Purpose

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

Eligibility

Eligible Ages
Over 18 Years
Eligible Genders
All
Accepts Healthy Volunteers
No

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.

Study Design

Phase
Study Type
Observational
Observational Model
Cohort
Time Perspective
Prospective

Arm Groups

ArmDescriptionAssigned Intervention
Cohort Stroke patients with white matter hyperintensities (WMH)

Recruiting Locations

Washington Hospital Center
Washington, District of Columbia 20010
Contact:
Richard Benson, M.D.
202-877-3154
bensonric@ninds.nih.gov

More Details

NCT ID
NCT03366129
Status
Recruiting
Sponsor
National Institute of Neurological Disorders and Stroke (NINDS)

Study Contact

Marwah Zagzoug, Ph.D.
(301) 402-6392
marwah.zagzoug@nih.gov

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 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).

Notice

Study information shown on this site is derived from ClinicalTrials.gov (a public registry operated by the National Institutes of Health). The listing of studies provided is not certain to be all studies for which you might be eligible. Furthermore, study eligibility requirements can be difficult to understand and may change over time, so it is wise to speak with your medical care provider and individual research study teams when making decisions related to participation.