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

NCT03366129 | Completed

• 2 other identifiers: 18002018-N-0020
• Study Type: observational
• Target: 81
• Locations: 1 country
• Sites: 3

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.

Conditions

Cerebrovascular Disorder; Stroke; Aging

Keywords

CEREBROVASCULAR DISEASE; Vascular Cognitive Impairment; Stroke; Permeability Imaging; Natural History

Outcome Measures

Primary Outcomes (1)

• 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).

  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.

  Assessed at each research time point

Study Arms (1)

Cohort

Stroke patients with white matter hyperintensities (WMH)

Eligibility Criteria

• Age: 18 Years - 99 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)
• Sampling Method: Non-Probability Sample

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.

You may qualify if:

• 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.

You may not qualify if:

• 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 six-item screener score less than 4, during screening.

Sponsors & Collaborators

• National Institute of Neurological Disorders and Stroke (NINDS): lead

Study Sites (3)

MedStar Washington Hospital Center

Washington D.C., District of Columbia, 20010, United States

Location

Suburban Hospital - Johns Hopkins

Bethesda, Maryland, 20814, United States

Location

National Institutes of Health Clinical Center

Bethesda, Maryland, 20892, United States

Location

Related Publications (1)

• 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.

  PMID: 23285132 BACKGROUND

Related Links

• NIH Clinical Center Detailed Web Page

MeSH Terms

Conditions

Cerebrovascular Disorders; Stroke

Condition Hierarchy (Ancestors)

Brain Diseases; Central Nervous System Diseases; Nervous System Diseases; Vascular Diseases; Cardiovascular Diseases

Study Officials

• Clinton B Wright, M.D.

  National Institute of Neurological Disorders and Stroke (NINDS)

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: observational
• Observational Model: COHORT
• Time Perspective: PROSPECTIVE
• Sponsor Type: NIH
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: December 7, 2017
• First Posted: December 8, 2017
• Study Start: September 6, 2018
• Primary Completion: December 18, 2023
• Study Completion: December 18, 2023
• Last Updated: April 29, 2026

Record last verified: 2025-06-27

Locations

US (3)