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Translational Immunodiagnostics in Stroke (TrImS) (TrImS)

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: NCT05300997
Recruitment Status : Not yet recruiting
First Posted : March 29, 2022
Last Update Posted : April 29, 2022
Sponsor:
Information provided by (Responsible Party):
Prof. Timothy Hudson RAINER, The University of Hong Kong

Brief Summary:

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

  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. 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. to derive biomarker platforms of models for early acute stroke detection, diagnosis, dynamics, differentiation, monitoring, prediction and prognosis
  4. to validate these models in independent and external datasets

Condition or disease Intervention/treatment
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 Diagnostic Test: Biomarker blood draw and saliva collection

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Study Type : Observational [Patient Registry]
Estimated Enrollment : 650 participants
Observational Model: Case-Control
Time Perspective: Prospective
Target Follow-Up Duration: 1 Year
Official Title: Translational Immunodiagnostics in Suspected Stroke (TrImS): A Two-centre, Pragmatic, Prospective, Observational Study
Estimated Study Start Date : May 1, 2022
Estimated Primary Completion Date : May 30, 2025
Estimated Study Completion Date : May 30, 2025

Group/Cohort Intervention/treatment
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
Three peripheral 10mL blood sample (if available) Three 1 - 3mL salivary samples (if available)

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

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

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

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

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




Primary Outcome Measures :
  1. Differentiation of stroke from non-stroke in patients with suspected stroke [ Time Frame: Up to 24 hours ]

    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.



Secondary Outcome Measures :
  1. Differentiation of Transient Ischaemic Attack (TIA) from Transient non-neurological events (TNE) in patients with suspected acute stroke [ Time Frame: Up to 24 hours ]
    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. TNE is migraine, seizure or syncope.

  2. Differentiation of acute ischaemic stroke(AIS) from haemorrhagic stroke(HS) in patients with suspected acute stroke before and after imaging [ Time Frame: Up to 24 hours ]
    AIS is defined as an acute infarct on CT/MRI. HS is defined as an acute haemorrhage on CT/MRI.

  3. Differentiation of AIS-LVAD from AIS-SVD from AIS-CE in patients with suspected acute stroke [ Time Frame: Up to 24 hours ]

    AIS-LVAD is defined as an acute infarct on CT/MRI due to large vessel artery disease. The cause is a local obstruction (usually thrombus) in a large vessel with atherosclerosis (typically the common or internal carotid arteries, vertebral artery and Circle of Willis) which is usually treated with thrombectomy.

    AIS-SVD is defined as an acute infarct on CT/MRI within 10 days of symptom onset due to small vessel disease. The cause is a local obstruction in smaller arteries (typically branches of the Circle of Willis, middle cerebral artery, vertebral artery and basilar arteries) for which thrombectomy is not indicated.

    AIS-CE is defined as an acute infarct on CT/MRI due to an embolism from elsewhere in the body e.g. the heart or an extracranial large vessel.


  4. Differentiation of stroke of known origin (AIS/HS) from cryptogenic stroke in patients with suspected acute stroke [ Time Frame: Up to 24 hours ]

    Stroke of known origin, including acute ischemic stroke (AIS) of known origin and haemorrhagic stroke (HS). AIS is defined as an acute infarct on CT/MRI. HS is defined as an acute haemorrhage on CT/MRI.

    The American College of Cardiology state, 'There is no universally accepted definition for cryptogenic stroke . . .Cryptogenic stroke is defined by TOAST as stroke not caused by large artery atherosclerosis, cardioembolism, and small vessel occlusion; cryptogenic stroke is also defined as a stroke of undetermined etiology due to two or more causes being identified, negative evaluation, or incomplete evaluation. . . cryptogenic stroke is a diagnosis of exclusion - it is an ischemic stroke with no identifiable etiology'.


  5. Differentiation of early stroke onset (<4.5 hours) from late stroke onset (>4.5 hours) [ Time Frame: Up to 24 hours ]
    Early AIS is defined as CT/MRI evidence of ischaemia within 4.5 hours of symptom onset.

  6. Mortality [ Time Frame: Up to 30-days ]
    Mortality is defined as all-cause, post-stroke.

  7. Post-stroke Rankin score [ Time Frame: Up to 90-days ]
    Post-stroke Rankin score is defined as a six-point scale where 1 is normal and 6 is death.

  8. Development of point-of-care biomarker platforms for classifying patients presenting with suspected acute stroke [ Time Frame: Up to 90-days ]
    An accurate biomarker platform is defined as a combination of biomarkers that achieve a high area under the curve (AUC >0.9) and either a high sensitivity (>95%) or a high specificity (>95%) for the differentiation of all above outcomes (outcome 1 to outcome 8).

  9. Post-stroke QALY score [ Time Frame: Up to 1 year ]
    QALY is defined as a Quality Adjusted Life Year. One QALY is one year of life lived in perfect health. One year of life lived in less than perfect health is <1 QALY.


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.



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.


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Ages Eligible for Study:   18 Years to 100 Years   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   Yes
Sampling Method:   Non-Probability Sample
Study Population
Suspected stroke patients presenting to emergency department within 24 hours of symptom onset.
Criteria

Inclusion Criteria:

  • 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)
    • Major surgery within three months prior to the index event

Exclusion Criteria:

  • Clear onset of acute symptoms >24 hours.

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): NCT05300997


Contacts
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Contact: Timothy H Rainer, MD +852 39176846 thrainer@hku.hk

Locations
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China
Hong Kong University
Hong Kong, China
Contact: Timothy H Rainer, MD    852 39176846    thrainer@hku.hk   
Sponsors and Collaborators
The University of Hong Kong
Investigators
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Principal Investigator: Timothy H Rainer, MD The University of Hong Kong
Publications:
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 León 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. Erratum in: Lancet. 2013 Feb 23;381(9867):628. AlMazroa, Mohammad A [added]; Memish, Ziad A [added].

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Responsible Party: Prof. Timothy Hudson RAINER, Professor of Emergency Medicine, The University of Hong Kong
ClinicalTrials.gov Identifier: NCT05300997    
Other Study ID Numbers: TrImS-RAINER-2021
First Posted: March 29, 2022    Key Record Dates
Last Update Posted: April 29, 2022
Last Verified: April 2022
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: No

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Studies a U.S. FDA-regulated Drug Product: No
Studies a U.S. FDA-regulated Device Product: No
Keywords provided by Prof. Timothy Hudson RAINER, The University of Hong Kong:
acute stroke
emergency medicine
diagnostics
molecular
genomics and transcriptomics
proteomics
Additional relevant MeSH terms:
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Stroke
Ischemic Stroke
Ischemic Attack, Transient
Hemorrhagic Stroke
Embolic Stroke
Infarction, Middle Cerebral Artery
Infarction, Anterior Cerebral Artery
Atrial Fibrillation
Thrombosis
Atherosclerosis
Ischemia
Cerebrovascular Disorders
Brain Diseases
Central Nervous System Diseases
Nervous System Diseases
Vascular Diseases
Cardiovascular Diseases
Arrhythmias, Cardiac
Heart Diseases
Pathologic Processes
Embolism and Thrombosis
Arteriosclerosis
Arterial Occlusive Diseases
Brain Ischemia
Cerebral Infarction
Brain Infarction
Cerebral Arterial Diseases
Intracranial Arterial Diseases
Infarction
Necrosis