StrokeEarly Phase 1NCT03584425
Imaging Laterality in Chronic Stroke Patients
A Early Phase 1 study testing Rasch modified version of the Fugl-Meyer Motor assessment, Anatomical image acquisition and Functional MRI task and acquisition in people with Stroke and Motor Cortex; Lesion, run by Medical University of South Carolina at 1 site in United States.
Trial summary
In healthy individuals, unimanual movement (with either the left or right hand) is associated with activity in a network of predominantly contralateral brain regions, including the primary motor cortex (PMC). This laterality is often compromised following a middle cerebral artery (MCA) stroke. Read more about this study
- Who is it for?
- Ages 21 to 80 yearsHealthy volunteers can take part
- Conditions the study is for
- Stroke, Motor Cortex; Lesion
- What is being tested?
- Rasch modified version of the Fugl-Meyer Motor assessment, Anatomical image acquisition and Functional MRI task and acquisition
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 44 participants
- Where
- 1 siteUnited States
- Study dates
- 15 Dec 2014to 30 May 2019
- Phase
- Early Phase 1
- Are there results?
- None posted in the registry
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 21 to 80 years
- All sexes
- Healthy volunteers accepted
- Adult, Older adult
Who may be able to join
- 21-80 years old of any race and ethnicity
- At least 2 cardiovascular risk factors (smoking, high blood pressure, high cholesterol, diabetes, overweight, age (>55 for men, >65 for women), family history of stroke).
- Left middle cerebral artery ischemic stroke with at least 6 month chronicity
- Right upper extremity weakness with a Rasch-modified Fugl-Meyer upper extremity score of 20 to 50
- Ability to voluntarily flex the affected elbow and shoulder from 10-75% of the normal range
- Ability to make a fist and relax the affected hand (note: this motion will be required in the functional MRI task)
Who cannot join
- Primary intracerebral hematoma or subarachnoid hemorrhage
- Bi-hemispheric ischemic strokes
- History of prior right-sided stroke or old infarct demonstrated on the CT or MRI or documented in medical records
- Other concomitant neurological disorders affecting upper extremity motor function
- Documented history of dementia before or after stroke
- Presence of any MRI, TMS, or transcranial direct current stimulation risk factors such as an electrically, magnetically or mechanically activated metal or nonmetal implant including cardiac pacemaker, intracerebral vascular clips or any other electrically sensitive support system
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- Pregnancy as the effect of MRI on the fetus is unknown, females of child bearing age must undergo a pregnancy test to confirm eligibility
- History of seizure disorder or post-stroke seizure
- Preexisting scalp lesion or wound or bone defect or hemicraniectomy
- Left-hand dominance (before the stroke in the stroke patients) as the typical pattern of laterality is not as strong in left-handed healthy individuals
- Current nicotine dependence (Note: nicotine use is not an exclusionary criteria as there is no known association between acute use and BOLD signal changes in non-dependent smokers)
Trial locations and contacts
1 site in 1 country.
United States1 site
Medical University of South Carolina
Charleston, South Carolina, 29425
About this study
Official title: Investigating the Neurobiologic Basis for Loss of Cortical Laterality in Chronic Stroke Patients
In healthy individuals, unimanual movement (with either the left or right hand) is associated with activity in a network of predominantly contralateral brain regions, including the primary motor cortex (PMC). This laterality is often compromised following a middle cerebral artery (MCA) stroke. Neuroimaging studies of these patients have shown that unimanual movements with the effected hand are associated with elevated Blood Oxygen-Level Dependent (BOLD) signal in both the lesioned and the nonlesioned primary motor cortices. Elevated activity in the contralesional PMC is well-established in chronic stroke patients and is associated with poor motor rehabilitation outcomes. Yet the neurobiologic basis for this aberrant neural activity is equivocal. The overarching goal of this project is to determine the neurobiologic basis for elevated activity in the contralesional primary motor cortex.
Read the detailed description
One factor that may contribute to elevated activity in the contralesional PMC is increased cortical excitatory tone within the contralesional hemisphere (Aim 1).
While approximately 80% of the descending corticospinal neurons that control the right hand originate in the left PMC, 20% originate in the right PMC. Elevated activity in the right PMC of left-sided stroke patients may reflect compensatory activity of these descending fibers. Neural activity in the PMC reflects the balance of local excitatory (glutamatergic) and inhibitory (GABAergic) processing. It can be measured in two manners: 1) electrophysiologically, using single hemisphere paired pulse transcranial magnetic stimulation (TMS), and 2) neurochemically, using magnetic resonance spectroscopy (MRS).
Another factor that may contribute to elevated activity in the contralesional PMC is a loss of transcallosal inhibition between the hemispheres (Aim 2). During right hand movement, the left PMC of healthy individuals actively inhibits the right PMC via inhibitory projections through the corpus callosum. In left MCA stroke patients, elevated activity in the contralesional (right) PMC when moving the right hand may reflect a loss of typical inhibition from the left PMC. The integrity of inter-hemispheric information transfer can be measured in two manners: 1) using bi-hemispheric paired-pulse TMS, and 2) using a multimodal brain stimulation/brain imaging approach, interleaved TMS/MRI.
Through interleaved TMS/MRI, the investigators can selectively stimulate the ipsilesional PMC and quantify the amount of TMS-induced activity in the contralesional PMC. These two explanations will be tested through a cross-sectional investigation of neural function in left MCA stroke patients with mild-moderate right upper extremity impairment and controls matched for age and cardiovascular risk factors. To assess the clinical relevance of these factors on motor dysfunction, the investigators will perform a detailed kinematic assessment of movement efficiency, smoothness and compensation (Aim 3).
- Conditions
- Stroke, Motor Cortex; Lesion
- Being tested
- Rasch modified version of the Fugl-Meyer Motor assessment, Anatomical image acquisition, Functional MRI task and acquisition
- Keywords
- BOLD Signal, Functional Magnetic Resonance Imaging, MR Spectroscopy, Anatomical Imaging, Kinematics
- Medical subject headings
- Stroke
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Rasch modified version of the Fugl-Meyer Motor assessmentDiagnostic test
All participants will receive a comprehensive clinical assessment of motor function including the Rasch modified version of the Fugl-Meyer Motor assessment and a kinematic assessment of unimanual and bimanual movements using a 45 sensor 3D active marker based motion capture system. The three primary measures investigated in the kinematics include: 1) movement efficiency, 2) movement smoothness, and 3) motor compensation.
Anatomical image acquisitionDiagnostic test
High-resolution structural scans will be obtained using an inversion recovery 3D spoiled gradient echo (3DSPGR) sequence using a matrix size of 256 x 256, field of view of 24 cm, section thickness of 1.5 mm with no gap between sections, and 128 slices, giving an in-plane resolution of 0.94 mm. This sequence will be used for anatomic overlays of the functional data and for spatial normalization to a standard atlas.
Functional MRI task and acquisitionDiagnostic test
Briefly, patients will be given two pressure-sensitive bulbs (one to be held in each hand and fastened lightly to their wrists with Velcro such that they do not drop it during the scan. During two 2½ minute runs they will be prompted to squeeze the bulb in either their affected or unaffected hand in blocks of 15 seconds. These blocks will be interspersed with blocks of rest. The pressure from the bulbs will be digitally recorded and quantified offline in order to: 1) verify that the patient was squeezing the ball, and 2) assess the presence of 'mirror movements' from the opposing hand that may inform the imaging results regarding loss of laterality).
| Study group | Role | What they receive |
|---|---|---|
| Healthy Controls | Experimental | Subjects will undergo the following diagnostic tasks and assessments: Rasch Modified Version of the Fugl-Meyer Motor Assessment, Anatomical Image Acquisition, and the Functional MRI Task and Acquisition Receives: Diagnostic Test: Rasch modified version of the Fugl-Meyer Motor assessment; Diagnostic Test: Anatomical image acquisition; Diagnostic Test: Functional MRI task and acquisition |
| Stroke Participants | Experimental | Subjects will undergo the following diagnostic tasks and assessments: Rasch Modified Version of the Fugl-Meyer Motor Assessment, Anatomical Image Acquisition, and the Functional MRI Task and Acquisition Receives: Diagnostic Test: Rasch modified version of the Fugl-Meyer Motor assessment; Diagnostic Test: Anatomical image acquisition; Diagnostic Test: Functional MRI task and acquisition |
What is being measured
The primary outcome is the main question the study is designed to answer.
Compare the ratio of gluatamte and gaba concentrations within the contralesional primary motor cortex
Using spectroscopy investigators will determine if the ratio of glutamate/GABA is higher in stroke patients than controls. Furthermore, in healthy controls prepulse inhibition will be positively correlated with the concentration of GABA, and prepulse facilitation will be positively correlated with the concentration of glutamate. Although we expect this relationship to be true in both the controls and the stroke patients, variation from this pattern in the stroke patients would suggest that there is another factor beyond simple within-hemisphere measurements that is affecting the contralesional cortex activity.
Measured: Through study completion, an average of two weeks
Secondary outcomes (1)
Quantify the relationship between neural activity and motor performance using the Rasch modified version of the Fugl-Meyer motor assessment battery to acquire three aspects of motor performance for all individuals in both groups.
Impairment on bimanual tasks will be related to the outcome measures of previous Aims. That is, individuals with less transcallosal inhibition will perform worse on the bimanual task (less efficiency and smoothness) than individuals with transcallosal inhibition closer to healthy controls. This is based on pilot data from Dr. Woodbury of the Quantitative Behavioral Assessment and Rehabilitation Core that suggests during bimanual tasks the kinetics of the impaired arm remain the same but the previously unimpaired limb performs worse. This suggests that loss of inhibition 'infects' the arm movement typically controlled by the contralesional hemisphere.
Measured: Through study completion, an average of two weeks
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted12 Jul 2018
- Study start15 Dec 2014
- Primary completion30 May 2019
- Study completion30 May 2019
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for StrokeStudies of the same condition, open and under way.
- 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
- Early Phase 1
- Primary purpose
- Diagnosis
- Allocation
- Non-randomised
- Intervention model
- Parallel groups
- Model description
- The investigators will enroll a total of 30 chronic stroke patients and 30 neurologically healthy controls matched for age and with at least 2 cardiovascular risk factors
- Masking
- None (open label)
- Enrolment
- 44 participants (actual)
Sponsor and investigators
- Lead sponsor
- Medical University of South Carolina
- Sponsor type
- University, hospital or other
- Collaborators
- MUSC Center for Biomedical Research Excellence in Stroke Recovery
- Responsible party
- Sponsor
- Investigators
- Colleen A Hanlon, PhD, Principal investigator, Medical University of South Carolina
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT03584425
- Sponsor's protocol ID
- 31250
- Status last verified
- Jul 2019
- First submitted
- 15 Jun 2018
- Last updated
- 23 Jul 2019
- Results posted
- No
- Data monitoring committee
- Yes
- FDA-regulated drug
- No
- FDA-regulated device
- No
- Individual data sharing
- Yes: Yes The data from the primary outcome measurement will be shared via manuscripts and after study completion by request to the Principal Investigator
Study at a glance
From the registry record, last updated by the sponsor on 23 Jul 2019. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Investigating the Neurobiologic Basis for Loss of Cortical Laterality in Chronic Stroke Patients
- ClinicalTrials.gov ID
- NCT03584425
- Acronym / sponsor ID
- 31250
- Conditions
- Stroke, Motor Cortex; Lesion
- Keywords
- BOLD Signal, Functional Magnetic Resonance Imaging, MR Spectroscopy, Anatomical Imaging, Kinematics
- Phase
- Early Phase 1
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 44 participants (actual)
- Lead sponsor
- Medical University of South CarolinaUniversity, hospital or other
- Collaborators
- MUSC Center for Biomedical Research Excellence in Stroke Recovery
- Study start
- 15 Dec 2014 (actual)
- Primary completion
- 30 May 2019 (actual)
- Study completion
- 30 May 2019 (actual)
- First posted
- 12 Jul 2018 (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.
In healthy individuals, unimanual movement (with either the left or right hand) is associated with activity in a network of predominantly contralateral brain regions, including the primary motor cortex (PMC). This laterality is often compromised following a middle cerebral artery (MCA) stroke. Neuroimaging studies of these patients have shown that unimanual movements with the effected hand are associated with elevated Blood Oxygen-Level Dependent (BOLD) signal in both the lesioned and the nonlesioned primary motor cortices. Elevated activity in the contralesional PMC is well-established in chronic stroke patients and is associated with poor motor rehabilitation outcomes. Yet the neurobiologic basis for this aberrant neural activity is equivocal. The overarching goal of this project is to determine the neurobiologic basis for elevated activity in the contralesional primary motor cortex.
Detailed description
One factor that may contribute to elevated activity in the contralesional PMC is increased cortical excitatory tone within the contralesional hemisphere (Aim 1).
While approximately 80% of the descending corticospinal neurons that control the right hand originate in the left PMC, 20% originate in the right PMC. Elevated activity in the right PMC of left-sided stroke patients may reflect compensatory activity of these descending fibers. Neural activity in the PMC reflects the balance of local excitatory (glutamatergic) and inhibitory (GABAergic) processing. It can be measured in two manners: 1) electrophysiologically, using single hemisphere paired pulse transcranial magnetic stimulation (TMS), and 2) neurochemically, using magnetic resonance spectroscopy (MRS).
Another factor that may contribute to elevated activity in the contralesional PMC is a loss of transcallosal inhibition between the hemispheres (Aim 2). During right hand movement, the left PMC of healthy individuals actively inhibits the right PMC via inhibitory projections through the corpus callosum. In left MCA stroke patients, elevated activity in the contralesional (right) PMC when moving the right hand may reflect a loss of typical inhibition from the left PMC. The integrity of inter-hemispheric information transfer can be measured in two manners: 1) using bi-hemispheric paired-pulse TMS, and 2) using a multimodal brain stimulation/brain imaging approach, interleaved TMS/MRI.
Through interleaved TMS/MRI, the investigators can selectively stimulate the ipsilesional PMC and quantify the amount of TMS-induced activity in the contralesional PMC. These two explanations will be tested through a cross-sectional investigation of neural function in left MCA stroke patients with mild-moderate right upper extremity impairment and controls matched for age and cardiovascular risk factors. To assess the clinical relevance of these factors on motor dysfunction, the investigators will perform a detailed kinematic assessment of movement efficiency, smoothness and compensation (Aim 3).
Study design
- Primary purpose
- Diagnosis
- Allocation
- Non-randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Number of arms
- 2
- Model description
- The investigators will enroll a total of 30 chronic stroke patients and 30 neurologically healthy controls matched for age and with at least 2 cardiovascular risk factors
| Arm | Type | Receives |
|---|---|---|
| Healthy Controls | Experimental | Diagnostic Test: Rasch modified version of the Fugl-Meyer Motor assessment, Diagnostic Test: Anatomical image acquisition, Diagnostic Test: Functional MRI task and acquisitionSubjects will undergo the following diagnostic tasks and assessments: Rasch Modified Version of the Fugl-Meyer Motor Assessment, Anatomical Image Acquisition, and the Functional MRI Task and Acquisition |
| Stroke Participants | Experimental | Diagnostic Test: Rasch modified version of the Fugl-Meyer Motor assessment, Diagnostic Test: Anatomical image acquisition, Diagnostic Test: Functional MRI task and acquisitionSubjects will undergo the following diagnostic tasks and assessments: Rasch Modified Version of the Fugl-Meyer Motor Assessment, Anatomical Image Acquisition, and the Functional MRI Task and Acquisition |
Who may qualify
- Ages
- 21 to 80 years
- Sex
- All
- Healthy volunteers
- Accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (6 listed)
- 21-80 years old of any race and ethnicity
- At least 2 cardiovascular risk factors (smoking, high blood pressure, high cholesterol, diabetes, overweight, age (>55 for men, >65 for women), family history of stroke).
- Left middle cerebral artery ischemic stroke with at least 6 month chronicity
- Right upper extremity weakness with a Rasch-modified Fugl-Meyer upper extremity score of 20 to 50
- Ability to voluntarily flex the affected elbow and shoulder from 10-75% of the normal range
Key exclusion criteria (11 listed)
- Primary intracerebral hematoma or subarachnoid hemorrhage
- Bi-hemispheric ischemic strokes
- History of prior right-sided stroke or old infarct demonstrated on the CT or MRI or documented in medical records
- Other concomitant neurological disorders affecting upper extremity motor function
- Documented history of dementia before or after stroke
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 |
|---|---|---|
| Rasch modified version of the Fugl-Meyer Motor assessmentAll participants will receive a comprehensive clinical assessment of motor function including the Rasch modified version of the Fugl-Meyer Motor assessment and a kinematic assessment of unimanual and bimanual movements using a 45 sensor 3D active marker based motion capture system. The three primary measures investigated in the kinematics include: 1) movement efficiency, 2) movement smoothness, and 3) motor compensation. | Diagnostic test | Healthy Controls, Stroke Participants |
| Anatomical image acquisitionHigh-resolution structural scans will be obtained using an inversion recovery 3D spoiled gradient echo (3DSPGR) sequence using a matrix size of 256 x 256, field of view of 24 cm, section thickness of 1.5 mm with no gap between sections, and 128 slices, giving an in-plane resolution of 0.94 mm. This sequence will be used for anatomic overlays of the functional data and for spatial normalization to a standard atlas. | Diagnostic test | Healthy Controls, Stroke Participants |
| Functional MRI task and acquisitionBriefly, patients will be given two pressure-sensitive bulbs (one to be held in each hand and fastened lightly to their wrists with Velcro such that they do not drop it during the scan. During two 2½ minute runs they will be prompted to squeeze the bulb in either their affected or unaffected hand in blocks of 15 seconds. These blocks will be interspersed with blocks of rest. The pressure from the bulbs will be digitally recorded and quantified offline in order to: 1) verify that the patient was squeezing the ball, and 2) assess the presence of 'mirror movements' from the opposing hand that may inform the imaging results regarding loss of laterality). | Diagnostic test | Healthy Controls, Stroke Participants |
Primary outcome
Compare the ratio of gluatamte and gaba concentrations within the contralesional primary motor cortex
Time frame: Through study completion, an average of two weeks
Using spectroscopy investigators will determine if the ratio of glutamate/GABA is higher in stroke patients than controls. Furthermore, in healthy controls prepulse inhibition will be positively correlated with the concentration of GABA, and prepulse facilitation will be positively correlated with the concentration of glutamate. Although we expect this relationship to be true in both the controls and the stroke patients, variation from this pattern in the stroke patients would suggest that there is another factor beyond simple within-hemisphere measurements that is affecting the contralesional cortex activity.
1 secondary outcome
Quantify the relationship between neural activity and motor performance using the Rasch modified version of the Fugl-Meyer motor assessment battery to acquire three aspects of motor performance for all individuals in both groups.
Time frame: Through study completion, an average of two weeks
Results and safety
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 23 Jul 2019.
- Individual participant dataSharing planned: Yes. Yes The data from the primary outcome measurement will be shared via manuscripts and after study completion by request to the Principal Investigator
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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.
Colleen A Hanlon, PhD principal investigator
Medical University of South Carolina
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Early Phase 1 study testing Rasch modified version of the Fugl-Meyer Motor assessment, Anatomical image acquisition and Functional MRI task and acquisition in people with Stroke and Motor Cortex; Lesion, run by Medical University of South Carolina 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 6 inclusion and 11 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: finished, as of the sponsor's last update on 23 Jul 2019. 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.
What does this phase mean?
Early Phase 1 (sometimes called Phase 0) studies give a very small amount of a treatment to a few people, mainly to see how the body handles it.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
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?
Compare the ratio of gluatamte and gaba concentrations within the contralesional primary motor cortex (time frame: Through study completion, an average of two weeks). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
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 23 Jul 2019.