Clinical trial NCT03706768: Degradation of the Glycocalyx in Delayed Cerebral Ischemia After Aneurysmal Subarachnoid Hemorrhage
Official title: Degradation of the Glycocalyx in Delayed Cerebral Ischemia After Aneurysmal Subarachnoid Hemorrhage
Study type: INTERVENTIONAL
Overall status: UNKNOWN
Phase: NA
Conditions: Aneurysmal Subarachnoid Hemorrhage
Lead sponsor: University of Virginia
Sponsor class: OTHER
First posted: 2018-10-16
Enrollment: 42
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
Intervention model description: Aneurysmal Subarachnoid Hemorrhage
Primary purpose: OTHER

Brief summary: 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: 1. 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:
2. Measurement of serum syndecan-1 by ELISA
3. Measurement of serum heparan-sulfate by ELISA
4. Measurement of serum matrix metalloproteinases -9
5. Measurement of serum matrix-metalloproteinase-1
6. Measurement of urinary microalbumin-to-creatinine ratio
7. Measurement of daily TCDs (all patients currently receive daily TCDs as part of the aSAH protocol at UTMCK and UVA Hospital)
8. 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 \[31\]

Eligibility criteria: 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

Primary outcomes:
measure: Syndecan-1 and heparin sulfate
timeFrame: day 0 through day 13
Secondary outcomes:
measure: serum Matrix metalloproteinase-1 and Matrix metalloproteinase-9
timeFrame: day 0 through day 13
measure: urinary microalbumin-to-creatinine ratio (MACR)
timeFrame: day 0 through day13
Other outcomes:
Locations:
city: Charlottesville
country: United States
facility: University of Virginia Health System
state: Virginia
Study officials:
affiliation: University of Virginia
name: Daniel Theodore, MD
role: PRINCIPAL_INVESTIGATOR
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