Blood-Brain Barrier Disruption in People With White Matter Hyperintensities Who Have Had a Stroke



Status:Recruiting
Conditions:Healthy Studies, Neurology
Therapuetic Areas:Neurology, Other
Healthy:No
Age Range:18 - Any
Updated:3/27/2019
Start Date:September 6, 2018
End Date:January 1, 2034
Contact:Marwah Zagzoug, Ph.D.
Email:marwah.zagzoug@nih.gov
Phone:(301) 402-6392

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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.

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.

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).

- INCLUSION CRITERIA:

- Age greater than or equal to 18

- Have been admitted to one of the study sites for evaluation of stroke-like symptoms (
qualifying event ) such as difficulty moving or speaking, blurred vision, dizziness or
balance issues; and had an MRI scan. Symptoms must be attributable to a stroke or TIA
with no other definitive cause identified at the time of screening.

- Provides written informed consent prior to study participation OR is able to provided
assent and consent is provided by a qualifying LAR.

- Is willing to return to one of the two study sites to initiate serial study visits
between 3-4 months whenever possible, but could be up to 6 months from the qualifying
event and continue participation for at least one year.

Is willing to appoint a Durable Power of Attorney (DPA) for NIH research

EXCLUSION CRITERIA:

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.

- 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 MoCA score less than or equal to 13 during screening assessment.
We found this trial at
3
sites
110 Irving St NW
Washington, District of Columbia 20010
(202) 877-7000
Phone: 202-877-3154
Washington Hosp Ctr MedStar Washington Hospital Center is a not-for-profit, 926-bed, major teaching and research...
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8600 Old Georgetown Road
Bethesda, Maryland 20814
301-896-3100
Phone: 301-496-6231
Suburban Hospital Suburban Hospital is a community-based, not-for-profit hospital serving Montgomery County and the surrounding...
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9000 Rockville Pike
Bethesda, Maryland 20892
301-496-2563
Phone: 800-411-1222
National Institutes of Health Clinical Center The National Institutes of Health (NIH) Clinical Center in...
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