Evaluation of the Level and Prognostic Relevance of New Neuroinflammation Markers in Subarachnoid Haemorrhage

NCT03411746 | Completed

• 1 other identifier: CE 115/17
• Study Type: observational
• Target: 60
• Locations: 1 country
• Sites: 1

Brief Summary

Subarachnoid hemorrhage (SAH) consists of blood extravasation into the space between arachnoid and pia mater. Bleeding is a consequence of cerebral aneurysm rupture in most cases. Despite incidence being only 9 cases out of 1000 people per year, young age and high mortality and morbidity lead to loosing several years of healthy life. Therapy priorities are: preventing rebleeding, with endovascular treatment (when possible) or neurosurgical aneurism clipping; preventing complications associated with blood extravasation into subarachnoid pace, such as acute hydrocephalus treatment (that occurs in 20% of patients), by ventricular external drainage positioning, and delayed cerebral ischemia, mainly due to vasospasm, by endovenous administration of nimodipine; optimal perfusion pressure maintenance. Endogenous osteopontin (OPN) is thought to fulfill a protective activity over ischemic damage both in brain and other organs, including kidney. Besides, recombinant OPN administration markedly decreases ischemic area in a focal cerebral ischemia model, by an antiapoptotic action. Recent in vivo studies on animal models of SAH demonstrated that OPN plays a major role: treatment with OPN seems to prevent vasospasm reducing smooth muscle cells and endothelial cells apoptosis. Microparticles are mediators released by platelets, leucocytes, erythrocyte and endothelial cells. In ischemic stroke endothelial microparticles levels directly relate to clinical severity and ischemic area extension. In typical parenchymal haemorrhage microparticles levels are higher both in blood and in liquor and associated with worse clinical outcome. In SAH increased microparticle levels have been demonstrated, especially in the days of the bleeding, and microparticle levels change based on subtypes. Data disagree about the subtypes involved and their time course. This study aims to evaluate the correlation between OPN and microparticles levels and vasospasm development/ischemic lesion at the CT-scan, and subsequently with medium and long-term patients outcome.

Conditions

Subarachnoid Hemorrhage

Outcome Measures

Primary Outcomes (1)

• Correlation between OPN and microparticle levels and vasospasm development/ischemic lesion at the CT-scan, and subsequently with medium and long-term patients outcome.

  The levels of OPN and microparticles will be related to: 1. the presence or absence of vasospasm development 2. the presence or absence of ischemic lesion at the CT-scan 3. 3-6 months outcome evaluated with the GOS-E

  Day 7 is the day expected for cerebral vasospasm. Therefore for the correlation between OPN/microparticles and vasospasm/ischemic lesion at CT scan will be evaluated on day 7.

Secondary Outcomes (1)

• In vitro stimulation of renal and pulmonary endothelial cells with microparticles

  Microparticles isolated from patient blood on the day of the expected maximum release, i.e., day 7 will be incubated in vitro with renal and pulmonary endothelial cells.

Other Outcomes (1)

• Levels of OPN in liquor and blood of patients with SAH

  Time course of OPN levels measured the day of bleeding and on days 1, 2, 3, 5, 7, 9, 11.

Interventions

Subarachnoid haemorrhage OTHER

Data on the type of patients enrolled have been described already in other sections.

Eligibility Criteria

• Age: 18 Years - 80 Years
• Sex: all
• Age Groups: Adult (18-64), Older Adult (65+)
• Sampling Method: Non-Probability Sample

Study Population

Patients with subarachnoid haemorrhage admitted to Neurosurgery or ICU of Ospedale Maggiore della Carita will be considered eligible, when meeting including criteria, within 24h from bleeding.

You may qualify if:

• Age between 18 and 80 years
• Subarachnoid haemorrhage from cerebral aneurysm rupture
• Indication to external liquor drainage

You may not qualify if:

• Age less than 18 or more than 80 years
• Bleeding occurred more than 24 hours before admission
• Known coagulopathies or antiplatelet or vitamin K antagonist treatment

Sponsors & Collaborators

• Azienda Ospedaliero Universitaria Maggiore della Carita: lead

Study Sites (1)

Rosanna Vaschetto

Novara, 28100, Italy

Location

Related Publications (4)

• Zhou C, Yamaguchi M, Colohan AR, Zhang JH. Role of p53 and apoptosis in cerebral vasospasm after experimental subarachnoid hemorrhage. J Cereb Blood Flow Metab. 2005 May;25(5):572-82. doi: 10.1038/sj.jcbfm.9600069.

  PMID: 15729295 BACKGROUND

• Schroeter M, Zickler P, Denhardt DT, Hartung HP, Jander S. Increased thalamic neurodegeneration following ischaemic cortical stroke in osteopontin-deficient mice. Brain. 2006 Jun;129(Pt 6):1426-37. doi: 10.1093/brain/awl094. Epub 2006 Apr 24.

  PMID: 16636021 BACKGROUND

• Huang M, Hu YY, Dong XQ. High concentrations of procoagulant microparticles in the cerebrospinal fluid and peripheral blood of patients with acute basal ganglia hemorrhage are associated with poor outcome. Surg Neurol. 2009 Nov;72(5):481-9; discussion 489. doi: 10.1016/j.surneu.2008.12.016. Epub 2009 Mar 27.

  PMID: 19328537 BACKGROUND

• Sanborn MR, Thom SR, Bohman LE, Stein SC, Levine JM, Milovanova T, Maloney-Wilensky E, Frangos S, Kumar MA. Temporal dynamics of microparticle elevation following subarachnoid hemorrhage. J Neurosurg. 2012 Sep;117(3):579-86. doi: 10.3171/2012.6.JNS111163. Epub 2012 Jul 13.

  PMID: 22794324 BACKGROUND

Biospecimen

Retention: SAMPLES WITHOUT DNA

plasma, serum, urine, liquor

MeSH Terms

Conditions

Subarachnoid Hemorrhage

Condition Hierarchy (Ancestors)

Intracranial Hemorrhages; Cerebrovascular Disorders; Brain Diseases; Central Nervous System Diseases; Nervous System Diseases; Vascular Diseases; Cardiovascular Diseases; Hemorrhage; Pathologic Processes; Pathological Conditions, Signs and Symptoms

Study Officials

• Rosanna Vaschetto, Professor

  Università degli Studi del Piemonte Orientale Amedeo Avogadro

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: observational
• Observational Model: CASE ONLY
• Time Perspective: PROSPECTIVE
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Prof.

Study Record Dates

• First Submitted: January 4, 2018
• First Posted: January 26, 2018
• Study Start: January 26, 2018
• Primary Completion: January 30, 2019
• Study Completion: July 31, 2019
• Last Updated: February 1, 2023

Record last verified: 2023-01

Data Sharing

• IPD Sharing: Will not share

Locations

IT (1)