Blood-Brain Barrier Disruption in People With White Matter Hyperintensities Who Have Had a Stroke
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|ClinicalTrials.gov Identifier: NCT03366129|
Recruitment Status : Recruiting
First Posted : December 8, 2017
Last Update Posted : July 16, 2019
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.
To better understand the how blood-brain barrier disruption is related to white matter hyperintensities.
Adults at least 18 years old who have been admitted to a study site with stroke-like symptoms
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.
|Condition or disease|
|Cerebrovascular Disorder Stroke Aging|
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 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.
Design: Patients admitted to one of the two enrolling sites (Suburban Hospital and Medstar Washington Hospital Center) who had a stroke evaluation by the NIH stroke team will be eligible for enrollment. Enrolled subjects who meet the inclusion/exclusion criteria will be followed serially with MRI. The first research evaluation will be within 3-4 months of the qualifying event whenever possible, but could be up to 6 months. 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.
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 Type :||Observational|
|Estimated Enrollment :||310 participants|
|Official Title:||The Natural History of Blood-Brain Barrier Disruption in Stroke Patients With White Matter Hyperintensities (A Cohort Study)|
|Actual Study Start Date :||September 6, 2018|
|Estimated Primary Completion Date :||January 1, 2027|
|Estimated Study Completion Date :||January 1, 2034|
a cohort of stroke patients with white matter hyperintensities (WMH)
- Outcome will be based on the relationship between the presence of BBB disruption in the NAWM and the progression of WMH over time. BBB disruption will be measured with dynamic susceptibility contrast (DSC) MRI and WMH will be measured with FLAI... [ Time Frame: Ongoing ]
- Exploratory imaging of a variety of MRI sequences, changes in brain volume, changes in other markers of cerebrovascular disease, and clinical changes over time. [ Time Frame: Ongoing ]
To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.
Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT03366129
|Contact: Marwah Zagzoug, Ph.D.||(301) email@example.com|
|United States, District of Columbia|
|Washington Hospital Center||Recruiting|
|Washington, District of Columbia, United States, 20010|
|Contact: Richard Benson, M.D. 202-877-3154 firstname.lastname@example.org|
|United States, Maryland|
|Bethesda, Maryland, United States, 20814|
|Contact: Zurab Nadareishvili, M.D. 301-496-6231 email@example.com|
|National Institutes of Health Clinical Center||Recruiting|
|Bethesda, Maryland, United States, 20892|
|Contact: For more information at the NIH Clinical Center contact Office of Patient Recruitment (OPR) 800-411-1222 ext TTY8664111010 firstname.lastname@example.org|
|Principal Investigator:||Clinton Wright, M.D.||National Institute of Neurological Disorders and Stroke (NINDS)|