MicroRNA Diagnostics in Subarachnoid Hemorrhage 2

Study Overview
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Brief Summary
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The purpose of this study is to validate results from a related trial (NCT01791257) and to compare the profile of microRNA in blood from patients suffering subarachnoid hemorrhage with and without systemic complications.

Detailed Description
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In this study of patients suffering an aneurysmal subarachnoid hemorrhage (SAH) we would like to validate former results from CSF studies through microRNA profiling investigate the pathophysiological mechanisms that lead to systemic complications such as cardiac dysfunction, acute lung injury (ALI) and systemic inflammatory response syndrome(SIRS). We will accomplish this through analyzing the profile of microRNA expression in blood and cerebrospinal fluid from SAH patients. Validation: As in our earlier study we wish to compare the expression of 20 specific microRNA between 12 patients developing DCI (group 1) and 12 patients without DCI (group 2) in cerebrospinal fluid drawn on day 5 after ictus. In addition, some of the patients will have established invasive neuromonitoring including microdialysis in which we will study changes of certain microRNAs. DCI as defined by Vergouwen et al in Stroke 2010;41(10):2391-2395: The occurrence of focal neurological impairment (such as hemiparesis, aphasia, apraxia, hemianopia, or neglect), or a decrease of at least 2 points on the Glasgow Coma Scale (either on the total score or on one of its individual components [eye, motor on either side, verbal]). This should last for at least 1 hour, is not apparent immediately after aneurysm occlusion, and cannot be attributed to other causes by means of clinical assessment, CT or MRI scanning of the brain, and appropriate laboratory studies. Systemic complications: Furthermore, we wish to compare the expression of 754 specific microRNA in blood drawn on day 3 after ictus between patients with ALI (as described Kahn et al, Crit Care Med. 2006; 34: 196-202) and patients without ALI. Of at least 36 patients expected to be included 12 should statistically develop ALI according to the referred definition. Additionally, we wish to compare the expression of 754 specific microRNA between 12 patients developing DCI (group 1) and 12 patients without DCI (group 2) in blood drawn on day 3 after ictus. Moreover, we wish to compare the expression of 754 specific microRNA in blood between 36 patients (group 1-3) to that of healthy controls. The specific microRNAs of interest in which the expression in blood between patients with systemic complication are analyzed daily to investigate the dynamic changes in expression and compared to the clinical course.

Official Title
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MicroRNA Diagnostics in Subarachnoid Hemorrhage 2

Conditions
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Subarachnoid Hemorrhage, Delayed Cerebral Ischemia, Acute Lung Injury, Cardiac Dysfunction, Systemic Inflammatory Response Syndrome

Participation Criteria
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Eligibility Criteria
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Inclusion Criteria Group 1-3: Uncertainty < 24 times on time of ictus Inclusion Criteria Group 1-2: Patients admitted to Neurointensive Department in Rigshospitalet with aneurysmal SAH treated with external ventricular drain. Inclusion Criteria Group 3: Patients admitted to Neurointensive Department in Rigshospitalet with aneurysmal SAH treated without external ventricular drain. Exclusion Criteria Group 1-3: Transfer to other hospital within 5 days of admission

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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Accepts Healthy Volunteers

Study Plan
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How is the study designed?
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Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| SAH with DCI<br>After 21 days from ictus the patients with subarachnoid hemorrhage are stratified to group 1 or 2 depending on their development of delayed cerebral ischemia. | |
| SAH without DCI<br>After 21 days from ictus the patients with subarachnoid hemorrhage are stratified to group 1 or 2 depending on their development of delayed cerebral ischemia. | |
| SAH good grade<br>SAH without external ventricular drainage | |
| Healthy controls<br>Blood sample in healthy donors registered in the National Donor Registry. | |

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Delayed Cerebral Ischemia | Delayed Cerebral Ischemia as defined by Vergouwen et al[1]. In our earlier study we found the clinical condition DCI somehow subjective which is why we added the following two primary outcome measures. Comparing microRNA profiles between groups with or without. | 21 days | 
| Delayed Cerebral Ischemia and Cerebral infarction | as defined by Vergouwen et al [1]. Comparing microRNA profiles between groups with or without. | 21 days | 
| Delayed Cerebral infarction | as defined by Vergouwen et al [1]. Comparing microRNA profiles between groups with or without. | 21 days | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Acute Lung Injury | as defined by Kahn et al[2]. Comparing microRNA profiles between groups with or without | 21 days | 
| Cardiac Dysfunction | Evaluated by transthoracic echocardiography Comparing microRNA profiles between groups with or without | 21 days | 
| Systemic Inflammatory Response Syndrome | Evaluated through daily vital signs and biochemistry Comparing microRNA profiles between groups with or without | 21 days | 
| Early Brain Injury | Early Brain injury = GCS 3-12 and/or paresis (degree 4) of at least one extremity or aphasia No Early Brain injury = GCS 13-15 and no or only small and mild focal deficit Comparing microRNA profiles between groups with or without | Clinical evaluation 24-72 hours after ictus. (Wake-up call if sedated) | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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MicroRNA, Cerebrospinal fluid