Cerebrovascular DisorderNCT03366129
Blood-Brain Barrier Disruption in People With White Matter Hyperintensities Who Have Had a Stroke
An observational study of Cerebrovascular Disorder and Stroke, run by National Institute of Neurological Disorders and Stroke (NINDS) at 3 sites in United States.
Trial summary
Background: A stroke occurs when not enough blood reaches the brain. Sometimes stroke causes changes in certain brain matter. This is called white matter hyperintensity (WMH) and can lead to mental decline. But not all WMH is caused by stroke. Not all people with WMH experience mental decline. Read more about this study
- Who is it for?
- Ages 18 to 99 years
- Conditions the study is for
- Cerebrovascular Disorder, Stroke, Aging
- How many people
- 81 participants
- Where
- 3 sitesUnited States
- Study dates
- 6 Sep 2018to 18 Dec 2023
- 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 99 years
- All sexes
- No healthy volunteers
- Adult, Older adult
Study population: Stroke patients will be eligible for this study if their MRI shows evidence of confluent WMH on FLAIR imaging (Fazekas score 2 or greater), obtain a MoCA score greater than 13, and have no other diagnosis to explain the finding (e.g. multiple sclerosis). The NIH stroke service currently evaluates 600 patients a year with MRI. Approximately 20% have confluent WMH on their FLAIR MRI and would meet the inclusion criteria for this study. Thus, the cohort for this study will be recruited from the population evaluated by the NIH stroke service.
Who may be able to join
- Age greater than or equal to 18
- Have been evaluated for stroke-like symptoms or have radiographic evidence of stroke on an MRI scan.
- Is willing to return to one of the two study sites for serial study visits.
- Is willing to appoint a Durable Power of Attorney (DPA) for NIH research.
- Is willing to provide written informed consent prior to participation OR a qualifying LAR will provide consent and the subject is able to provide assent.
Who cannot join
- An individual who meets any of the following criteria will be excluded from this study:
- Medical contraindications for MRI (e.g., any non-organic implant or other device such as a cardiac pacemaker or infusion pump or other metallic implants, objects, or body piercings that are not MRI-compatible or cannot be removed)
- Psychological contraindications for MRI (e.g., claustrophobia), to be assessed at the time the medical history is collected
- If unable to lie comfortably on their back for up to 1 hour.
- Contraindication to gadolinium (pregnant or nursing, previous allergic reaction, renal insufficiency)
- Known diagnosis that is thought to be the cause of their WMH (e.g. multiple sclerosis) other than chronic cerebrovascular disease, cerebral autosomal dominant arteriopathy with subcortical infarcts (CADASIL), or migraine.
Show all 11Show fewer
- Clinically significant medical or neurological disorders that might expose the patient to undue risk of harm, confound study outcomes or prevent the participant from completing the study; examples of such conditions include but are not limited to respiratory compromise, cardiovascular instability or cerebral edema.
- History of an ongoing seizure disorder, structural brain abnormality or nonvascular brain injury.
- Unlikely to be released from the hospital following the qualifying event or has severe disability preventing ambulation or verbal communication.
- Known malignant disease or other chronic illness with poor 5-year prognosis other than dementia.
- Attaining a six-item screener score less than 4, during screening.
Trial locations and contacts
3 sites in 1 country.
United States3 sites
Suburban Hospital - Johns Hopkins
Bethesda, Maryland, 20814
National Institutes of Health Clinical Center
Bethesda, Maryland, 20892
MedStar Washington Hospital Center
Washington D.C., District of Columbia, 20010
About this study
Official title: The Natural History of Blood-Brain Barrier Disruption in Stroke Patients With White Matter Hyperintensities (A Cohort Study)
Background:
A stroke occurs when not enough blood reaches the brain. Sometimes stroke causes changes in certain brain matter. This is called white matter hyperintensity (WMH) and can lead to mental decline. But not all WMH is caused by stroke. Not all people with WMH experience mental decline. Researchers want to learn more about WMH. They want to see if it is related to disruptions in the blood-brain barrier.
Read more
Objective:
To better understand the how blood-brain barrier disruption is related to white matter hyperintensities.
Eligibility:
Adults at least 18 years old who have been admitted to a study site with stroke-like symptoms
Design:
Participants will be screened with an MRI scan and cognitive tests.
Participants will have 11 visits over 6 years. Each visit will be 3-4 hours.
At each visit, participants will:
Update their medical history
Have a thin plastic tube (catheter) inserted into an arm vein by needle
Have an MRI. The scanner is a metal cylinder in a strong magnetic field. Participants will lie on a table that slides in and out of the cylinder. Participants will be in the scanner about 60 minutes, lying still for up to 20 minutes at a time. They will get earmuffs for loud sounds.
Have a dye injected through the catheter during the MRI
Have tests of movement, language, and cognition
Some participants will have an extra visit for an MRI in a stronger scanner (7T MRI).
Participation for some participants will be authorized by their legal representative.
Read the detailed description
Objective: To follow a cohort of stroke patients with white matter hyperintensities (WMH), using MRI, and thereby track the natural history of changes in blood-brain barrier (BBB) disruption. By establishing a better understanding of the relationship between the presence of BBB disruption and WMH progression, we hope to identify BBB permeability on MRI as a biomarker for disease pathogenesis, disease activity, and disease progression.
Study Population: Stroke patients will be eligible for this study if their MRI shows evidence of confluent WMH on FLAIR imaging (Fazekas score 2 or greater), obtain a six-item screener score greater than 3, and have no other diagnosis to explain the finding (e.g. multiple sclerosis). The NIH stroke service currently evaluates 600 patients a year with MRI. Approximately 20% have confluent WMH on their FLAIR MRI and would meet the inclusion criteria for this study. Thus, the cohort for this study will be recruited from the population evaluated by the NIH stroke service.
Design: Patients with a clinical or radiographic history of stroke will be eligible for enrollment. Enrolled subjects who meet the inclusion/exclusion criteria will be followed serially with MRI. Research procedures will consist of an MRI, interval history and cognitive/clinical scaling. Research procedures will occur every 3 months for the first year, every 6 months for the second year, and then yearly thereafter for a total of 6 years or untill the study has ended.
Outcome measures: Using a previously described and independently validated method, BBB permeability will be assessed at each research time point as will WMH burden. The presence of BBB will be compared with progression of WMH into normal appearing white matter (NAWM). The primary outcome is the relationship between BBB disruption and WMH progression. It is postulated that BBB disruption in the NAWM will be associated with progression of the WMH. Secondary outcomes will examine the spatial relationship between BBB disruption and WMH progression and changes in cognitive scaling. Additionally, other exploratory MRI biomarkers for disease progression will be examined (e.g. susceptibility weighted imaging with 7T MRI to examine regions of known BBB disruption).
- Conditions
- Cerebrovascular Disorder, Stroke, Aging
- Keywords
- CEREBROVASCULAR DISEASE, Vascular Cognitive Impairment, Stroke, Permeability Imaging, Natural History
- Medical subject headings
- Cerebrovascular Disorders, Stroke
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
| Study group | Role | What they receive |
|---|---|---|
| Cohort | Stroke patients with white matter hyperintensities (WMH) |
What is being measured
The primary outcome is the main question the study is designed to answer.
The primary outcome is the relationship between BBB disruption and WMH progression. It is postulated that BBB disruption in the NAWM will be associated with progression of the WMH.
Using a previously described and independently validated method, BBB permeability will be assessed at each research time point as will WMH burden. The presence of BBB will be compared with progression of WMH into normal appearing white matter (NAWM).
Measured: Assessed at each research time point
Secondary outcomes (1)
Secondary outcomes will examine the spatial relationship between BBB disruption and WMH progression and changes in cognitive scaling.
(1) To examine the spatial relation between the location of BBB disruption and the location of subsequent progression of NAWM into WMH (2) To examine the relationship between clinical risk factors, demographics, routine lab results, and clinical scales of neurologic deficit, functional status, and cognitive function with measures of BBB disruption and WMH. (3) To test several exploratory imaging biomarkers for BBB disruption and WMH. (4) To explore how susceptibility weighted imaging (SWI) on 7T MRI may be used to image BBB disruption and disease activity.37 (5) To identify potential subjects for research studies on cerebrovascular diseases.(6) To study the role of free water (FW) measured on DTI in the progression of WMH
Measured: Assessed at each research time point
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted8 Dec 2017
- Study start6 Sep 2018
- Primary completion18 Dec 2023
- Study completion18 Dec 2023
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (2)Papers the sponsor has linked to this study.
- Other trials for Cerebrovascular DisorderStudies of the same condition, open and under way.
- More trials run by National Institute of Neurological Disorders and Stroke (NINDS)The 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
- Observational
- Observational model
- Cohort
- Time perspective
- Prospective
- Enrolment
- 81 participants (actual)
Sponsor and investigators
- Sponsor type
- US National Institutes of Health
- Responsible party
- Sponsor
- Investigators
- Clinton B Wright, M.D., Principal investigator, National Institute of Neurological Disorders and Stroke (NINDS)
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT03366129
- Sponsor's protocol ID
- 180020
- Other IDs
- 18-N-0020
- Status last verified
- 15 Jun 2026
- First submitted
- 7 Dec 2017
- Last updated
- 28 Sep 2026
- Results posted
- No
- FDA-regulated drug
- No
- FDA-regulated device
- No
Publications
Leigh R, Jen SS, Varma DD, Hillis AE, Barker PB. Arrival time correction for dynamic susceptibility contrast MR permeability imaging in stroke patients. PLoS One. 2012;7(12):e52656. doi: 10.1371/journal.pone.0052656. Epub 2012 Dec 20.
PubMed 23285132Kern KC, Zagzoug MS, Gottesman RF, Wright CB, Leigh R. Blood-brain barrier disruption and increased free water are associated with worse cognitive performance in patients with chronic cerebrovascular disease. Neuroimage Clin. 2024;44:103706. doi: 10.1016/j.nicl.2024.103706. Epub 2024 Nov 13.
PubMed 39551018
Study at a glance
From the registry record, last updated by the sponsor on 28 Sep 2026. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- The Natural History of Blood-Brain Barrier Disruption in Stroke Patients With White Matter Hyperintensities (A Cohort Study)
- ClinicalTrials.gov ID
- NCT03366129
- Acronym / sponsor ID
- 180020
- Conditions
- Cerebrovascular Disorder, Stroke, Aging
- Keywords
- CEREBROVASCULAR DISEASE, Vascular Cognitive Impairment, Stroke, Permeability Imaging, Natural History
- Study type
- Observational
- Recruitment status
- Completed
- Enrolment
- 81 participants (actual)
- Lead sponsor
- National Institute of Neurological Disorders and Stroke (NINDS)US National Institutes of Health
- Study start
- 6 Sep 2018 (actual)
- Primary completion
- 18 Dec 2023 (actual)
- Study completion
- 18 Dec 2023 (actual)
- First posted
- 8 Dec 2017 (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.
Background:
A stroke occurs when not enough blood reaches the brain. Sometimes stroke causes changes in certain brain matter. This is called white matter hyperintensity (WMH) and can lead to mental decline. But not all WMH is caused by stroke. Not all people with WMH experience mental decline. Researchers want to learn more about WMH. They want to see if it is related to disruptions in the blood-brain barrier.
Objective:
To better understand the how blood-brain barrier disruption is related to white matter hyperintensities.
Eligibility:
Adults at least 18 years old who have been admitted to a study site with stroke-like symptoms
Design:
Participants will be screened with an MRI scan and cognitive tests.
Participants will have 11 visits over 6 years. Each visit will be 3-4 hours.
At each visit, participants will:
Update their medical history
Have a thin plastic tube (catheter) inserted into an arm vein by needle
Have an MRI. The scanner is a metal cylinder in a strong magnetic field. Participants will lie on a table that slides in and out of the cylinder. Participants will be in the scanner about 60 minutes, lying still for up to 20 minutes at a time. They will get earmuffs for loud sounds.
Have a dye injected through the catheter during the MRI
Have tests of movement, language, and cognition
Some participants will have an extra visit for an MRI in a stronger scanner (7T MRI).
Participation for some participants will be authorized by their legal representative.
Detailed description
Objective: To follow a cohort of stroke patients with white matter hyperintensities (WMH), using MRI, and thereby track the natural history of changes in blood-brain barrier (BBB) disruption. By establishing a better understanding of the relationship between the presence of BBB disruption and WMH progression, we hope to identify BBB permeability on MRI as a biomarker for disease pathogenesis, disease activity, and disease progression.
Study Population: Stroke patients will be eligible for this study if their MRI shows evidence of confluent WMH on FLAIR imaging (Fazekas score 2 or greater), obtain a six-item screener score greater than 3, and have no other diagnosis to explain the finding (e.g. multiple sclerosis). The NIH stroke service currently evaluates 600 patients a year with MRI. Approximately 20% have confluent WMH on their FLAIR MRI and would meet the inclusion criteria for this study. Thus, the cohort for this study will be recruited from the population evaluated by the NIH stroke service.
Design: Patients with a clinical or radiographic history of stroke will be eligible for enrollment. Enrolled subjects who meet the inclusion/exclusion criteria will be followed serially with MRI. Research procedures will consist of an MRI, interval history and cognitive/clinical scaling. Research procedures will occur every 3 months for the first year, every 6 months for the second year, and then yearly thereafter for a total of 6 years or untill the study has ended.
Outcome measures: Using a previously described and independently validated method, BBB permeability will be assessed at each research time point as will WMH burden. The presence of BBB will be compared with progression of WMH into normal appearing white matter (NAWM). The primary outcome is the relationship between BBB disruption and WMH progression. It is postulated that BBB disruption in the NAWM will be associated with progression of the WMH. Secondary outcomes will examine the spatial relationship between BBB disruption and WMH progression and changes in cognitive scaling. Additionally, other exploratory MRI biomarkers for disease progression will be examined (e.g. susceptibility weighted imaging with 7T MRI to examine regions of known BBB disruption).
Study design
- Observational model
- Cohort
- Time perspective
- Prospective
- Number of arms
- 1
| Arm | Type | Receives |
|---|---|---|
| Cohort | – | –Stroke patients with white matter hyperintensities (WMH) |
Who may qualify
- Ages
- 18 to 99 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
- Study population
- Stroke patients will be eligible for this study if their MRI shows evidence of confluent WMH on FLAIR imaging (Fazekas score 2 or greater), obtain a MoCA score greater than 13, and have no other diagnosis to explain the finding (e.g. multiple sclerosis). The NIH stroke service currently evaluates 600 patients a year with MRI. Approximately 20% have confluent WMH on their FLAIR MRI and would meet the inclusion criteria for this study. Thus, the cohort for this study will be recruited from the population evaluated by the NIH stroke service.
Key inclusion criteria (5 listed)
Key exclusion criteria (11 listed)
- Medical contraindications for MRI (e.g., any non-organic implant or other device such as a cardiac pacemaker or infusion pump or other metallic implants, objects, or body piercings that are not MRI-compatible or cannot be removed)
- Psychological contraindications for MRI (e.g., claustrophobia), to be assessed at the time the medical history is collected
- If unable to lie comfortably on their back for up to 1 hour.
- Contraindication to gadolinium (pregnant or nursing, previous allergic reaction, renal insufficiency)
- Known diagnosis that is thought to be the cause of their WMH (e.g. multiple sclerosis) other than chronic cerebrovascular disease, cerebral autosomal dominant arteriopathy with subcortical infarcts (CADASIL), or migraine.
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Primary outcome
The primary outcome is the relationship between BBB disruption and WMH progression. It is postulated that BBB disruption in the NAWM will be associated with progression of the WMH.
Time frame: Assessed at each research time point
Using a previously described and independently validated method, BBB permeability will be assessed at each research time point as will WMH burden. The presence of BBB will be compared with progression of WMH into normal appearing white matter (NAWM).
1 secondary outcome
Secondary outcomes will examine the spatial relationship between BBB disruption and WMH progression and changes in cognitive scaling.
Time frame: Assessed at each research time point
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 28 Sep 2026.
- Background: PubMed 23285132Leigh R, Jen SS, Varma DD, Hillis AE, Barker PB. Arrival time correction for dynamic susceptibility contrast MR permeability imaging in stroke patients. PLoS One. 2012;7(12):e52656. doi: 10.1371/journal.pone.0052656. Epub 2012 Dec 20.
- Derived from this study: PubMed 39551018Kern KC, Zagzoug MS, Gottesman RF, Wright CB, Leigh R. Blood-brain barrier disruption and increased free water are associated with worse cognitive performance in patients with chronic cerebrovascular disease. Neuroimage Clin. 2024;44:103706. doi: 10.1016/j.nicl.2024.103706. Epub 2024 Nov 13.
- NIH Clinical Center Detailed Web PageLink provided by the sponsor.
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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.
Clinton B Wright, M.D. principal investigator
National Institute of Neurological Disorders and Stroke (NINDS)
3 sites in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
An observational study of Cerebrovascular Disorder and Stroke, run by National Institute of Neurological Disorders and Stroke (NINDS) 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 5 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 28 Sep 2026. 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?
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?
The primary outcome is the relationship between BBB disruption and WMH progression. It is postulated that BBB disruption in the NAWM will be associated with progression of the WMH. (time frame: Assessed at each research time point). 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 NCT03366129, which also lists 2 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 28 Sep 2026.