Left-Hemisphere StrokeNCT03845686
Brain Markers Predicting Reading Recovery After Stroke
An observational study of Left-Hemisphere Stroke, run by Kessler Foundation at 1 site in United States.
Trial summary
For millions of stroke survivors acquired reading deficits represent a significant handicap preventing them from returning to work or continuing their education. The goal of the proposed research is to investigate what brain mechanisms enable recovery of impaired reading. Read more about this study
- Who is it for?
- Ages 18 to 100 years
- Conditions the study is for
- Left-Hemisphere Stroke
- What is being tested?
- Perfusion functional Magnetic Resonance Imaging (perfusion fMRI)
- How many people
- 26 participants
- Where
- 1 siteUnited States
- Study dates
- 4 Apr 2018to 1 Jul 2021
- Phase
- Observational
- 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 18 to 100 years
- All sexes
- No healthy volunteers
- Adult, Older adult
Study population: 34 participants with first-ever left-brain stroke
Who may be able to join
- age >18 years
- right-handed
- fluent and literate in English prior to stroke
- no prior neurological disorders or clinical stroke event
- <4 weeks post-stroke
- ability to undergo an MRI and complete study tasks
- presence of reading deficits
Who cannot join
- participants with severe aphasia resulting in severe language deficits and inability to consent
- participants with very large lesions resulting in severe cognitive deficits and inability to consent
Trial locations and contacts
1 site in 1 country.
About this study
For millions of stroke survivors acquired reading deficits represent a significant handicap preventing them from returning to work or continuing their education. The goal of the proposed research is to investigate what brain mechanisms enable recovery of impaired reading. To achieve this goal, the project will directly measure changes in brain perfusion (blood flow) and activation among recovering stroke survivors using a neuroimaging technique called perfusion fMRI (functional Magnetic Resonance Imaging). The project will test if re-perfusion (return of circulation) and re-appearance of reading-related brain activity in the left-brain network for reading is associated with recovery. The ability to predict recovery from neuroimaging has tremendous value in rehabilitation for generating prognoses. It may also dramatically improve the quality of research evaluation for novel, targeted interventions such as noninvasive brain stimulation or pharmacologic therapies.
Read the detailed description
There is a fundamental gap in understanding the neuro-behavioral time-course of reading recovery following stroke. It is not known whether recovery of reading is associated with improved blood circulation and neural activity of the peri-infarct area, or whether circulation in the unaffected, contralateral brain areas contributes to functional recovery. Continued existence of this gap represents an important problem because, until it is filled, knowledge about optimal timing and targets for restorative therapies to improve reading will remain out of reach. The long-term goal is to develop clinical prognostic and therapeutic tools to improve reading limitations. The overall objective of this project is to characterize the neural mechanisms of recovery from stroke-induced reading impairments. The central hypothesis of this study is that subacute-to-chronic recovery of reading ability is potentiated by reperfusion (improved blood flow) of the left reading network. Reperfusion promotes the return of neural activity and supports behavioral recovery. In contrast, increased perfusion of the right brain areas represents a maladaptive response and is associated with worse chronic reading ability. This hypothesis has been formulated on the basis of preliminary data. The rationale for the proposed research is that once the neural recovery from stroke-induced reading impairments is characterized, clinicians will be able to predict individual recovery potential and select appropriate rehabilitation goals. Guided by strong preliminary data, this hypothesis will be tested by pursuing two specific aims: 1) Determine whether post-stroke changes in cerebral blood flow predict recovery of reading ability; and 2) Determine whether increased baseline perfusion of the left reading network is paralleled by greater reading-related neural activation. Under the first aim, perfusion in the peri-infarct tissue, left reading network, and homologous right brain areas will be examined among left stroke patients with reading impairments. A non-invasive measure of perfusion (Arterial Spin Labeling, ASL MRI) will be applied longitudinally: <4 weeks post-stroke (sub-acute) and >3 months post-stroke (chronic) to test if increased perfusion of the left reading network is coupled with an improvement of reading accuracy. Under the second aim, reading-induced brain activity will be recorded in the same group of patients using perfusion-based functional MRI. The effect of task-related neural activity on recovery will be separated from the effect of cerebral blood flow by statistically controlling for baseline circulation and by modeling independent contributions of perfusion and BOLD (Blood Oxygen Level Dependent) signals in order to estimate cerebral oxygen consumption rate, which is directly related to neural activity. The conceptual innovation of this study is that it offers the opportunity to examine reading recovery as distinct from other functions. The methodological innovation is in using simultaneously-acquired perfusion and BOLD signals, helping to measure longitudinal changes in circulation and neural activity with unprecedented precision. The proposed research is significant because it can help greatly improve the effectiveness of post-stroke rehabilitation.
- Conditions
- Left-Hemisphere Stroke
- Being tested
- Perfusion functional Magnetic Resonance Imaging (perfusion fMRI)
- Keywords
- stroke, reading, fMRI, perfusion, activation, BOLD, recovery, subacute, chronic
- Medical subject headings
- Stroke, Bronchiolitis Obliterans Syndrome
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Perfusion functional Magnetic Resonance Imaging (perfusion fMRI)Diagnostic test
The goal of this test is to measure brain activity during subacute and chronic post-stroke period using a widely available non-invasive neuroimaging tool - functional Magnetic Resonance Imaging (fMRI). Because fMRI relies in part on cerebral blood flow, which is altered in stroke, measuring longitudinal changes in neural activity with fMRI requires that we control for concomitant changes in blood circulation. To do this, we will employ a novel dual-echo perfusion fMRI sequence, which will allow us to separately estimate neural and vascular contributions to fMRI.
| Study group | Role | What they receive |
|---|---|---|
| Subacute Stroke Sample | Participants with first-ever left-brain stroke, < 4 weeks post stroke, age >18 years, right-handed, fluent and literate in English prior to stroke, no prior neurological disorders or clinical stroke event, <4 weeks post-stroke; able to undergo an MRI and complete study tasks, and presence of reading deficits. Receives: Diagnostic Test: Perfusion functional Magnetic Resonance Imaging (perfusion fMRI) | |
| Chronic Stroke Sample | The same group of participants examined in the chronic post-stroke period (>3 months post-stroke) Receives: Diagnostic Test: Perfusion functional Magnetic Resonance Imaging (perfusion fMRI) |
What is being measured
The primary outcome is the main question the study is designed to answer.
Reading Aloud Accuracy - subacute
Percent correct of single words read aloud
Measured: within 1 week of study enrollment
Reading Aloud Accuracy - chronic
Percent correct of single words read aloud
Measured: 3 months after study enrollment
Phonology Task Accuracy - subacute
2-alternative forced choice task of pseudoword rhyming
Measured: within 1 week of enrollment
Phonology Task Accuracy - chronic
2-alternative forced choice task of pseudoword rhyming
Measured: 3 months after study enrollment
Semantics Task Accuracy - subacute
2-alternative forced choice task of picture matching
Measured: within 1 week of enrollment
Semantics Task Accuracy - chronic
2-alternative forced choice task of picture matching
Measured: 3 months after study enrollment
Orthography Task Accuracy - subacute
2 alternative forced choice between a correctly spelled word and a phonological foil
Measured: within 1 week of enrollment
Orthography Task Accuracy - chronic
2 alternative forced choice between a correctly spelled word and a phonological foil
Measured: 3 months after study enrollment
Perfusion MRI - subacute
Subacute cerebral blood flow (CBF) in peri-infarct tissue, left reading network, and right homologous areas
Measured: within 1 week of enrollment
Perfusion MRI - chronic
Subacute-to-chronic change of CBF in peri-infarct tissue, left reading network, and right homologous areas
Measured: 3 months after enrollment
Functional MRI - subacute
Brain activation for reading words and nonwords; task-induced change in oxygen consumption
Measured: within 1 week of enrollment
Functional MRI - chronic
Subacute-to-chronic change of brain activation for reading words and pseudowords; longitudinal and task-induced change in oxygen consumption
Measured: 3 months after enrollment
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted19 Feb 2019
- Study start4 Apr 2018
- Primary completion1 Jul 2021
- Study completion1 Jul 2021
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Left-Hemisphere 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
- Observational
- Observational model
- Cohort
- Time perspective
- Prospective
- Enrolment
- 26 participants (actual)
Sponsor and investigators
- Lead sponsor
- Kessler Foundation
- Sponsor type
- University, hospital or other
- Collaborators
- Rutgers University, National Center for Medical Rehabilitation Research (NCMRR)
- Responsible party
- Principal investigator, Olga Boukrina, Kessler Foundation
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT03845686
- Sponsor's protocol ID
- R-784-13
- Status last verified
- Apr 2021
- First submitted
- 15 Feb 2019
- Last updated
- 31 Aug 2021
- Results posted
- No
- Data monitoring committee
- No
- FDA-regulated drug
- No
- FDA-regulated device
- No
- Individual data sharing
- Yes: Data generated in this project may be shared in accordance with the NIH and Kessler Foundation policies, as well as the Notice of Privacy of Practices signed by each participant in the study. In case data is shared, it will be de-identified, such that no link can be made to the individual participant. Data may be shared upon request after the acceptance for publication of the main findings of the study. Publication of findings will occur during the project, if appropriate, or at the conclusion of the project, consistently with the typical scientific process. Access to methodology and software tools generated in the course of the project will be granted for educational, research, and non-profit purposes. Sharing of such study resources will be provided via web-based applications (e.g., GitHub), as appropriate.
Study at a glance
From the registry record, last updated by the sponsor on 31 Aug 2021. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Brain Markers Predicting Reading Recovery After Stroke
- ClinicalTrials.gov ID
- NCT03845686
- Acronym / sponsor ID
- R-784-13
- Conditions
- Left-Hemisphere Stroke
- Keywords
- stroke, reading, fMRI, perfusion, activation, BOLD, recovery, subacute
- Study type
- Observational
- Recruitment status
- Completed
- Enrolment
- 26 participants (actual)
- Lead sponsor
- Kessler FoundationUniversity, hospital or other
- Collaborators
- Rutgers University, National Center for Medical Rehabilitation Research (NCMRR)
- Study start
- 4 Apr 2018 (actual)
- Primary completion
- 1 Jul 2021 (actual)
- Study completion
- 1 Jul 2021 (actual)
- First posted
- 19 Feb 2019 (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.
For millions of stroke survivors acquired reading deficits represent a significant handicap preventing them from returning to work or continuing their education. The goal of the proposed research is to investigate what brain mechanisms enable recovery of impaired reading. To achieve this goal, the project will directly measure changes in brain perfusion (blood flow) and activation among recovering stroke survivors using a neuroimaging technique called perfusion fMRI (functional Magnetic Resonance Imaging). The project will test if re-perfusion (return of circulation) and re-appearance of reading-related brain activity in the left-brain network for reading is associated with recovery. The ability to predict recovery from neuroimaging has tremendous value in rehabilitation for generating prognoses. It may also dramatically improve the quality of research evaluation for novel, targeted interventions such as noninvasive brain stimulation or pharmacologic therapies.
Detailed description
There is a fundamental gap in understanding the neuro-behavioral time-course of reading recovery following stroke. It is not known whether recovery of reading is associated with improved blood circulation and neural activity of the peri-infarct area, or whether circulation in the unaffected, contralateral brain areas contributes to functional recovery. Continued existence of this gap represents an important problem because, until it is filled, knowledge about optimal timing and targets for restorative therapies to improve reading will remain out of reach. The long-term goal is to develop clinical prognostic and therapeutic tools to improve reading limitations. The overall objective of this project is to characterize the neural mechanisms of recovery from stroke-induced reading impairments. The central hypothesis of this study is that subacute-to-chronic recovery of reading ability is potentiated by reperfusion (improved blood flow) of the left reading network. Reperfusion promotes the return of neural activity and supports behavioral recovery. In contrast, increased perfusion of the right brain areas represents a maladaptive response and is associated with worse chronic reading ability. This hypothesis has been formulated on the basis of preliminary data. The rationale for the proposed research is that once the neural recovery from stroke-induced reading impairments is characterized, clinicians will be able to predict individual recovery potential and select appropriate rehabilitation goals. Guided by strong preliminary data, this hypothesis will be tested by pursuing two specific aims: 1) Determine whether post-stroke changes in cerebral blood flow predict recovery of reading ability; and 2) Determine whether increased baseline perfusion of the left reading network is paralleled by greater reading-related neural activation. Under the first aim, perfusion in the peri-infarct tissue, left reading network, and homologous right brain areas will be examined among left stroke patients with reading impairments. A non-invasive measure of perfusion (Arterial Spin Labeling, ASL MRI) will be applied longitudinally: <4 weeks post-stroke (sub-acute) and >3 months post-stroke (chronic) to test if increased perfusion of the left reading network is coupled with an improvement of reading accuracy. Under the second aim, reading-induced brain activity will be recorded in the same group of patients using perfusion-based functional MRI. The effect of task-related neural activity on recovery will be separated from the effect of cerebral blood flow by statistically controlling for baseline circulation and by modeling independent contributions of perfusion and BOLD (Blood Oxygen Level Dependent) signals in order to estimate cerebral oxygen consumption rate, which is directly related to neural activity. The conceptual innovation of this study is that it offers the opportunity to examine reading recovery as distinct from other functions. The methodological innovation is in using simultaneously-acquired perfusion and BOLD signals, helping to measure longitudinal changes in circulation and neural activity with unprecedented precision. The proposed research is significant because it can help greatly improve the effectiveness of post-stroke rehabilitation.
Study design
- Observational model
- Cohort
- Time perspective
- Prospective
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| Subacute Stroke Sample | – | Diagnostic Test: Perfusion functional Magnetic Resonance Imaging (perfusion fMRI)Participants with first-ever left-brain stroke, < 4 weeks post stroke, age >18 years, right-handed, fluent and literate in English prior to stroke, no prior neurological disorders or clinical stroke event, <4 weeks post-stroke; able to undergo an MRI and complete study tasks, and presence of reading deficits. |
| Chronic Stroke Sample | – | Diagnostic Test: Perfusion functional Magnetic Resonance Imaging (perfusion fMRI)The same group of participants examined in the chronic post-stroke period (>3 months post-stroke) |
Who may qualify
- Ages
- 18 to 100 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
- Study population
- 34 participants with first-ever left-brain stroke
Key inclusion criteria (7 listed)
- age >18 years
- right-handed
- fluent and literate in English prior to stroke
- no prior neurological disorders or clinical stroke event
- <4 weeks post-stroke
Key exclusion criteria (2 listed)
- participants with severe aphasia resulting in severe language deficits and inability to consent
- participants with very large lesions resulting in severe cognitive deficits and inability to consent
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 |
|---|---|---|
| Perfusion functional Magnetic Resonance Imaging (perfusion fMRI)The goal of this test is to measure brain activity during subacute and chronic post-stroke period using a widely available non-invasive neuroimaging tool - functional Magnetic Resonance Imaging (fMRI). Because fMRI relies in part on cerebral blood flow, which is altered in stroke, measuring longitudinal changes in neural activity with fMRI requires that we control for concomitant changes in blood circulation. To do this, we will employ a novel dual-echo perfusion fMRI sequence, which will allow us to separately estimate neural and vascular contributions to fMRI. | Diagnostic test | Chronic Stroke Sample, Subacute Stroke Sample |
Primary outcome
Reading Aloud Accuracy - subacute
Time frame: within 1 week of study enrollment
Percent correct of single words read aloud
Reading Aloud Accuracy - chronic
Time frame: 3 months after study enrollment
Percent correct of single words read aloud
Phonology Task Accuracy - subacute
Time frame: within 1 week of enrollment
2-alternative forced choice task of pseudoword rhyming
Phonology Task Accuracy - chronic
Time frame: 3 months after study enrollment
2-alternative forced choice task of pseudoword rhyming
Semantics Task Accuracy - subacute
Time frame: within 1 week of enrollment
2-alternative forced choice task of picture matching
Semantics Task Accuracy - chronic
Time frame: 3 months after study enrollment
2-alternative forced choice task of picture matching
Orthography Task Accuracy - subacute
Time frame: within 1 week of enrollment
2 alternative forced choice between a correctly spelled word and a phonological foil
Orthography Task Accuracy - chronic
Time frame: 3 months after study enrollment
2 alternative forced choice between a correctly spelled word and a phonological foil
Perfusion MRI - subacute
Time frame: within 1 week of enrollment
Subacute cerebral blood flow (CBF) in peri-infarct tissue, left reading network, and right homologous areas
Perfusion MRI - chronic
Time frame: 3 months after enrollment
Subacute-to-chronic change of CBF in peri-infarct tissue, left reading network, and right homologous areas
Functional MRI - subacute
Time frame: within 1 week of enrollment
Brain activation for reading words and nonwords; task-induced change in oxygen consumption
Functional MRI - chronic
Time frame: 3 months after enrollment
Subacute-to-chronic change of brain activation for reading words and pseudowords; longitudinal and task-induced change in oxygen consumption
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 31 Aug 2021.
- Individual participant dataSharing planned: Yes. Data generated in this project may be shared in accordance with the NIH and Kessler Foundation policies, as well as the Notice of Privacy of Practices signed by each participant in the study. In case data is shared, it will be de-identified, such that no link can be made to the individual participant. Data may be shared upon request after the acceptance for publication of the main findings of the study. Publication of findings will occur during the project, if appropriate, or at the conclusion of the project, consistently with the typical scientific process. Access to methodology and software tools generated in the course of the project will be granted for educational, research, and non-profit purposes. Sharing of such study resources will be provided via web-based applications (e.g., GitHub), as appropriate.
Related trials for Left-Hemisphere Stroke
Enrolling by invitation
Evaluation of an Adaptive Neurotechnology Based on Motor Imagery in Patients Who Suffered a Left Hemisphere Stroke
Stroke, Brain Computer Interface
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.
The record lists no contact. Use the official record to reach the sponsor.
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
An observational study of Left-Hemisphere Stroke, run by Kessler Foundation 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 7 inclusion and 2 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 31 Aug 2021. 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?
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?
Reading Aloud Accuracy - subacute (time frame: within 1 week of study enrollment). The study lists 12 primary outcomes in all. 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 31 Aug 2021.