Ischemia Care Biomarkers of Acute Stroke Etiology (BASE)

NCT02014896 | Completed DMC

• 1 other identifier: ISCH01
• Study Type: observational
• Target: 1,750
• Locations: 1 country
• Sites: 22

Brief Summary

The proposed study will validate the clinical use of new biomarker blood tests to identify blood components that may differentiate between diverse stroke etiologies and clinical outcomes as listed below:

1. 1.Differentiate between cardioembolic and large artery atherosclerotic ischemic strokes, when hemorrhagic stroke is ruled out.
2. 2.In cases of ischemic strokes of unknown or "cryptogenic" etiology, determine the ability of biomarker blood tests to predict etiology between cardioembolic and large artery atherosclerotic.
3. 3.In cases of cardioembolic ischemic stroke, further differentiation of cardioembolic ischemic strokes into those caused by atrial fibrillation (AF) and those not caused by AF.
4. 4.Differentiate "transient ischemic attacks" (TIAs) from acute ischemic strokes.
5. 5.Differentiate TIAs from non-ischemic "transient neurological events" (TNE) with similar symptoms.

Conditions

Ischemic Stroke; Atrial Fibrillation; Transient Ischemic Attacks; Transient Cerebrovascular Events; Thrombotic Stroke; Stroke of Basilar Artery; Cardioembolic Stroke

Keywords

Ischemic Stroke; Transient Ischemic Attack; Transient Neurological Event; Atrial Fibrillation; Cryptogenic Stroke; Gene Expression; RNA; Anticoagulant; NOAC; Antiplatelet; Cardiac monitoring; Point of Care; tPA; Atheroembolic

Outcome Measures

Primary Outcomes (2)

• Cardioembolic and large vessel stroke stiology

  Determine the ability of ISCDX, a blood test, to differentiate between clinically diagnosed cardioembolic and large artery atherosclerotic ischemic stroke when hemorrhagic stroke is ruled out.

  Up to 60 days.

• TIA differentiation from non ischemic events (TNE).

  Determine the ability of TIADX, a blood test, to identify clinically diagnosed TIAs and differentiate these events from controls, which include TNEs. TNEs represent patients presenting with clinical symptoms similar to a TIA such as migraines, seizures and syncope, which are non-ischemic transient neurological events (TNE).

  Up to 60 days.

Secondary Outcomes (3)

• Cryptogenic stroke

  Up to 60 days.

• Atrial fibrillation and stroke

  Up to 60 days.

• Stroke and TIA, differentiation

  Up to 60 days.

Other Outcomes (1)

• Development of point of care testing for ischemic stroke, transient ischemic attack (TIA), and transient neurological events (TNE).

  Up to 60 days.

Study Arms (4)

Ischemic Stroke

Ischemic stroke subjects presenting within 24 hours from symptom onset will have serial PAX Gene Blood RNA tubes drawn within 18 hours of onset of symptoms upon arrival to the Emergency Department (if available) or hospital; 24 hours +/- 6 hours from symptom onset (if available) and 48 hours+/- 6 hours from symptom onset (if available). Biomarker blood draw

Other: Biomarker blood draw

TIA (Transient Ischemic Attack)

TIA subjects presenting within 24 hours from symptom onset will have serial PAX Gene Blood RNA tubes drawn within 18 hours of onset of symptoms upon arrival to the Emergency Department (if available) or hospital; 24 hours +/- 6 hours from symptom onset (if available) and 48 hours+/- 6 hours from symptom onset (if available). Biomarker blood draw

Other: Biomarker blood draw

Non-Ischemic TNE

Non-Ischemic Transient Neurological Event (TNE) subjects will have serial PAX Gene Blood RNA tubes drawn within 18 hours of onset of symptoms upon arrival to the Emergency Department or hospital. Biomarker blood draw

Other: Biomarker blood draw

Control

Control group subjects will have PAX Gene Blood RNA tubes drawn within 8 hours of arrival to the Emergency Department or hospital. Control group matched with ischemic stroke and TIA subjects for age, race, gender, smoking history with at least one of the following vascular risk factors: diabetes, hypertension, atrial fibrillation, hyperlipidemia. Biomarker blood draw

Other: Biomarker blood draw

Interventions

Biomarker blood draw OTHER

Comparison of gene expression profiles using RNA isolated from whole blood.

Also known as: PAX Gene Blood RNA tube, PreAnalytiX, Germnay

Control; Ischemic Stroke; Non-Ischemic TNE; TIA (Transient Ischemic Attack)

Eligibility Criteria

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

Study Population

Subjects eligible for enrollment include: 1. Ischemic stroke within 24 hours of symptom onset. 2. Transient Ischemic Attack (TIA) within 24 hours of symptom onset. 3. Non-ischemic transient neurologic event (TNE) within 24 hours of onset. 4. Normal controls that will be non-neurologic patients who are matched with the other ischemic stroke and TIA patients for age, race, gender and smoking plus one or more of the following vascular risk factors: diabetes, hypertension, atrial fibrillation, hyperlipidemia.

You may qualify if:

• Patients \>18 years of age
• Signs and symptoms suggestive of AIS or TIA
• One of the following:
• BASE - Arrival to the emergency department or hospital within 18 hrs of symptom onset or last known normal time
• BASE 24 - Arrival to the emergency department or hospital within 24 hours +/- 6 hours (i.e. 18 - 30 hour window) of symptom onset or last known normal time and clinical evidence suggesting Acute Ischemic Stroke.
• Head CT or MRI ruling out other pathology such as vascular malformation, hemorrhage, tumor or abscess which would likely be responsible for presenting neurologic symptoms
• Informed consent obtained

You may not qualify if:

• Any central nervous system infection, i.e. meningitis or encephalitis in the past 30 days
• Any form of head trauma, stroke or intracranial hemorrhage in the past 30 days
• Known primary or metastatic cancer involving the brain
• Active Cancer defined as a diagnosis of cancer, within 6 months before enrollment, any treatment for cancer within the previous 6 months, or recurrent or metastatic cancer.
• Autoimmune diseases: such as lupus, rheumatoid arthritis, Crohn's disease, ulcerative colitis
• Active infectious diseases (eg. HIV/AIDS, hepatitis C)
• Any underlying medical condition which in the opinion of the investigator would prohibit the patient from providing informed consent
• Major surgery within three months prior to the index event

Sponsors & Collaborators

• Ischemia Care LLC: lead

Study Sites (22)

Dignity Health Mercury San Juan

Sacramento, California, 95816, United States

Location

Zuckerberg San Francisco General Hospital (UCSF)

San Francisco, California, 94110, United States

Location

University of California San Francisco Medical Center Hospital

San Francisco, California, 94143, United States

Location

Henry Ford Hospital

Detroit, Michigan, 48202, United States

Location

William Beaumont Hospital - Beaumont Health System

Royal Oak, Michigan, 48073, United States

Location

Washington University, University Hospital in St Louis

St Louis, Missouri, 63110, United States

Location

The Stroke Center at Saint Barnabas Medical Center

Livingston, New Jersey, 07039, United States

Location

Montefiore Medical Center (University Hospital for Albert Einstein College of Medicine)

The Bronx, New York, 10467, United States

Location

University of North Carolina Department of Neurology - Stroke Division

Chapel Hill, North Carolina, 27599, United States

Location

Duke University Medical Center

Durham, North Carolina, 27710, United States

Location

Wake Forest School of Medicine

Winston-Salem, North Carolina, 27157, United States

Location

Cleveland Clinic

Cleveland, Ohio, 44195, United States

Location

Riverside Methodist Hospital/ Ohio Health Research Institute

Columbus, Ohio, 43214, United States

Location

Kettering Medical Center

Kettering, Ohio, 45429, United States

Location

Genesis Healthcare System

Zanesville, Ohio, 43701, United States

Location

Providence Health and Services

Portland, Oregon, 97225, United States

Location

University of Pennsylvania Medical Center

Philadelphia, Pennsylvania, 19104, United States

Location

Allegheny General Hospital

Pittsburgh, Pennsylvania, 15212, United States

Location

Medical University of South Carolina

Charleston, South Carolina, 29425, United States

Location

Chattanooga Center for Neurologic Research

Chattanooga, Tennessee, 37403, United States

Location

Baylor College of Medicine

Houston, Texas, 77030, United States

Location

UT Health Department of Neurology

Houston, Texas, 77030, United States

Location

Related Publications (18)

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• Stead LG, Gilmore RM, Bellolio MF, Jain A, Rabinstein AA, Decker WW, Agarwal D, Brown RD Jr. Cardioembolic but not other stroke subtypes predict mortality independent of stroke severity at presentation. Stroke Res Treat. 2011;2011:281496. doi: 10.4061/2011/281496. Epub 2011 Oct 10.

  PMID: 22007347 BACKGROUND

• Kamel et al. J Stroke Cerebrolvasc Dis; 2009 Nov-Dec;18(6):453-7. The risk of stroke recurrence is four times greater among prior stroke patients with newly detected AF.

  BACKGROUND

• Wolf PA, Abbott RD, Kannel WB. Atrial fibrillation as an independent risk factor for stroke: the Framingham Study. Stroke. 1991 Aug;22(8):983-8. doi: 10.1161/01.str.22.8.983.

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• Hart RG, Pearce LA, Aguilar MI. Meta-analysis: antithrombotic therapy to prevent stroke in patients who have nonvalvular atrial fibrillation. Ann Intern Med. 2007 Jun 19;146(12):857-67. doi: 10.7326/0003-4819-146-12-200706190-00007.

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• Furie KL, Kasner SE, Adams RJ, Albers GW, Bush RL, Fagan SC, Halperin JL, Johnston SC, Katzan I, Kernan WN, Mitchell PH, Ovbiagele B, Palesch YY, Sacco RL, Schwamm LH, Wassertheil-Smoller S, Turan TN, Wentworth D; American Heart Association Stroke Council, Council on Cardiovascular Nursing, Council on Clinical Cardiology, and Interdisciplinary Council on Quality of Care and Outcomes Research. Guidelines for the prevention of stroke in patients with stroke or transient ischemic attack: a guideline for healthcare professionals from the american heart association/american stroke association. Stroke. 2011 Jan;42(1):227-76. doi: 10.1161/STR.0b013e3181f7d043. Epub 2010 Oct 21.

  PMID: 20966421 BACKGROUND

• Jickling GC, Xu H, Stamova B, Ander BP, Zhan X, Tian Y, Liu D, Turner RJ, Mesias M, Verro P, Khoury J, Jauch EC, Pancioli A, Broderick JP, Sharp FR. Signatures of cardioembolic and large-vessel ischemic stroke. Ann Neurol. 2010 Nov;68(5):681-92. doi: 10.1002/ana.22187.

  PMID: 21031583 BACKGROUND

• Jickling GC, Zhan X, Stamova B, Ander BP, Tian Y, Liu D, Sison SM, Verro P, Johnston SC, Sharp FR. Ischemic transient neurological events identified by immune response to cerebral ischemia. Stroke. 2012 Apr;43(4):1006-12. doi: 10.1161/STROKEAHA.111.638577. Epub 2012 Feb 2.

  PMID: 22308247 BACKGROUND

• Tang Y, Lu A, Aronow BJ, Sharp FR. Blood genomic responses differ after stroke, seizures, hypoglycemia, and hypoxia: blood genomic fingerprints of disease. Ann Neurol. 2001 Dec;50(6):699-707. doi: 10.1002/ana.10042.

  PMID: 11761467 BACKGROUND

• Tang Y, Xu H, Du X, Lit L, Walker W, Lu A, Ran R, Gregg JP, Reilly M, Pancioli A, Khoury JC, Sauerbeck LR, Carrozzella JA, Spilker J, Clark J, Wagner KR, Jauch EC, Chang DJ, Verro P, Broderick JP, Sharp FR. Gene expression in blood changes rapidly in neutrophils and monocytes after ischemic stroke in humans: a microarray study. J Cereb Blood Flow Metab. 2006 Aug;26(8):1089-102. doi: 10.1038/sj.jcbfm.9600264. Epub 2006 Jan 4.

  PMID: 16395289 BACKGROUND

• Xu H, Tang Y, Liu DZ, Ran R, Ander BP, Apperson M, Liu XS, Khoury JC, Gregg JP, Pancioli A, Jauch EC, Wagner KR, Verro P, Broderick JP, Sharp FR. Gene expression in peripheral blood differs after cardioembolic compared with large-vessel atherosclerotic stroke: biomarkers for the etiology of ischemic stroke. J Cereb Blood Flow Metab. 2008 Jul;28(7):1320-8. doi: 10.1038/jcbfm.2008.22. Epub 2008 Apr 2.

  PMID: 18382470 BACKGROUND

• Stamova B, Xu H, Jickling G, Bushnell C, Tian Y, Ander BP, Zhan X, Liu D, Turner R, Adamczyk P, Khoury JC, Pancioli A, Jauch E, Broderick JP, Sharp FR. Gene expression profiling of blood for the prediction of ischemic stroke. Stroke. 2010 Oct;41(10):2171-7. doi: 10.1161/STROKEAHA.110.588335. Epub 2010 Aug 26.

  PMID: 20798371 BACKGROUND

• Jickling GC, Stamova B, Ander BP, Zhan X, Tian Y, Liu D, Xu H, Johnston SC, Verro P, Sharp FR. Profiles of lacunar and nonlacunar stroke. Ann Neurol. 2011 Sep;70(3):477-85. doi: 10.1002/ana.22497. Epub 2011 Jul 27.

  PMID: 21796664 BACKGROUND

• Zhan X, Jickling GC, Tian Y, Stamova B, Xu H, Ander BP, Turner RJ, Mesias M, Verro P, Bushnell C, Johnston SC, Sharp FR. Transient ischemic attacks characterized by RNA profiles in blood. Neurology. 2011 Nov 8;77(19):1718-24. doi: 10.1212/WNL.0b013e318236eee6. Epub 2011 Oct 12.

  PMID: 21998319 BACKGROUND

• Jickling GC, Stamova B, Ander BP, Zhan X, Liu D, Sison SM, Verro P, Sharp FR. Prediction of cardioembolic, arterial, and lacunar causes of cryptogenic stroke by gene expression and infarct location. Stroke. 2012 Aug;43(8):2036-41. doi: 10.1161/STROKEAHA.111.648725. Epub 2012 May 24.

  PMID: 22627989 BACKGROUND

• Jauch EC, Barreto AD, Broderick JP, Char DM, Cucchiara BL, Devlin TG, Haddock AJ, Hicks WJ, Hiestand BC, Jickling GC, June J, Liebeskind DS, Lowenkopf TJ, Miller JB, O'Neill J, Schoonover TL, Sharp FR, Peacock WF. Biomarkers of Acute Stroke Etiology (BASE) Study Methodology. Transl Stroke Res. 2017 May 5;8(5):424-8. doi: 10.1007/s12975-017-0537-3. Online ahead of print.

  PMID: 28477280 BACKGROUND

Biospecimen

Retention: SAMPLES WITHOUT DNA

Biospecimen will be whole blood samples.

MeSH Terms

Conditions

Ischemic Stroke; Atrial Fibrillation; Ischemic Attack, Transient; Thrombotic Stroke; Embolic Stroke

Condition Hierarchy (Ancestors)

Stroke; Cerebrovascular Disorders; Brain Diseases; Central Nervous System Diseases; Nervous System Diseases; Vascular Diseases; Cardiovascular Diseases; Arrhythmias, Cardiac; Heart Diseases; Pathologic Processes; Pathological Conditions, Signs and Symptoms; Brain Ischemia

Study Officials

• Frank Peacock, MD

  Ischemia Care

  PRINCIPAL INVESTIGATOR

• Edward Jauch, MD

  Medical University of South Carolina

  PRINCIPAL INVESTIGATOR

Study Design

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

Study Record Dates

• First Submitted: December 5, 2013
• First Posted: December 18, 2013
• Study Start: December 1, 2013
• Primary Completion: November 1, 2019
• Study Completion: January 1, 2020
• Last Updated: July 8, 2020

Record last verified: 2020-07

Data Sharing

• IPD Sharing: Will not share

Locations

US (22)