Clinical trial NCT00009243: Natural History of Stroke: Cause and Development
Official title: Evaluation, Pathogenesis, and Treatment of Patients With or at Risk for Cerebrovascular Disease (A Natural History/Disease Pathogenesis Protocol)
Study type: OBSERVATIONAL
Overall status: RECRUITING
Conditions: Brain Disease
Ischemic Attack, Transient
Cerebrovascular Accident
Cerebrovascular Disorder
Vascular Diseases
Keywords: Stroke
Natural History
Magnetic Resonance Imaging
MRI (Magnetic Resonance Imaging)
Acute Stroke
TIA
Lead sponsor: National Institutes of Health Clinical Center (CC)
Sponsor class: NIH
First posted: 2001-01-25
Enrollment: 4000
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Observational model: COHORT
Time perspective: PROSPECTIVE
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.

Brief summary: 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

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.

Eligibility criteria: * 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

Primary outcomes:
measure: Prevalence and type of abnormalities seen on neuroimaging as a function of time from acute insult
timeFrame: Post-acute, 24 hours, 5 days/discharge, 30 days
Secondary outcomes:
measure: Stroke severity as measured by NIHSS as a function of time since index event
timeFrame: Post-acute, 24 hours, 5 days/discharge, 30 days, 3 months, 6 months, 12 months
measure: Clinical outcome measured using modified Rankin Scale and Barthel Index
timeFrame: 5 days/discharge, 30 days, 3 months, 6 months, 12 months
measure: Gene expression profiles and biomarker levels obtained from blood samples
timeFrame: Post-acute, 24 hours, 5 days/discharge, 30 days, 3 months, 6 months, 12 months
Other outcomes:
Locations:
city: Washington
country: United States
facility: Medstar Washington Hospital Center
state: District of Columbia
city: Bethesda
country: United States
facility: Suburban Hospital - Johns Hopkins Medicine
state: Maryland
city: Bethesda
country: United States
facility: National Institutes of Health Clinical Center
state: Maryland
Study officials:
affiliation: National Institute of Neurological Disorders and Stroke (NINDS)
name: Lawrence L Latour, Ph.D.
role: PRINCIPAL_INVESTIGATOR
References:
citation: 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.
citation: 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.
citation: 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.