Degradation of the Glycocalyx in Delayed Cerebral Ischemia After Aneurysmal Subarachnoid Hemorrhage
2019年4月23日 更新者：Danny Theodore, MD、University of Virginia
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.
研究概览
详细说明
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]
研究类型
介入性
注册 (预期的)
42
阶段
- 不适用
联系人和位置
本节提供了进行研究的人员的详细联系信息，以及有关进行该研究的地点的信息。
学习地点
-
-
Virginia
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Charlottesville、Virginia、美国、22908
- 招聘中
- University of Virginia Health System
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接触：
- Marcia E Birk
-
-
参与标准
研究人员寻找符合特定描述的人，称为资格标准。这些标准的一些例子是一个人的一般健康状况或先前的治疗。
资格标准
适合学习的年龄
18年 及以上 (成人、年长者)
接受健康志愿者
不
有资格学习的性别
全部
描述
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
学习计划
本节提供研究计划的详细信息，包括研究的设计方式和研究的衡量标准。
研究是如何设计的？
设计细节
- 主要用途：其他
- 分配：不适用
- 介入模型：单组作业
- 屏蔽：无（打开标签）
武器和干预
参与者组/臂 |
干预/治疗 |
|---|---|
|
其他：Glycocalyx
degree of glycocalyx breakdown in patients with aSAH
|
Measure Degradation of the Glycocalyx
|
研究衡量的是什么？
主要结果指标
结果测量 |
措施说明 |
大体时间 |
|---|---|---|
|
Syndecan-1 and heparin sulfate
大体时间：day 0 through day 13
|
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
|
次要结果测量
结果测量 |
措施说明 |
大体时间 |
|---|---|---|
|
serum Matrix metalloproteinase-1 and Matrix metalloproteinase-9
大体时间：day 0 through day 13
|
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)
大体时间：day 0 through day13
|
urinary microalbumin-to-creatinine ratio (MACR) will be measured as it is marker of systemic damage to the glycocalyx
|
day 0 through day13
|
合作者和调查者
在这里您可以找到参与这项研究的人员和组织。
调查人员
- 首席研究员：Daniel Theodore, MD、University of Virginia
出版物和有用的链接
负责输入研究信息的人员自愿提供这些出版物。这些可能与研究有关。
一般刊物
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- Collins SR, Blank RS, Deatherage LS, Dull RO. Special article: the endothelial glycocalyx: emerging concepts in pulmonary edema and acute lung injury. Anesth Analg. 2013 Sep;117(3):664-674. doi: 10.1213/ANE.0b013e3182975b85. Epub 2013 Jul 8.
- Yang Y, Schmidt EP. The endothelial glycocalyx: an important regulator of the pulmonary vascular barrier. Tissue Barriers. 2013 Jan 1;1(1):e23494. doi: 10.4161/tisb.23494.
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- Ince C, Mayeux PR, Nguyen T, Gomez H, Kellum JA, Ospina-Tascon GA, Hernandez G, Murray P, De Backer D; ADQI XIV Workgroup. THE ENDOTHELIUM IN SEPSIS. Shock. 2016 Mar;45(3):259-70. doi: 10.1097/SHK.0000000000000473.
- Bell JD, Rhind SG, Di Battista AP, Macdonald RL, Baker AJ. Biomarkers of Glycocalyx Injury are Associated with Delayed Cerebral Ischemia Following Aneurysmal Subarachnoid Hemorrhage: A Case Series Supporting a New Hypothesis. Neurocrit Care. 2017 Jun;26(3):339-347. doi: 10.1007/s12028-016-0357-4.
- Lipowsky HH. The endothelial glycocalyx as a barrier to leukocyte adhesion and its mediation by extracellular proteases. Ann Biomed Eng. 2012 Apr;40(4):840-8. doi: 10.1007/s10439-011-0427-x. Epub 2011 Oct 8.
- Triglia T, Mezzapesa A, Martin JC, Verdier M, Lagier D, Dufour H, Bruder N, Alessi MC, Velly LJ. Early matrix metalloproteinase-9 concentration in the first 48 h after aneurysmal subarachnoid haemorrhage predicts delayed cerebral ischaemia: An observational study. Eur J Anaesthesiol. 2016 Sep;33(9):662-9. doi: 10.1097/EJA.0000000000000494.
- Tromp J, van der Pol A, Klip IT, de Boer RA, Jaarsma T, van Gilst WH, Voors AA, van Veldhuisen DJ, van der Meer P. Fibrosis marker syndecan-1 and outcome in patients with heart failure with reduced and preserved ejection fraction. Circ Heart Fail. 2014 May;7(3):457-62. doi: 10.1161/CIRCHEARTFAILURE.113.000846. Epub 2014 Mar 19.
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- Satoh M, Date I, Ohmoto T, Perkins E, Parent AD. The expression and activation of matrix metalloproteinase-1 after subarachnoid haemorrhage in rats. Acta Neurochir (Wien). 2005 Feb;147(2):187-92; discussion 192-3. doi: 10.1007/s00701-004-0435-9.
- Endo K, Takino T, Miyamori H, Kinsen H, Yoshizaki T, Furukawa M, Sato H. Cleavage of syndecan-1 by membrane type matrix metalloproteinase-1 stimulates cell migration. J Biol Chem. 2003 Oct 17;278(42):40764-70. doi: 10.1074/jbc.M306736200. Epub 2003 Aug 6.
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- Salmon AH, Satchell SC. Endothelial glycocalyx dysfunction in disease: albuminuria and increased microvascular permeability. J Pathol. 2012 Mar;226(4):562-74. doi: 10.1002/path.3964.
- Lee H, Park JW, Kim SP, Lo EH, Lee SR. Doxycycline inhibits matrix metalloproteinase-9 and laminin degradation after transient global cerebral ischemia. Neurobiol Dis. 2009 May;34(2):189-98. doi: 10.1016/j.nbd.2008.12.012. Epub 2009 Jan 6.
- Pires PW, Rogers CT, McClain JL, Garver HS, Fink GD, Dorrance AM. Doxycycline, a matrix metalloprotease inhibitor, reduces vascular remodeling and damage after cerebral ischemia in stroke-prone spontaneously hypertensive rats. Am J Physiol Heart Circ Physiol. 2011 Jul;301(1):H87-97. doi: 10.1152/ajpheart.01206.2010. Epub 2011 May 6.
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- Chaudhry K, Rogers R, Guo M, Lai Q, Goel G, Liebelt B, Ji X, Curry A, Carranza A, Jimenez DF, Ding Y. Matrix metalloproteinase-9 (MMP-9) expression and extracellular signal-regulated kinase 1 and 2 (ERK1/2) activation in exercise-reduced neuronal apoptosis after stroke. Neurosci Lett. 2010 Apr 26;474(2):109-14. doi: 10.1016/j.neulet.2010.03.020. Epub 2010 Mar 16.
研究记录日期
这些日期跟踪向 ClinicalTrials.gov 提交研究记录和摘要结果的进度。研究记录和报告的结果由国家医学图书馆 (NLM) 审查，以确保它们在发布到公共网站之前符合特定的质量控制标准。
研究主要日期
学习开始 (实际的)
2018年5月1日
初级完成 (预期的)
2020年5月1日
研究完成 (预期的)
2020年5月1日
研究注册日期
首次提交
2018年10月11日
首先提交符合 QC 标准的
2018年10月11日
首次发布 (实际的)
2018年10月16日
研究记录更新
最后更新发布 (实际的)
2019年4月25日
上次提交的符合 QC 标准的更新
2019年4月23日
最后验证
2019年4月1日
更多信息
此信息直接从 clinicaltrials.gov 网站检索，没有任何更改。如果您有任何更改、删除或更新研究详细信息的请求，请联系 register@clinicaltrials.gov. clinicaltrials.gov 上实施更改，我们的网站上也会自动更新.
动脉瘤性蛛网膜下腔出血的临床试验
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Wake Forest University Health SciencesNational Center for Advancing Translational Sciences (NCATS)完全的