Degradation of the Glycocalyx in Delayed Cerebral Ischemia After Aneurysmal Subarachnoid Hemorrhage

Study Overview
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Brief Summary
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This study will provide novel information to the literature base for the pathophysiology of aneurysmal subarachnoid hemorrhage. The association of breakdown products in the serum of aSAH patients were reported in a very small case series of 3 patients, as mentioned above. However, while their results are intriguing and encouraging, our study will provide more definitive information about the GC in aSAH. If there is a positive correlation, the results of this study will guide future investigations into new therapies for this devastating disease such as MMP inhibition with doxycycline.

Detailed Description
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The study will aim to recruit all eligible patients at UTMCK and the University of Virginia hospital over a 12 month period. Our main outcome measure is degradation of the glycocalyx in patients with aSAH. All eligible patients with confirmed aSAH admitted to the neuro-intensive care unit will be enrolled after consent is obtained from the family and/or the patient. Serum samples will be drawn from each patient on admission (day 1) and every other day until day 13 for a total of 7 samples per patient. The following serum tests will be performed: Measurement of serum syndecan-1 by ELISA Measurement of serum heparan-sulfate by ELISA Measurement of serum matrix metalloproteinases -9 Measurement of serum matrix-metalloproteinase-1 Measurement of urinary microalbumin-to-creatinine ratio Measurement of daily TCDs (all patients currently receive daily TCDs as part of the aSAH protocol at UTMCK and UVA Hospital) Outcomes: a) Chart review: i) Incidence of DCI as defined by a consensus committee on this subject and published in the journal Stroke [29]. ii) In-hospital mortality will be recorded b) Follow-up performed by phone call or searching the Social Security Death Index [30]: i) 30-day mortality ii) 90-day mortality c) Outcomes follow-up: i) The Glasgow Outcome Scale 12 weeks post aSAH [31]

Official Title
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Degradation of the Glycocalyx in Delayed Cerebral Ischemia After Aneurysmal Subarachnoid Hemorrhage

Conditions
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Aneurysmal Subarachnoid Hemorrhage

Intervention / Treatment
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* Other: Glycocalyx


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: • Age 18 years of age and older Cerebral aneurysm on CT-angio Exclusion Criteria: • comfort care only orders, the absence of an aneurysm on CT-angiography, onset of aneurysm rupture > 24 hours, and inability to obtain informed consent from patient or family pregnant women

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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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Other
Intervention Model: Single Group Assignment
Interventional Model Description: Aneurysmal Subarachnoid Hemorrhage
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Other: Glycocalyx<br>degree of glycocalyx breakdown in patients with aSAH | Other: Glycocalyx<br>* Measure Degradation of the Glycocalyx<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Syndecan-1 and heparin sulfate | Compare the degree of glycocalyx breakdown in patients with aSAH who develop delayed cerebral ischemia (DCI) to those that do not develop DCI. This will be completed by measuring the breakdown of Syndecan-1 and heparin sulfate in the blood. | day 0 through day 13 | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| serum Matrix metalloproteinase-1 and Matrix metalloproteinase-9 | serum MMP-9 and MMP-1 will be levels will be measured as serum MMP concentrations have been positively correlated with the incidence of delayed cerebral ishemia | day 0 through day 13 | 
| urinary microalbumin-to-creatinine ratio (MACR) | urinary microalbumin-to-creatinine ratio (MACR) will be measured as it is marker of systemic damage to the glycocalyx | day 0 through day13 |