Working...
ClinicalTrials.gov
ClinicalTrials.gov Menu

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

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Know the risks and potential benefits of clinical studies and talk to your health care provider before participating. Read our disclaimer for details.
ClinicalTrials.gov Identifier: NCT03366129
Recruitment Status : Recruiting
First Posted : December 8, 2017
Last Update Posted : July 16, 2019
Sponsor:
Information provided by (Responsible Party):
National Institutes of Health Clinical Center (CC) ( National Institute of Neurological Disorders and Stroke (NINDS) )

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.


Condition or disease
Cerebrovascular Disorder Stroke Aging

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).


Layout table for study information
Study Type : Observational
Estimated Enrollment : 310 participants
Observational Model: Cohort
Time Perspective: Prospective
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

Group/Cohort
1
a cohort of stroke patients with white matter hyperintensities (WMH)



Primary Outcome Measures :
  1. 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 ]

Secondary Outcome Measures :
  1. 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 ]


Information from the National Library of Medicine

Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the contacts provided below. For general information, Learn About Clinical Studies.


Layout table for eligibility information
Ages Eligible for Study:   18 Years and older   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
Sampling Method:   Non-Probability Sample
Study Population
stroke patients with white matter hyperintensities (WMH)
Criteria
  • 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.

Information from the National Library of Medicine

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


Contacts
Layout table for location contacts
Contact: Marwah Zagzoug, Ph.D. (301) 402-6392 marwah.zagzoug@nih.gov

Locations
Layout table for location information
United States, District of Columbia
Washington Hospital Center Recruiting
Washington, District of Columbia, United States, 20010
Contact: Richard Benson, M.D.    202-877-3154    bensonric@ninds.nih.gov   
United States, Maryland
Suburban Hospital Recruiting
Bethesda, Maryland, United States, 20814
Contact: Zurab Nadareishvili, M.D.    301-496-6231    nadareishviliz@ninds.nih.gov   
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    prpl@cc.nih.gov   
Sponsors and Collaborators
National Institute of Neurological Disorders and Stroke (NINDS)
Investigators
Layout table for investigator information
Principal Investigator: Clinton Wright, M.D. National Institute of Neurological Disorders and Stroke (NINDS)

Additional Information:
Publications:
Layout table for additonal information
Responsible Party: National Institute of Neurological Disorders and Stroke (NINDS)
ClinicalTrials.gov Identifier: NCT03366129     History of Changes
Other Study ID Numbers: 180020
18-N-0020
First Posted: December 8, 2017    Key Record Dates
Last Update Posted: July 16, 2019
Last Verified: June 24, 2019

Keywords provided by National Institutes of Health Clinical Center (CC) ( National Institute of Neurological Disorders and Stroke (NINDS) ):
CEREBROVASCULAR DISEASE
Vascular Cognitive Impairment
Stroke
Permeability Imaging

Additional relevant MeSH terms:
Layout table for MeSH terms
Stroke
Cerebrovascular Disorders
Brain Diseases
Central Nervous System Diseases
Nervous System Diseases
Vascular Diseases
Cardiovascular Diseases