than 1 means inhibition, and a ratio greater than 1 means facilitation.
Measured: 1 month post-stroke (subacute stroke) or single study visit for healthy controls, 6 months post-stroke (chronic stroke)
Peak Velocity During Wrist Extension Movement
Stroke patients are asked to rapidly execute 7 ballistic wrist extension movements following an auditory cue. A 2-dimensional gyrometer is mounted on the dorsum of the hand to measure wrist extension movements. Electromyography (EMG) activity will be recorded on the extensor carpi ulnaris (ECU) muscle, a muscle that supports wrist extension movements.
Measured: 1 month post-stroke (subacute stroke), 6 months post-stroke (chronic stroke)
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted9 Sep 2015 (estimated)
- Study start5 Nov 2015
- Primary completion4 Feb 2021
- Study completion4 Feb 2021
Why it stopped: The study was suspended in 2020 due to COVID-19 safety measures. Follow up with those previously enrolled later resumed, but not all subjects returned due to the ongoing pandemic. The study closed after attempting to obtain as much data as possible.
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.
- Publications (3)Papers the sponsor has linked to this study.
- Other trials for StrokeStudies of the same condition, open and under way.
- More trials run by Emory UniversityThe 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
- Basic science
- Allocation
- Non-randomised
- Intervention model
- Parallel groups
- Masking
- Double blind
- Who is masked
- Participant, Investigator
- Enrolment
- 100 participants (actual)
Sponsor and investigators
- Lead sponsor
- Emory University
- Sponsor type
- University, hospital or other
- Collaborators
- National Institutes of Health (NIH), National Institute of Neurological Disorders and Stroke (NINDS), Eunice Kennedy Shriver National Institute of Child Health and Human Development (NICHD)
- Responsible party
- Principal investigator, Cathrin Buetefisch, Emory University
- Investigators
- Cathrin Buetefisch, MD, PhD, Principal investigator, Emory University
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT02544503
- Sponsor's protocol ID
- IRB00081238
- Other IDs
- R01NS090677
- Status last verified
- Aug 2023
- First submitted
- 7 Sep 2015
- Last updated
- 31 Aug 2023
- Results posted
- Yes, on ClinicalTrials.gov
- Data monitoring committee
- No
- FDA-regulated drug
- No
- FDA-regulated device
- Yes
- Individual data sharing
- No
Publications
Revill KP, Rizor E, Haut MW, Grafton ST, Buetefisch CM. Mean Motor Disconnectivity Predicts Hand Function Impairment After Stroke: Beyond Motor Cortex Output. Stroke. 2026 Apr;57(4):1057-1063. doi: 10.1161/STROKEAHA.125.052559. Epub 2026 Jan 7.
PubMed 41498148Wischnewski M, Edwards L, Revill KP, Drake D, Hobbs G, Buetefisch CM. Intensity-Dependent Effects of Low-Frequency Subthreshold rTMS on Primary Motor Cortex Excitability and Interhemispheric Inhibition in Elderly Participants: A Randomized Trial. Neurorehabil Neural Repair. 2025 Jan;39(1):58-73. doi: 10.1177/15459683241292615. Epub 2024 Oct 27.
PubMed 39462433Buetefisch CM, Haut MW, Revill KP, Shaeffer S, Edwards L, Barany DA, Belagaje SR, Nahab F, Shenvi N, Easley K. Stroke Lesion Volume and Injury to Motor Cortex Output Determines Extent of Contralesional Motor Cortex Reorganization. Neurorehabil Neural Repair. 2023 Feb-Mar;37(2-3):119-130. doi: 10.1177/15459683231152816. Epub 2023 Feb 14.
PubMed 36786394
Study at a glance
From the registry record, last updated by the sponsor on 31 Aug 2023. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Customized Cortical Stimulation Therapy in the Rehabilitation of Stroke Patients
- ClinicalTrials.gov ID
- NCT02544503
- Acronym / sponsor ID
- IRB00081238
- Conditions
- Stroke
- Keywords
- Subacute stroke, Chronic stroke
- Study type
- Interventional
- Recruitment status
- TerminatedReason stopped: The study was suspended in 2020 due to COVID-19 safety measures. Follow up with those previously enrolled later resumed, but not all subjects returned due to the ongoing pandemic. The study closed after attempting to obtain as much data as possible.
- Enrolment
- 100 participants (actual)
- Lead sponsor
- Emory UniversityUniversity, hospital or other
- Collaborators
- National Institutes of Health (NIH), National Institute of Neurological Disorders and Stroke (NINDS), Eunice Kennedy Shriver National Institute of Child Health and Human Development (NICHD)
- Study start
- 5 Nov 2015 (actual)
- Primary completion
- 4 Feb 2021 (actual)
- Study completion
- 4 Feb 2021 (actual)
- First posted
- 9 Sep 2015 (estimated)
- Results
- Posted 23 Aug 2022
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
The purpose of this study is to identify and establish how the area of the brain that controls motor function (motor cortex) of the non-affected hemisphere after stroke might serve as a new target for therapeutic interventions to improve motor performance after stroke.
Detailed description
It is well known that the motor area of one hemisphere of the brain (motor cortex) controls the movement of the opposite side of the body but the role of the motor cortex in the hemisphere spared by stroke (contralesional motor cortex) in motor performance during post stroke recovery is still unclear. It is also not clear whether the motor cortex of both hemispheres of the brain are involved, as movement becomes more complicated. Currently the role of the motor cortex on the same side of the body (referred to as ipsilateral motor cortex) in hand performance remains controversial. In most patients with stroke, only one side of the brain is affected by the stroke (affected hemisphere) resulting in weakness of half of the body opposite to the side of the stroke. Over the recent years, research has discovered that the side of the brain, that is spared by the stroke (non-affected hemisphere) may support recovery after stroke. However, there is also a question whether the non-affected hemisphere may interfere with the process of recovery. It is currently not known what factors influence the activity of non-affected hemisphere to either support or interfere with the recovery of stroke. A better understanding of those events is critical to development of optimal therapeutic strategies. For example, non-invasive stimulation of specific areas of the non-affected hemisphere may help to improve functional recovery following stroke. The objectives of this study are to define the factors that influence the activity in the non-affected hemisphere to either support or interfere with the recovery after stroke. The researchers will study the area of the brain that controls movements of the non-affected hemisphere as it relates to motor function post-stroke.
Transcranial magnetic stimulation (TMS) is a device that allows non-invasive stimulation of the brain. When the brain is stimulated repetitively at a very low rate and low intensity for about 15 minutes, the stimulated brain area becomes less active. This effect lasts 10 minutes and is called a "transient artificial lesion" as it mimics the effects of transiently interfering with the function of the stimulated brain area. The study includes experiments that first identify the extent of stroke and brain areas involved in a motor task using functional MRI of the brain and TMS. The researchers will then determine the functional role of the contralesional motor cortex by studying the effect of low frequency and high frequency repetitive transcranial magnetic stimulation (rTMS) of primary motor cortex (M1) on interhemispheric inhibition (IHI) (resting and active) and motor cortex excitability (short interval intracortical excitability and corticospinal excitability) and behavior. The researchers will thereby also identify rTMS protocols that enhance motor performance in stroke patients.
In this study the researchers will conduct experiments using repetitive TMS to downregulate the activity of the motor area and measures its effect on activity of motor cortex of both hemispheres. In addition to enrolling participants who have had a stroke, the researchers will enroll healthy participants as this collected data will provide normative values for task related changes in M1s and their interactions - a prerequisite to studying abnormalities in stroke patients during motor recovery. The measurements and interventions will occur at two time points in all participants with stroke (1 and 6 months post-stroke). The data will be compared to the results of healthy age matched controls, assessed at a single time point.
Study design
- Primary purpose
- Basic science
- Allocation
- Non-randomised
- Intervention model
- Parallel groups
- Masking
- Double blind (participant, investigator)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| Stroke Patients | Experimental | Device: Single-pulse Transcranial Magnetic Stimulation (TMS), Device: Paired-pulse Transcranial Magnetic Stimulation (ppTMS), Device: Low-frequency Repetitive Transcranial Magnetic Stimulation (rTMS), Device: Sham Motor Cortex StimulationSubjects will undergo single pulse transcranial magnetic stimulation (TMS), paired pulse transcranial stimulation (ppTMS), and low frequency repetitive transcranial magnetic stimulation (rTMS) at one month and six months post stroke. |
| Healthy Controls | Active comparator | Device: Single-pulse Transcranial Magnetic Stimulation (TMS), Device: Paired-pulse Transcranial Magnetic Stimulation (ppTMS), Device: Low-frequency Repetitive Transcranial Magnetic Stimulation (rTMS), Device: Sham Motor Cortex StimulationSubjects will undergo single pulse transcranial magnetic stimulation (TMS), paired pulse transcranial stimulation (ppTMS), and low frequency repetitive transcranial magnetic stimulation (rTMS) at one month and six months. |
Who may qualify
- Ages
- 40 to 80 years
- Sex
- All
- Healthy volunteers
- Accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (10 listed)
- The ability to provide informed consent
- Ages 40 to 80 years old
- Male or female
- One cerebral ischemic infarction less than 1 month affecting the primary motor output system of the hand at a cortical (M1) level as defined by magnetic resonance imaging (MRI) of the brain
- Paresis of the hand for more than 3 days after their cerebral infarction
Key exclusion criteria (10 listed)
- Neurological disorders other than stroke
- Aphasia that prevents following instructions or inability to communicate effectively with the study team
- Dementia
- Moderate or severe depression
- Contraindication to transcranial magnetic stimulation (TMS) and/or MRI
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 |
|---|---|---|
| Single-pulse Transcranial Magnetic Stimulation (TMS)Single-pulse Transcranial Magnetic Stimulation (TMS) is a brief magnetic pulse that is applied through a coil to the section of the head that overlays the motor cortex of the brain. Subjects will be comfortably seated in a dental chair surrounded by a frame that carries a coil holder to assist with the application of TMS to the brain. Single-pulse transcranial magnetic stimulation (TMS) will be administered at study visits. | Device | Healthy Controls, Stroke Patients |
| Paired-pulse Transcranial Magnetic Stimulation (ppTMS)Paired-pulse Transcranial Magnetic Stimulation (ppTMS) is two brief sequential magnetic pulses that are applied through a coil to the section of the head that overlays the motor cortex of the brain. Subjects will be comfortably seated in a dental chair surrounded by a frame that carries a coil holder to assist with the application of TMS to the brain. Paired-pulse transcranial magnetic stimulation (ppTMS) will be administered at study visits. | Device | Healthy Controls, Stroke Patients |
| Low-frequency Repetitive Transcranial Magnetic Stimulation (rTMS)Low-frequency Repetitive Transcranial Magnetic Stimulation (rTMS) is a sequence of brief magnetic pulses that are applied at 0.1 Hz frequency at low intensity through an air-cooled coil to the section of the head that overlays the motor cortex of the brain. Subjects will be comfortably seated in a dental chair surrounded by a frame that carries a coil holder to assist with the application of TMS to the brain. Low-frequency repetitive transcranial magnetic stimulation (rTMS) will be administered at study visits. | Device | Healthy Controls, Stroke Patients |
| Sham Motor Cortex StimulationSham motor cortex stimulation will be applied at study visits. | Device | Healthy Controls, Stroke Patients |
Primary outcome
Motor Function Assessed by the Jebsen Test
Time frame: 1 month post-stroke (subacute stroke), 6 months post-stroke (chronic stroke)
The Jebsen Test assesses weighted and non-weighted hand function among participants who have had a stroke. Subjects are assessed through writing, turning over 3 by 5 inch cards, picking up small common objects, simulated feeding, stacking checkers, picking up large objects, and picking up large heavy objects. Patients are required to perform all of the subtests with both the right and left hands. Time to complete each task is recorded and normalized to healthy age and sex matched control subjects. The score ranges from 0 to 1 with 0 being normal.
Mean Motor Evoked Potential (MEP) Amplitudes Assessed by Stimulus Response Curve (SRC) of the Contralesional M1
Time frame: 1 month post-stroke (subacute stroke) or single study visit for healthy controls, 6 months post-stroke (chronic stroke)
Change in mean motor evoked potential (MEP) amplitudes at each stimulus intensity will be calculated. The sum of these means is calculated as the area under the curve.
Presence of MEP in Response to TMS of the Ipsilesional M1
Time frame: 1 month post-stroke (subacute stroke), 6 months post-stroke (chronic stroke)
The presence of motor evoked potential (MEP) in response to maximum TMS applied to ipsilesional M1 was determined in participants with stroke.
Lesion Volume
Time frame: 1 month post-stroke (subacute stroke)
Normalized stroke lesion volume was determined at the one-month time point using structural MRI of the brain.
Corticospinal Tract (CST) Lesion
Time frame: 1 month post-stroke (subacute stroke)
Corticospinal tract (CST) lesion load will be determined at the one-month time point using structural MRI of the brain. The lesion size is expressed as percentage of the entire CST.
7 secondary outcomes
Motor Function Assessed by Time to Complete the Wolf Motor Function Test (WMFT)
Time frame: 1 month post-stroke (subacute stroke), 6 months post-stroke (chronic stroke)
Motor Function Assessed by Grip Strength During the Wolf Motor Function Test (WMFT)
Time frame: 1 month post-stroke (subacute stroke), 6 months post-stroke (chronic stroke)
Use of Paretic Arm Assessed by the Motor Activity Log (MAL)
Time frame: 1 month post-stroke (subacute stroke), 6 months post-stroke (chronic stroke)
CST Subpathway Originating in M1 Lesion Load
Time frame: 1 month post-stroke (subacute stroke)
Primary Motor Cortex (M1) Activity, Assessed by Functional Magnetic Resonance Imaging (fMRI)
Time frame: 1 month post-stroke (subacute stroke) or single study visit for healthy controls, 6 months post-stroke (chronic stroke)
Short Interval Cortical Inhibition (SICI) Measured by Repeated Transcranial Magnetic Stimulation (rTMS)
Time frame: 1 month post-stroke (subacute stroke) or single study visit for healthy controls, 6 months post-stroke (chronic stroke)
Peak Velocity During Wrist Extension Movement
Time frame: 1 month post-stroke (subacute stroke), 6 months post-stroke (chronic stroke)
Results and safety
Loading the posted results from ClinicalTrials.gov…
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 31 Aug 2023.
- Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
- Derived from this study: PubMed 41498148Revill KP, Rizor E, Haut MW, Grafton ST, Buetefisch CM. Mean Motor Disconnectivity Predicts Hand Function Impairment After Stroke: Beyond Motor Cortex Output. Stroke. 2026 Apr;57(4):1057-1063. doi: 10.1161/STROKEAHA.125.052559. Epub 2026 Jan 7.
- Derived from this study: PubMed 39462433Wischnewski M, Edwards L, Revill KP, Drake D, Hobbs G, Buetefisch CM. Intensity-Dependent Effects of Low-Frequency Subthreshold rTMS on Primary Motor Cortex Excitability and Interhemispheric Inhibition in Elderly Participants: A Randomized Trial. Neurorehabil Neural Repair. 2025 Jan;39(1):58-73. doi: 10.1177/15459683241292615. Epub 2024 Oct 27.
- Derived from this study: PubMed 36786394Buetefisch CM, Haut MW, Revill KP, Shaeffer S, Edwards L, Barany DA, Belagaje SR, Nahab F, Shenvi N, Easley K. Stroke Lesion Volume and Injury to Motor Cortex Output Determines Extent of Contralesional Motor Cortex Reorganization. Neurorehabil Neural Repair. 2023 Feb-Mar;37(2-3):119-130. doi: 10.1177/15459683231152816. Epub 2023 Feb 14.
- 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.
Cathrin Buetefisch, MD, PhD principal investigator
Emory University
3 sites in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A study testing Single-pulse Transcranial Magnetic Stimulation (TMS), Paired-pulse Transcranial Magnetic Stimulation (ppTMS) and Low-frequency Repetitive Transcranial Magnetic Stimulation (rTMS) in people with Stroke, run by Emory University at 3 sites 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 10 inclusion and 10 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: stopped early, as of the sponsor's last update on 31 Aug 2023. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 3 sites 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 23 Aug 2022). 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?
Motor Function Assessed by the Jebsen Test (time frame: 1 month post-stroke (subacute stroke), 6 months post-stroke (chronic stroke)). The study lists 5 primary outcomes in all. It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT02544503, which also lists 3 linked publications.
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 31 Aug 2023.