StrokeCAMNCT04286516
Brain Connections for Arm Movement After Stroke
A study testing Transcranial Magnetic Stimulation in people with Stroke and Brain Disease, run by VA Office of Research and Development at 1 site in United States.
Trial summary
The purpose of this study is to use Transcranial Magnetic Stimulation (TMS) while subjects are making reaching movements in a robotic arm device in order to discover how different brain areas control movement before and after stroke and when these brain areas are most sensitive to TMS. Read more about this study
- Who is it for?
- Ages 45 to 90 yearsHealthy volunteers can take part
- Conditions the study is for
- Stroke, Brain Disease, Central Nervous System Diseases
- What is being tested?
- Transcranial Magnetic Stimulation
- Type of treatment
- Medical device
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 76 participants
- Where
- 1 siteUnited States
- Study dates
- 10 Jan 2020to 1 Jun 2027
- Phase
- Interventional
- Are there results?
- Not yet: the study is under way
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 45 to 90 years
- All sexes
- Healthy volunteers accepted
- Adult, Older adult
Who may be able to join
- Be 45-90 years of age
- Have adequate language and neurocognitive function to participate in training and testing
- Be medically stable to participate in the study
- Be English speaking
- Be 45-90 years of age
- Clinically defined, unilateral, hemiparetic stroke with radiologic exclusion of other possible diagnosis
Show all 11Show fewer
- Stroke onset at least 6 months before enrollment
- Subcortical stroke (ex: internal capsule, deep white matter of posterior frontal lobe)
- Present with mild to moderate arm dysfunction
- Be medically stable to participate in the study
- Be English speaking
Who cannot join
- (for both groups)
- Unable to give informed consent
- Have a serious complicating medical illness that would preclude participation
- Contractures or orthopedic problems limiting range of joint motion in the potential study arm or other impairments that would interfere with the study activities
- Visual loss such that the subject would not be able to see the test patterns on the robot computer monitor
- Unable to comply with requirements of the study
Show all 9Show fewer
- Enrollment in another greater-than-minimal risk study
- Presence of medical condition or implant that prevents safe administration of TMS or MRI
- Pregnancy
Trial locations and contacts
1 site in 1 country. Contact the study team or a site near you to ask about taking part.
United States1 site, 1 recruiting
- Recruiting
VA Pittsburgh Healthcare System University Drive Division, Pittsburgh, PA
Pittsburgh, Pennsylvania, 15240
George F Wittenberg, MD PhD, (412) 360-6185, George.Wittenberg@va.gov
Amy Boos, (412) 648-4179, amy.boos2@va.gov
About this study
Official title: Brain Areas That Control Reaching Movements After Stroke: Task-relevant Connectivity and Movement-synchronized Brain Stimulation
The purpose of this study is to use Transcranial Magnetic Stimulation (TMS) while subjects are making reaching movements in a robotic arm device in order to discover how different brain areas control movement before and after stroke and when these brain areas are most sensitive to TMS.
Read the detailed description
The general objective of this application is to study reorganization of network interactions following a common type of subcortical stroke (i.e. internal capsule) with mechanistic studies using noninvasive neurophysiology in humans. The goal is to obtain pilot data and to demonstrate the feasibility of the approach that combines transcranial magnetic stimulation (TMS) with reaching in an advanced exoskeleton robot. As reaching is an essential part of many daily activities, this approach will have beneficial impacts on the quality of life of these stroke patients.
The central hypothesis is that bilateral premotor cortical areas, dorsal (PMd) more so than ventral (PMv,) develops greater connectivity with primary motor cortex (M1) after stroke and thus better ability to produce motor outputs that support reaching with the paretic arm. When there is more damage to the corticospinal tract, contralesional areas will take on a greater role.
The relationship between connectivity, behavioral effects of stimulation and motor performance will be established. These findings will allow the investigators to formulate clear hypotheses about which premotor area should be modulated with TMS, depending on stroke extent and deficits in motor control, when reaching the stage of proposing a treatment trial. Increased knowledge of the dynamic changes of physiological interactions during various phases of reaching movements will allow a more defined study regarding the role of premotor areas in recovery of motor function after stroke, and a novel treatment protocol that delivers precisely timed stimulations during practice of reaching movements. Ultimately, the investigators can test these novel treatments in clinical trials and compare their impact to other, less specific, neuromodulatory methods such as transcranial direct current stimulation. This study will also lay the groundwork for collaboration in brain computer interface and non-human primate investigations in the mechanisms and treatment of motor deficits after stroke.
- Conditions
- Stroke, Brain Disease, Central Nervous System Diseases, Nervous System Diseases, Cardiovascular Diseases
- Being tested
- Transcranial Magnetic Stimulation
- Medical subject headings
- Stroke, Brain Diseases, Central Nervous System Diseases, Nervous System Diseases, Cardiovascular Diseases
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Transcranial Magnetic StimulationDevice
Paired pulse transcranial magnetic stimulation
| Study group | Role | What they receive |
|---|---|---|
| Reaching with TMS | Experimental | All participants enrolled in this group will receive TMS while performing reaching movements in a robotic system. Receives: Device: Transcranial Magnetic Stimulation |
What is being measured
The primary outcome is the main question the study is designed to answer.
Path length
Movement path length in centimeters from KINARM system during the one second reaching period. (units: cm)
Measured: Immediate (within 2 s after stimulation)
Secondary outcomes (4)
Times
Specific kinematic data from KINARM system: reaction time, movement time to reach target (units: ms)
Measured: Immediate (within 2 s after stimulation)
Velocities
maximum velocity reached during reach (units: cm/s)
Measured: Immediate (within 2 s after stimulation)
Accuracy
specific position data from KINARM system: target accuracy, distance from manipulandum position at end of one second reaching period to target center. (units: cm.)
Measured: Immediate (within 2 s after stimulation)
EMG
Electromyographic data from surface electrodes on biceps, triceps, anterior deltoid, and posterior deltoid muscles - These signals will be rectified and normalized to the maximum values during practice reaches. (units: mV/mV - dimensionless).
Measured: Immediate (within 2 s after stimulation)
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted27 Feb 2020
- Study start10 Jan 2020
- Primary completion1 Sep 2026 (estimated)
- Study completion1 Jun 2027 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (13)Papers the sponsor has linked to this study.
- Other trials for StrokeStudies of the same condition, open and under way.
- More trials run by VA Office of Research and DevelopmentThe 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
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Model description
- Controlled, nonrandomized experimental study
- Masking
- None (open label)
- Enrolment
- 76 participants (estimated)
Sponsor and investigators
- Lead sponsor
- VA Office of Research and Development
- Sponsor type
- US federal agency
- Collaborators
- VA Pittsburgh Healthcare System, University of Pittsburgh
- Responsible party
- Sponsor
- Investigators
- George F. Wittenberg, MD PhD, Principal investigator, VA Pittsburgh Healthcare System University Drive Division, Pittsburgh, PA
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT04286516
- Sponsor's protocol ID
- N3511-R
- Other IDs
- Pro00003163
- Acronym
- CAM
- Status last verified
- May 2026
- First submitted
- 21 Jan 2020
- Last updated
- 2 Jun 2026
- Results posted
- No
- Data monitoring committee
- No
- FDA-regulated drug
- No
- FDA-regulated device
- Yes
- Individual data sharing
- No: Research information will not be shared with anyone outside of the research team.
Publications
Johansen-Berg H, Rushworth MF, Bogdanovic MD, Kischka U, Wimalaratna S, Matthews PM. The role of ipsilateral premotor cortex in hand movement after stroke. Proc Natl Acad Sci U S A. 2002 Oct 29;99(22):14518-23. doi: 10.1073/pnas.222536799. Epub 2002 Oct 10.
PubMed 12376621Butefisch CM, Kleiser R, Korber B, Muller K, Wittsack HJ, Homberg V, Seitz RJ. Recruitment of contralesional motor cortex in stroke patients with recovery of hand function. Neurology. 2005 Mar 22;64(6):1067-9. doi: 10.1212/01.WNL.0000154603.48446.36.
PubMed 15781831Corbett D, Carmichael ST, Murphy TH, Jones TA, Schwab ME, Jolkkonen J, Clarkson AN, Dancause N, Weiloch T, Johansen-Berg H, Nilsson M, McCullough LD, Joy MT. Enhancing the Alignment of the Preclinical and Clinical Stroke Recovery Research Pipeline: Consensus-Based Core Recommendations From the Stroke Recovery and Rehabilitation Roundtable Translational Working Group. Neurorehabil Neural Repair. 2017 Aug;31(8):699-707. doi: 10.1177/1545968317724285.
PubMed 28803530Nudo RJ, Wise BM, SiFuentes F, Milliken GW. Neural substrates for the effects of rehabilitative training on motor recovery after ischemic infarct. Science. 1996 Jun 21;272(5269):1791-4. doi: 10.1126/science.272.5269.1791.
PubMed 8650578Frost SB, Barbay S, Friel KM, Plautz EJ, Nudo RJ. Reorganization of remote cortical regions after ischemic brain injury: a potential substrate for stroke recovery. J Neurophysiol. 2003 Jun;89(6):3205-14. doi: 10.1152/jn.01143.2002.
PubMed 12783955Dancause N, Barbay S, Frost SB, Zoubina EV, Plautz EJ, Mahnken JD, Nudo RJ. Effects of small ischemic lesions in the primary motor cortex on neurophysiological organization in ventral premotor cortex. J Neurophysiol. 2006 Dec;96(6):3506-11. doi: 10.1152/jn.00792.2006. Epub 2006 Sep 20.
PubMed 16987930Dancause N, Barbay S, Frost SB, Plautz EJ, Chen D, Zoubina EV, Stowe AM, Nudo RJ. Extensive cortical rewiring after brain injury. J Neurosci. 2005 Nov 2;25(44):10167-79. doi: 10.1523/JNEUROSCI.3256-05.2005.
PubMed 16267224Quessy S, Cote SL, Hamadjida A, Deffeyes J, Dancause N. Modulatory Effects of the Ipsi and Contralateral Ventral Premotor Cortex (PMv) on the Primary Motor Cortex (M1) Outputs to Intrinsic Hand and Forearm Muscles in Cebus apella. Cereb Cortex. 2016 Oct;26(10):3905-20. doi: 10.1093/cercor/bhw186. Epub 2016 Jul 29.
PubMed 27473318Kurata K. Premotor cortex of monkeys: set- and movement-related activity reflecting amplitude and direction of wrist movements. J Neurophysiol. 1993 Jan;69(1):187-200. doi: 10.1152/jn.1993.69.1.187.
PubMed 8433130Davare M, Duque J, Vandermeeren Y, Thonnard JL, Olivier E. Role of the ipsilateral primary motor cortex in controlling the timing of hand muscle recruitment. Cereb Cortex. 2007 Feb;17(2):353-62. doi: 10.1093/cercor/bhj152. Epub 2006 Mar 8.
PubMed 16525129Weiller C, Ramsay SC, Wise RJ, Friston KJ, Frackowiak RS. Individual patterns of functional reorganization in the human cerebral cortex after capsular infarction. Ann Neurol. 1993 Feb;33(2):181-9. doi: 10.1002/ana.410330208.
PubMed 8434880Wittenberg GF, Richards LG, Jones-Lush LM, Roys SR, Gullapalli RP, Yang S, Guarino PD, Lo AC. Predictors and brain connectivity changes associated with arm motor function improvement from intensive practice in chronic stroke. F1000Res. 2016 Aug 31;5:2119. doi: 10.12688/f1000research.8603.2. eCollection 2016.
PubMed 28357039Haddadshargh G, de Freitas RM, Mak J, Boos A, Fang X, Collinger JL, McKernan G, Zhan L, Liu F, Wittenberg GF. Mapping the Causal Roles of Non-Primary Motor Areas in Human Reach Planning and Execution. Hum Brain Mapp. 2026 Feb 1;47(2):e70465. doi: 10.1002/hbm.70465.
PubMed 41641924
Study at a glance
From the registry record, last updated by the sponsor on 2 Jun 2026. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Brain Areas That Control Reaching Movements After Stroke: Task-relevant Connectivity and Movement-synchronized Brain Stimulation
- ClinicalTrials.gov ID
- NCT04286516
- Acronym / sponsor ID
- CAM / N3511-R
- Conditions
- Stroke, Brain Disease, Central Nervous System Diseases, Nervous System Diseases, Cardiovascular Diseases
- Study type
- Interventional
- Recruitment status
- Recruiting
- Enrolment
- 76 participants (estimated)
- Lead sponsor
- VA Office of Research and DevelopmentUS federal agency
- Collaborators
- VA Pittsburgh Healthcare System, University of Pittsburgh
- Study start
- 10 Jan 2020 (actual)
- Primary completion
- 1 Sep 2026 (estimated)
- Study completion
- 1 Jun 2027 (estimated)
- First posted
- 27 Feb 2020 (actual)
- Results
- Not posted in the source record
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 use Transcranial Magnetic Stimulation (TMS) while subjects are making reaching movements in a robotic arm device in order to discover how different brain areas control movement before and after stroke and when these brain areas are most sensitive to TMS.
Detailed description
The general objective of this application is to study reorganization of network interactions following a common type of subcortical stroke (i.e. internal capsule) with mechanistic studies using noninvasive neurophysiology in humans. The goal is to obtain pilot data and to demonstrate the feasibility of the approach that combines transcranial magnetic stimulation (TMS) with reaching in an advanced exoskeleton robot. As reaching is an essential part of many daily activities, this approach will have beneficial impacts on the quality of life of these stroke patients.
The central hypothesis is that bilateral premotor cortical areas, dorsal (PMd) more so than ventral (PMv,) develops greater connectivity with primary motor cortex (M1) after stroke and thus better ability to produce motor outputs that support reaching with the paretic arm. When there is more damage to the corticospinal tract, contralesional areas will take on a greater role.
The relationship between connectivity, behavioral effects of stimulation and motor performance will be established. These findings will allow the investigators to formulate clear hypotheses about which premotor area should be modulated with TMS, depending on stroke extent and deficits in motor control, when reaching the stage of proposing a treatment trial. Increased knowledge of the dynamic changes of physiological interactions during various phases of reaching movements will allow a more defined study regarding the role of premotor areas in recovery of motor function after stroke, and a novel treatment protocol that delivers precisely timed stimulations during practice of reaching movements. Ultimately, the investigators can test these novel treatments in clinical trials and compare their impact to other, less specific, neuromodulatory methods such as transcranial direct current stimulation. This study will also lay the groundwork for collaboration in brain computer interface and non-human primate investigations in the mechanisms and treatment of motor deficits after stroke.
Study design
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Number of arms
- 1
- Model description
- Controlled, nonrandomized experimental study
| Arm | Type | Receives |
|---|---|---|
| Reaching with TMS | Experimental | Device: Transcranial Magnetic StimulationAll participants enrolled in this group will receive TMS while performing reaching movements in a robotic system. |
Who may qualify
- Ages
- 45 to 90 years
- Sex
- All
- Healthy volunteers
- Accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (11 listed)
- Be 45-90 years of age
- Have adequate language and neurocognitive function to participate in training and testing
- Be medically stable to participate in the study
- Be English speaking
- Be 45-90 years of age
Key exclusion criteria (9 listed)
- (for both groups)
- Unable to give informed consent
- Have a serious complicating medical illness that would preclude participation
- Contractures or orthopedic problems limiting range of joint motion in the potential study arm or other impairments that would interfere with the study activities
- Visual loss such that the subject would not be able to see the test patterns on the robot computer monitor
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 |
|---|---|---|
| Transcranial Magnetic StimulationPaired pulse transcranial magnetic stimulation | Device | Reaching with TMS |
Primary outcome
Path length
Time frame: Immediate (within 2 s after stimulation)
Movement path length in centimeters from KINARM system during the one second reaching period. (units: cm)
4 secondary outcomes
Times
Time frame: Immediate (within 2 s after stimulation)
Velocities
Time frame: Immediate (within 2 s after stimulation)
Accuracy
Time frame: Immediate (within 2 s after stimulation)
EMG
Time frame: Immediate (within 2 s after stimulation)
Results and safety
This study is still under way. Results are not available in the source record yet.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 2 Jun 2026.
- Background: PubMed 12376621Johansen-Berg H, Rushworth MF, Bogdanovic MD, Kischka U, Wimalaratna S, Matthews PM. The role of ipsilateral premotor cortex in hand movement after stroke. Proc Natl Acad Sci U S A. 2002 Oct 29;99(22):14518-23. doi: 10.1073/pnas.222536799. Epub 2002 Oct 10.
- Background: PubMed 15781831Butefisch CM, Kleiser R, Korber B, Muller K, Wittsack HJ, Homberg V, Seitz RJ. Recruitment of contralesional motor cortex in stroke patients with recovery of hand function. Neurology. 2005 Mar 22;64(6):1067-9. doi: 10.1212/01.WNL.0000154603.48446.36.
- Background: PubMed 28803530Corbett D, Carmichael ST, Murphy TH, Jones TA, Schwab ME, Jolkkonen J, Clarkson AN, Dancause N, Weiloch T, Johansen-Berg H, Nilsson M, McCullough LD, Joy MT. Enhancing the Alignment of the Preclinical and Clinical Stroke Recovery Research Pipeline: Consensus-Based Core Recommendations From the Stroke Recovery and Rehabilitation Roundtable Translational Working Group. Neurorehabil Neural Repair. 2017 Aug;31(8):699-707. doi: 10.1177/1545968317724285.
- Background: PubMed 8650578Nudo RJ, Wise BM, SiFuentes F, Milliken GW. Neural substrates for the effects of rehabilitative training on motor recovery after ischemic infarct. Science. 1996 Jun 21;272(5269):1791-4. doi: 10.1126/science.272.5269.1791.
- Background: PubMed 12783955Frost SB, Barbay S, Friel KM, Plautz EJ, Nudo RJ. Reorganization of remote cortical regions after ischemic brain injury: a potential substrate for stroke recovery. J Neurophysiol. 2003 Jun;89(6):3205-14. doi: 10.1152/jn.01143.2002.
- Background: PubMed 16987930Dancause N, Barbay S, Frost SB, Zoubina EV, Plautz EJ, Mahnken JD, Nudo RJ. Effects of small ischemic lesions in the primary motor cortex on neurophysiological organization in ventral premotor cortex. J Neurophysiol. 2006 Dec;96(6):3506-11. doi: 10.1152/jn.00792.2006. Epub 2006 Sep 20.
- Background: PubMed 16267224Dancause N, Barbay S, Frost SB, Plautz EJ, Chen D, Zoubina EV, Stowe AM, Nudo RJ. Extensive cortical rewiring after brain injury. J Neurosci. 2005 Nov 2;25(44):10167-79. doi: 10.1523/JNEUROSCI.3256-05.2005.
- Background: PubMed 27473318Quessy S, Cote SL, Hamadjida A, Deffeyes J, Dancause N. Modulatory Effects of the Ipsi and Contralateral Ventral Premotor Cortex (PMv) on the Primary Motor Cortex (M1) Outputs to Intrinsic Hand and Forearm Muscles in Cebus apella. Cereb Cortex. 2016 Oct;26(10):3905-20. doi: 10.1093/cercor/bhw186. Epub 2016 Jul 29.
- Background: PubMed 8433130Kurata K. Premotor cortex of monkeys: set- and movement-related activity reflecting amplitude and direction of wrist movements. J Neurophysiol. 1993 Jan;69(1):187-200. doi: 10.1152/jn.1993.69.1.187.
- Background: PubMed 16525129Davare M, Duque J, Vandermeeren Y, Thonnard JL, Olivier E. Role of the ipsilateral primary motor cortex in controlling the timing of hand muscle recruitment. Cereb Cortex. 2007 Feb;17(2):353-62. doi: 10.1093/cercor/bhj152. Epub 2006 Mar 8.
- Background: PubMed 8434880Weiller C, Ramsay SC, Wise RJ, Friston KJ, Frackowiak RS. Individual patterns of functional reorganization in the human cerebral cortex after capsular infarction. Ann Neurol. 1993 Feb;33(2):181-9. doi: 10.1002/ana.410330208.
- Background: PubMed 28357039Wittenberg GF, Richards LG, Jones-Lush LM, Roys SR, Gullapalli RP, Yang S, Guarino PD, Lo AC. Predictors and brain connectivity changes associated with arm motor function improvement from intensive practice in chronic stroke. F1000Res. 2016 Aug 31;5:2119. doi: 10.12688/f1000research.8603.2. eCollection 2016.
- Individual participant dataSharing planned: No. Research information will not be shared with anyone outside of the research team.
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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.
George F. Wittenberg, MD PhD principal investigator
VA Pittsburgh Healthcare System University Drive Division, Pittsburgh, PA
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A study testing Transcranial Magnetic Stimulation in people with Stroke and Brain Disease, run by VA Office of Research and Development at 1 site 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 11 inclusion and 9 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: looking for participants now, as of the sponsor's last update on 2 Jun 2026. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site 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?
This study is still under way. Results are not available in the source record yet.
How can a doctor refer a patient or contact the research team?
Contact Amy Boos ((412) 648-4179, amy.boos2@va.gov), or a site near the patient. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Path length (time frame: Immediate (within 2 s after stimulation)). 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 NCT04286516, which also lists 13 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 2 Jun 2026.