Natural History of Stroke: Cause and Development

Evaluation, Pathogenesis, and Treatment of Patients With or at Risk for Cerebrovascular Disease (A Natural History/Disease Pathogenesis Protocol)

The purpose of this study is to learn more about stroke and obtain information that may serve as the basis for future investigations. It will 1) establish a registry of patients with cerebrovascular disease (stroke); 2) characterize the natural history of acute stroke and transient ischemic attacks (TIA)-an interruption of blood flow to the brain that causes stroke symptoms for a short period of time); and 3) evaluate the data to generate ideas for future studies.

Patients 18 years of age or older with suspected acute stroke or TIA may be eligible for this study. Subjects will be recruited from patients who present with stroke at the emergency department of Suburban Hospital in Bethesda, Maryland.

The study will gather data collected from diagnostic and laboratory tests the patient undergoes as part of standard medical care, including findings of medical and neurological examinations and other tests. In addition, studies will be done for research purposes only to gather data about stroke and TIA. These may include the following:

• Blood and urine tests not more than 2 tablespoons of blood will be drawn for various tests.
• Electrocardiogram (EKG) (heart tracing)-electrodes placed on the chest wall detect the heartbeat and heart rhythm.
• Computed tomography (CT) scan of the head-specialized X-rays are used to obtain images of the brain.
• Magnetic resonance imaging (MRI) of the brain-a strong magnetic field and radio waves are used to produce images that provide information about the brain tissue and blood vessels.
• Transcranial Doppler (TCD)-sound waves are used to image the arteries of the brain and neck.
• Echocardiogram-sound waves are used to image the heart and evaluate heart function.

Patients may be asked to return to Suburban Hospital for follow-up testing in 1, 3, and/or 12 months, when some of these tests may be repeated to assess changes over time

Study Overview

• Status: Recruiting
• Conditions: Vascular Diseases; Ischemic Attack, Transient; Cerebrovascular Accident; Brain Disease; Cerebrovascular Disorder

Detailed Description

Study Description:

This is a natural history/disease pathogenesis protocol for evaluation of patients with or at risk of acute stroke, transient ischemic attack (TIA), or other disturbances of cerebrovascular circulation. The purpose of this protocol is to generate natural history data to serve as the basis for future hypothesis-driven protocols as well as to contribute to the clinical and physiological understanding of cerebrovascular disease through the description of disease manifestation and the relationship among clinical, hematologic, and radiologic variables, as well as identifying potential subjects for future studies on stroke and other cerebrovascular diseases.

Objectives:

• To establish a registry of subjects with cerebrovascular disease including clinical, laboratory, and radiological variables associated with hemorrhagic and ischemic stroke, TIA, and other disturbances of cerebrovascular circulation.
• To characterize the natural history of acute stroke, TIA, and other disturbances of cerebrovascular circulation on these variables.
• To evaluate the relationship among these variables by exploratory analyses and to generate hypotheses for future testing.
• To identify potential subjects for research studies on stroke and other cerebrovascular diseases.

Endpoints:

A primary purpose of this observational protocol is to discover and study new imaging biomarkers that are i) relevant to the acute presentation and severity, ii) predictive of clinical outcome, and iii) are useful for stratifying the biological response as reflected in blood-biomarker and gene expression studies. As such, the primary outcome is the results from the imaging studies.

Primary Outcome Measures

Prevalence and type of abnormalities seen on neuroimaging as a function of time from acute insult such as:

• Imaging positive for acute ischemic cerebral vascular syndrome ( AICS positive )[1]
• Presence of a lesion on diffusion, perfusion, and mismatch between the two
• Evidence of a vascular occlusion on MR angiography
• Evidence of a thrombus or hemorrhage on T2* GRE imaging
• Blood-brain barrier disruption as evidence by HARM [2]
• The evolution of these markers with time and treatment

Secondary Outcome Measures

• Stroke severity as measured by NIHSS as a function of time since index event.
• Clinical outcome measured using modified Rankin Scale and Barthel Index
• Gene expression profiles and biomarker levels obtained from blood samples.

• Study Type: Observational
• Enrollment (Estimated): 3000

Contacts and Locations

• Study Contact: Name: Lawrence Latour, Ph.D.; Phone Number: (301) 496-0463; Email: latourl@ninds.nih.gov
• Study Contact Backup: Name: Meghan M Hildreth; Phone Number: (301) 435-2269; Email: meghan.hildreth@nih.gov

Study Locations

• United States
  • District of Columbia
    • Washington, District of Columbia, United States, 20010
      • Recruiting
      • MedStar Washington Hospital Center
      • Contact: Mariam Afzal; Phone Number: 240-281-9832; Email: mariam.afzal@nih.gov
  • Maryland
    • Bethesda, Maryland, United States, 20892
      • Recruiting
      • National Institutes of Health Clinical Center
      • Contact: For more information at the NIH Clinical Center contact Office of Patient Recruitment (OPR); Phone Number: TTY dial 711 800-411-1222; Email: ccopr@nih.gov
    • Bethesda, Maryland, United States, 20814
      • Recruiting
      • Suburban Hospital - Johns Hopkins Medicine
      • Contact: Mariam Afzal; Phone Number: 240-281-9832; Email: mariam.afzal@nih.gov

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No

• Sampling Method: Non-Probability Sample

Study Population

Subjects are recruited from the collaborative stroke programs between NINDS and affiliated hospitals (Suburban Hospital and MedStar Washington Hospital Center) and will be followed for the duration of their hospitalization. Select subjects will then be seen for follow up for up to one year.

Description

• INCLUSION CRITERIA:

In order to be eligible to participate in this study, an individual must meet all of the following criteria:

1. Aged >=18
2. Presented to participating study site (ED, ICU, or inpatient unit) with or at risk of acute stroke, TIA, or other disturbances of cerebrovascular circulation

EXCLUSION CRITERIA:

An individual who meets any of the following criteria will be excluded from participation in this study:

1. Subjects with contraindication to MRI scanning will be excluded from any testing which involves the use of MRI. The contraindications include subjects with the following devices or conditions:

   • Central nervous system aneurysm clips
   • Implanted neural stimulator
   • Implanted cardiac pacemaker or defibrillator
   • Cochlear implant
   • Ocular foreign body (e.g. metal shavings)
   • Insulin pump
   • Metal shrapnel or bullet
   • Any implanted device that is incompatible with MRI

   Subjects with a condition precluding entry in the scanner (e.g. morbid obesity, Claustrophobia, etc.) will not be included in the MRI portion of this study.

2. Pregnancy

Study Plan

How is the study designed?

Design Details

• Observational Models: Cohort
• Time Perspectives: Prospective

Number of groups / cohorts

1

Cohorts and Interventions

Group / Cohort
Patients; Patients with acute stroke symptoms

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Prevalence and type of abnormalities seen on neuroimaging as a function of time from acute insult	Neuroimaging abnormalities, such as:-Imaging positive for acute ischemic cerebral vascular syndrome ( AICS positive )-Presence of a lesion on diffusion, perfusion, and mismatch between the two-Evidence of a vascular occlusion on MR angiography-Evidence of a thrombus or hemorrhage on T2* GRE imaging-Blood-brain barrier disruption as evidence by "HARM"-The evolution of these markers with time and treatment	Post-acute, 24 hours, 5 days/discharge, 30 days

Secondary Outcome Measures

Outcome Measure	Time Frame
Stroke severity as measured by NIHSS as a function of time since index event	Post-acute, 24 hours, 5 days/discharge, 30 days, 3 months, 6 months, 12 months
Clinical outcome measured using modified Rankin Scale and Barthel Index	5 days/discharge, 30 days, 3 months, 6 months, 12 months
Gene expression profiles and biomarker levels obtained from blood samples	Post-acute, 24 hours, 5 days/discharge, 30 days, 3 months, 6 months, 12 months

Collaborators and Investigators

• Sponsor: National Institute of Neurological Disorders and Stroke (NINDS)
• Investigators: Principal Investigator: Lawrence Latour, Ph.D., National Institute of Neurological Disorders and Stroke (NINDS)

Publications and helpful links

General Publications

• Cho YE, Lee H, Bae HR, Kim H, Yun S, Vorn R, Cashion A, Rucker MJ, Afzal M, Latour L, Gill J. Circulating immune cell landscape in patients who had mild ischaemic stroke. Stroke Vasc Neurol. 2022 Aug;7(4):319-327. doi: 10.1136/svn-2021-001224. Epub 2022 Mar 9.
• Luby M, Hsia AW, Nadareishvili Z, Cullison K, Pednekar N, Adil MM, Latour LL. Frequency of Blood-Brain Barrier Disruption Post-Endovascular Therapy and Multiple Thrombectomy Passes in Acute Ischemic Stroke Patients. Stroke. 2019 Aug;50(8):2241-2244. doi: 10.1161/STROKEAHA.119.025914. Epub 2019 Jun 26.
• Hsia AW, Luby M, Cullison K, Burton S, Armonda R, Liu AH, Leigh R, Nadareishvili Z, Benson RT, Lynch JK, Latour LL. Rapid Apparent Diffusion Coefficient Evolution After Early Revascularization. Stroke. 2019 Aug;50(8):2086-2092. doi: 10.1161/STROKEAHA.119.025784. Epub 2019 Jun 26. Erratum In: Stroke. 2019 Sep;50(9):e282.

Helpful Links

• NIH Clinical Center Detailed Web Page

Study record dates

Study Major Dates

• Study Start (Actual): January 26, 2001

Study Registration Dates

• First Submitted: January 24, 2001
• First Submitted That Met QC Criteria: January 24, 2001
• First Posted (Estimated): January 25, 2001

Study Record Updates

• Last Update Posted (Actual): April 17, 2024
• Last Update Submitted That Met QC Criteria: April 16, 2024
• Last Verified: April 4, 2024

More Information

Terms related to this study

• Keywords: Stroke; Natural History; Magnetic Resonance Imaging; TIA; Acute Stroke; MRI (Magnetic Resonance Imaging)
• Additional Relevant MeSH Terms: Cardiovascular Diseases; Central Nervous System Diseases; Nervous System Diseases; Brain Ischemia; Stroke; Vascular Diseases; Ischemic Attack, Transient; Brain Diseases; Cerebrovascular Disorders
• Other Study ID Numbers: 010007; 01-N-0007

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: YES
• IPD Plan Description: .Individual Participant Data that underlie the results reported in the publication, after deidentification.
• IPD Sharing Time Frame: Beginning 3 months and ending 5 years after article publication.
• IPD Sharing Access Criteria: IPD will be shared with researchers who provide a methodologically sound proposal . Proposals should be sent to the corresponding author of the publication.
• IPD Sharing Supporting Information Type: STUDY_PROTOCOL; ICF

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No