Translational Immunodiagnostics in Stroke (TrImS)

NCT05300997 | Recruiting

• 1 other identifier: TrImS-RAINER-2021
• Study Type: observational
• Target: 650
• Locations: 1 country
• Sites: 1

Brief Summary

In adult patients presenting to emergency departments within 24 hours of symptom onset with suspected acute stroke, we aim:

1. 1.to identify early brain- and pathology-specific circulating, whole blood, plasma and serum panorOmic biomarkers that enable early acute stroke detection, diagnosis, dynamics, differentiation, monitoring, prediction and prognosis.
2. 2.to identify early brain- and pathology-specific, panorOmic biomarkers in saliva that enable early acute stroke detection, diagnosis, dynamics, differentiation, monitoring, prediction and prognosis.
3. 3.to derive biomarker platforms of models for early acute stroke detection, diagnosis, dynamics, differentiation, monitoring, prediction and prognosis
4. 4.to validate these models in independent and external datasets

Conditions

Acute Ischemic Stroke; Haemorrhagic Stroke; Transient Ischemic Attacks; Cardioembolic Stroke; Large-Artery Atherosclerosis (Embolus/Thrombosis); Small Vessel Disease; Stroke of Other Determined Etiology; Stroke of Undetermined Etiology; Atrial Fibrillation; Stroke of Anterior Cerebral Artery; Stroke of Middle Cerebral Artery; Stroke of Basilar Artery

Keywords

acute stroke; emergency medicine; diagnostics; molecular; genomics and transcriptomics; proteomics

Outcome Measures

Primary Outcomes (1)

• Differentiation of stroke from non-stroke in patients with suspected stroke

  Stroke is defined as either a) the presence of intracerebral haemorrhage with imaging; or b) intracerebral ischaemia with imaging; or c) clinical features of stroke in the absence of positive imaging persisting after 24 hours (cryptogenic stroke). Cryptogenic stroke is defined according to TOAST as stroke not caused by large artery atherosclerosis, cardioembolism, small vessel occlusion and stroke of other aetiology. Non-stroke includes TIA and stroke mimics. TIA is defined as the resolution of stroke-like symptoms within 24 hours of onset and the absence of acute cerebral abnormalities on CT/MRI. Stroke mimics are defined as diseases caused by neurologic symptoms that resemble a stroke. For example, seizure, complex migraines, demyelinating disease, meningitis, glucose level variations and metabolic disorders (hypoglycemia), tumors, non-cerebrovascular diseases such as epilepsy, and dementia.

  Up to 24 hours

Secondary Outcomes (9)

• Differentiation of Transient Ischaemic Attack (TIA) from Transient non-neurological events (TNE) in patients with suspected acute stroke

  Up to 24 hours

• Differentiation of acute ischaemic stroke(AIS) from haemorrhagic stroke(HS) in patients with suspected acute stroke before and after imaging

  Up to 24 hours

• Differentiation of AIS-LVAD from AIS-SVD from AIS-CE in patients with suspected acute stroke

  Up to 24 hours

• Differentiation of stroke of known origin (AIS/HS) from cryptogenic stroke in patients with suspected acute stroke

  Up to 24 hours

• Differentiation of early stroke onset (<4.5 hours) from late stroke onset (>4.5 hours)

  Up to 24 hours

Study Arms (6)

Haemorrhagic Stroke [N=100]

Haemorrhagic stroke subjects presenting within 24 hours from symptom onset will have serial whole blood and saliva drawn a) in the emergency department (if available) or hospital within 24 hours of the onset of symptoms; b) 18 hours +/- 6 hours from symptom onset (if available); and c) 30 hours+/- 6 hours from symptom onset (if available).

Diagnostic Test: Biomarker blood draw and saliva collection

Acute Ischaemic Stroke [N=300]

Acute Ischaemic stroke subjects presenting within 24 hours from symptom onset will have serial whole blood and saliva drawn a) in the emergency department (if available) or hospital within 24 hours of the onset of symptoms; b) 18 hours +/- 6 hours from symptom onset (if available); and c) 30 hours+/- 6 hours from symptom onset (if available).

Diagnostic Test: Biomarker blood draw and saliva collection

Stroke of uncertain origin [N=45]

Stroke of uncertain origin subjects presenting within 24 hours from symptom onset will have serial whole blood and saliva drawn a) in the emergency department (if available) or hospital within 24 hours of the onset of symptoms; b) 18 hours +/- 6 hours from symptom onset (if available); and c) 30 hours+/- 6 hours from symptom onset (if available).

Diagnostic Test: Biomarker blood draw and saliva collection

Transient Ischemic Attack (TIA) [N=75]

TIA subjects presenting within 24 hours from symptom onset will have serial whole blood and saliva drawn a) in the emergency department (if available) or hospital within 24 hours of the onset of symptoms; b) 18 hours +/- 6 hours from symptom onset (if available); and c) 30 hours+/- 6 hours from symptom onset (if available).

Diagnostic Test: Biomarker blood draw and saliva collection

Stroke Mimics [N=30]

Stroke Mimics subjects presenting within 24 hours from symptom onset will have serial whole blood and saliva drawn a) in the emergency department (if available) or hospital within 24 hours of the onset of symptoms; b) 18 hours +/- 6 hours from symptom onset (if available); and c) 30 hours+/- 6 hours from symptom onset (if available).

Diagnostic Test: Biomarker blood draw and saliva collection

Control Subjects [N=100]

Control group subjects, if they agree, will have serial whole blood and saliva drawn a) in the emergency department (if available) or hospital on day 1; b) 18 hours +/- 6 hours after sample 1 (if available); and c) 30 hours+/- 6 hours after sample 1 (if available).

Diagnostic Test: Biomarker blood draw and saliva collection

Interventions

Biomarker blood draw and saliva collection DIAGNOSTIC_TEST

Three peripheral 10mL blood sample (if available) Three 1 - 3mL salivary samples (if available)

Acute Ischaemic Stroke [N=300]; Control Subjects [N=100]; Haemorrhagic Stroke [N=100]; Stroke Mimics [N=30]; Stroke of uncertain origin [N=45]; Transient Ischemic Attack (TIA) [N=75]

Eligibility Criteria

• Age: 18 Years - 100 Years
• Sex: all
• Healthy Volunteers: Yes
• Age Groups: Adult (18-64), Older Adult (65+)
• Sampling Method: Non-Probability Sample

Study Population

Suspected stroke patients presenting to emergency department within 24 hours of symptom onset.

You may qualify if:

• Patients eligible for enrolment include:
• Adults ≥18 years of age.
• Suspected acute stroke. Defined as either FAST-positive, or LAPSS-positive or ROSIER\>0
• Within 24 hours of symptom onset.
• Informed consent.
• Control subjects will be drawn from two groups:
• Non-neurologic patients who are matched with TIA and stroke cases (AIS, HS) for age, race, gender and smoking plus one or more of the following vascular risk factors: diabetes, hypertension, atrial fibrillation, hyperlipidaemia.
• Relatives or accompanying friends.
• Note that we will include and collect samples from the following cases if they present as suspected stroke and are recruited \<24 hours from symptom onset.
• Any central nervous system infection, i.e. meningitis or encephalitis in the past 30 days
• Any form of head trauma, stroke or intracranial haemorrhage in the past 30 days
• Known primary or metastatic cancer involving the brain
• Active cancer is 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 (e.g. HIV/AIDS, hepatitis C)

You may not qualify if:

• Clear onset of acute symptoms \>24 hours.

Sponsors & Collaborators

• The University of Hong Kong: lead

Study Sites (1)

Hong Kong University

Hong Kong, China

RECRUITING

Related Publications (17)

• Lozano R, Naghavi M, Foreman K, Lim S, Shibuya K, Aboyans V, Abraham J, Adair T, Aggarwal R, Ahn SY, Alvarado M, Anderson HR, Anderson LM, Andrews KG, Atkinson C, Baddour LM, Barker-Collo S, Bartels DH, Bell ML, Benjamin EJ, Bennett D, Bhalla K, Bikbov B, Bin Abdulhak A, Birbeck G, Blyth F, Bolliger I, Boufous S, Bucello C, Burch M, Burney P, Carapetis J, Chen H, Chou D, Chugh SS, Coffeng LE, Colan SD, Colquhoun S, Colson KE, Condon J, Connor MD, Cooper LT, Corriere M, Cortinovis M, de Vaccaro KC, Couser W, Cowie BC, Criqui MH, Cross M, Dabhadkar KC, Dahodwala N, De Leo D, Degenhardt L, Delossantos A, Denenberg J, Des Jarlais DC, Dharmaratne SD, Dorsey ER, Driscoll T, Duber H, Ebel B, Erwin PJ, Espindola P, Ezzati M, Feigin V, Flaxman AD, Forouzanfar MH, Fowkes FG, Franklin R, Fransen M, Freeman MK, Gabriel SE, Gakidou E, Gaspari F, Gillum RF, Gonzalez-Medina D, Halasa YA, Haring D, Harrison JE, Havmoeller R, Hay RJ, Hoen B, Hotez PJ, Hoy D, Jacobsen KH, James SL, Jasrasaria R, Jayaraman S, Johns N, Karthikeyan G, Kassebaum N, Keren A, Khoo JP, Knowlton LM, Kobusingye O, Koranteng A, Krishnamurthi R, Lipnick M, Lipshultz SE, Ohno SL, Mabweijano J, MacIntyre MF, Mallinger L, March L, Marks GB, Marks R, Matsumori A, Matzopoulos R, Mayosi BM, McAnulty JH, McDermott MM, McGrath J, Mensah GA, Merriman TR, Michaud C, Miller M, Miller TR, Mock C, Mocumbi AO, Mokdad AA, Moran A, Mulholland K, Nair MN, Naldi L, Narayan KM, Nasseri K, Norman P, O'Donnell M, Omer SB, Ortblad K, Osborne R, Ozgediz D, Pahari B, Pandian JD, Rivero AP, Padilla RP, Perez-Ruiz F, Perico N, Phillips D, Pierce K, Pope CA 3rd, Porrini E, Pourmalek F, Raju M, Ranganathan D, Rehm JT, Rein DB, Remuzzi G, Rivara FP, Roberts T, De Leon FR, Rosenfeld LC, Rushton L, Sacco RL, Salomon JA, Sampson U, Sanman E, Schwebel DC, Segui-Gomez M, Shepard DS, Singh D, Singleton J, Sliwa K, Smith E, Steer A, Taylor JA, Thomas B, Tleyjeh IM, Towbin JA, Truelsen T, Undurraga EA, Venketasubramanian N, Vijayakumar L, Vos T, Wagner GR, Wang M, Wang W, Watt K, Weinstock MA, Weintraub R, Wilkinson JD, Woolf AD, Wulf S, Yeh PH, Yip P, Zabetian A, Zheng ZJ, Lopez AD, Murray CJ, AlMazroa MA, Memish ZA. Global and regional mortality from 235 causes of death for 20 age groups in 1990 and 2010: a systematic analysis for the Global Burden of Disease Study 2010. Lancet. 2012 Dec 15;380(9859):2095-128. doi: 10.1016/S0140-6736(12)61728-0.

  PMID: 23245604 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

• Stamova B, Jickling GC, Ander BP, Zhan X, Liu D, Turner R, Ho C, Khoury JC, Bushnell C, Pancioli A, Jauch EC, Broderick JP, Sharp FR. Gene expression in peripheral immune cells following cardioembolic stroke is sexually dimorphic. PLoS One. 2014 Jul 18;9(7):e102550. doi: 10.1371/journal.pone.0102550. eCollection 2014.

  PMID: 25036109 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

• Tian Y, Stamova B, Jickling GC, Liu D, Ander BP, Bushnell C, Zhan X, Davis RR, Verro P, Pevec WC, Hedayati N, Dawson DL, Khoury J, Jauch EC, Pancioli A, Broderick JP, Sharp FR. Effects of gender on gene expression in the blood of ischemic stroke patients. J Cereb Blood Flow Metab. 2012 May;32(5):780-91. doi: 10.1038/jcbfm.2011.179. Epub 2011 Dec 14.

  PMID: 22167233 BACKGROUND

• Lo YM, Rainer TH, Chan LY, Hjelm NM, Cocks RA. Plasma DNA as a prognostic marker in trauma patients. Clin Chem. 2000 Mar;46(3):319-23.

  PMID: 10702517 BACKGROUND

• Loo JA, Yan W, Ramachandran P, Wong DT. Comparative human salivary and plasma proteomes. J Dent Res. 2010 Oct;89(10):1016-23. doi: 10.1177/0022034510380414. Epub 2010 Aug 25.

  PMID: 20739693 BACKGROUND

• Dagonnier M, Donnan GA, Davis SM, Dewey HM, Howells DW. Acute Stroke Biomarkers: Are We There Yet? Front Neurol. 2021 Feb 5;12:619721. doi: 10.3389/fneur.2021.619721. eCollection 2021.

  PMID: 33633673 BACKGROUND

• Rainer TH, Wong LK, Lam W, Yuen E, Lam NY, Metreweli C, Lo YM. Prognostic use of circulating plasma nucleic acid concentrations in patients with acute stroke. Clin Chem. 2003 Apr;49(4):562-9. doi: 10.1373/49.4.562.

  PMID: 12651807 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

• Puig N, Jimenez-Xarrie E, Camps-Renom P, Benitez S. Search for Reliable Circulating Biomarkers to Predict Carotid Plaque Vulnerability. Int J Mol Sci. 2020 Nov 3;21(21):8236. doi: 10.3390/ijms21218236.

  PMID: 33153204 BACKGROUND

• Glushakova OY, Glushakov AV, Miller ER, Valadka AB, Hayes RL. Biomarkers for acute diagnosis and management of stroke in neurointensive care units. Brain Circ. 2016 Jan-Mar;2(1):28-47. doi: 10.4103/2394-8108.178546. Epub 2016 Mar 11.

  PMID: 30276272 BACKGROUND

• Lam NY, Rainer TH, Chan LY, Joynt GM, Lo YM. Time course of early and late changes in plasma DNA in trauma patients. Clin Chem. 2003 Aug;49(8):1286-91. doi: 10.1373/49.8.1286.

  PMID: 12881444 BACKGROUND

• Lam NY, Rainer TH, Wong LK, Lam W, Lo YM. Plasma DNA as a prognostic marker for stroke patients with negative neuroimaging within the first 24 h of symptom onset. Resuscitation. 2006 Jan;68(1):71-8. doi: 10.1016/j.resuscitation.2005.05.021. Epub 2005 Dec 1.

  PMID: 16325316 BACKGROUND

• Graham CA, Chan RW, Chan DY, Chan CP, Wong LK, Rainer TH. Matrix metalloproteinase 9 mRNA: an early prognostic marker for patients with acute stroke. Clin Biochem. 2012 Mar;45(4-5):352-5. doi: 10.1016/j.clinbiochem.2011.12.006. Epub 2011 Dec 19.

  PMID: 22200563 BACKGROUND

• Leung LY, Chan CP, Leung YK, Jiang HL, Abrigo JM, Wang de F, Chung JS, Rainer TH, Graham CA. Comparison of miR-124-3p and miR-16 for early diagnosis of hemorrhagic and ischemic stroke. Clin Chim Acta. 2014 Jun 10;433:139-44. doi: 10.1016/j.cca.2014.03.007. Epub 2014 Mar 17.

  PMID: 24650689 BACKGROUND

Biospecimen

Retention: SAMPLES WITH DNA

Liquid biopsy samples will be taken at three time intervals between stroke onset (Time 0) and 36 hours later i.e. i) in the ED at 0+x hours; ii) at 18±6 hours, and iii) 30±6 hours. Liquid biopsy for retention: • Whole Blood samples, Red blood cell effluent, Plasma, Serum, White cell pellet, Saliva (for genomic, epigenomic, transcriptomic and proteomic studies). Biomarkers under investigation: • DNA, RNA, Proteomics, Metabolomics, Metabolomics,Lipidomics gene expression in peripheral blood and saliva.

MeSH Terms

Conditions

Ischemic Stroke; Hemorrhagic Stroke; Ischemic Attack, Transient; Embolic Stroke; Embolism; Thrombosis; Atrial Fibrillation; Infarction, Anterior Cerebral Artery; Infarction, Middle Cerebral Artery; Stroke

Condition Hierarchy (Ancestors)

Cerebrovascular Disorders; Brain Diseases; Central Nervous System Diseases; Nervous System Diseases; Vascular Diseases; Cardiovascular Diseases; Brain Ischemia; Embolism and Thrombosis; Arrhythmias, Cardiac; Heart Diseases; Pathologic Processes; Pathological Conditions, Signs and Symptoms; Cerebral Infarction; Brain Infarction; Cerebral Arterial Diseases; Intracranial Arterial Diseases; Infarction; Ischemia; Necrosis

Study Officials

• Timothy H Rainer, MD

  The University of Hong Kong

  PRINCIPAL INVESTIGATOR

Central Study Contacts

Timothy H Rainer, MD

CONTACT

+852 39176846; thrainer@hku.hk

Study Design

• Study Type: observational
• Observational Model: CASE CONTROL
• Time Perspective: PROSPECTIVE
• Target Duration: 1 Year
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Professor of Emergency Medicine

Study Record Dates

• First Submitted: February 25, 2022
• First Posted: March 29, 2022
• Study Start: May 1, 2022
• Primary Completion: May 30, 2025
• Study Completion: May 30, 2025
• Last Updated: June 3, 2024

Record last verified: 2024-05

Data Sharing

• IPD Sharing: Will not share

Locations

CN (1)