Blood-Brain Barrier Disruption in People With White Matter Hyperintensities Who Have Had a Stroke
- Conditions
- StrokeAgingCerebrovascular Disorder
- Registration Number
- NCT03366129
- Brief 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. 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.
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- 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).
Recruitment & Eligibility
- Status
- COMPLETED
- Sex
- All
- Target Recruitment
- 70
Not provided
Not provided
Study & Design
- Study Type
- OBSERVATIONAL
- Study Design
- Not specified
- Primary Outcome Measures
Name Time Method 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. 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).
- Secondary Outcome Measures
Name Time Method Secondary outcomes will examine the spatial relationship between BBB disruption and WMH progression and changes in cognitive scaling. Assessed at each research time point (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
Trial Locations
- Locations (3)
MedStar Washington Hospital Center
🇺🇸Washington, District of Columbia, United States
Suburban Hospital - Johns Hopkins
🇺🇸Bethesda, Maryland, United States
National Institutes of Health Clinical Center
🇺🇸Bethesda, Maryland, United States