Ignite Creation Date:
2024-05-06 @ 7:37 PM
Last Modification Date:
2024-10-26 @ 3:10 PM
Study NCT ID:
NCT06078215
Status:
RECRUITING
Last Update Posted:
2023-10-13
First Post:
2023-10-05
Brief Title:
CERebrolysine Effect on Blood-brain Barrier in acUte Ischemic Stroke
Sponsor:
Poznan University of Medical Sciences
Organization:
Poznan University of Medical Sciences
Study Overview
Official Title:
CERebrolysine Effect on Blood-brain Barrier Endothelium Integrity During Reperfusion Therapy of acUte Ischemic Stroke CERBERUS Study
Status:
RECRUITING
Status Verified Date:
2023-10
Last Known Status:
None
Delayed Posting:
No
If Stopped, Why?:
Not Stopped
Has Expanded Access:
False
If Expanded Access, NCT#:
N/A
Has Expanded Access, NCT# Status:
N/A
Acronym:
CERBERUS
Brief Summary:
The study investigates whether Cerebrolysin stabilizes blood-brain barrier integrity in a manner that can be monitored using serum levels of the principal tight junction proteins eg occludin OCL claudin-5 CLN and zonula occludens-1 ZO-1 or other molecules known to be involved in BBB degradation eg S100B and whether it protects against hemorrhagic transformation in ischemic stroke patients after reperfusion therapy ie thrombolysis andor mechanical thrombectomy
Detailed Description:
Hemorrhagic transformation HT of ischemic stroke can be identified in 3-40 of patients The incidence varies depending on the definition used and the studied population The severity of HT can be described using clinical and radiological tools and classified as asymptomaticsymptomatic according to European Cooperative Acute Stroke Study classification and Heidelberg Bleeding Classification Breakdown of the blood-brain barrier BBB is associated with an increased risk of developing a hemorrhagic transformation HT of ischemic stroke In patients who received reperfusion therapy thrombolysis mechanical thrombectomy secondary HT had a negative influence on the clinical course and outcome
Tight junction TJ proteins are important cell adhesion components that stabilize endothelium cells lining and are responsible for maintaining the BBB integrity
Biomarkers of BBB damage that can be evaluated during the early phases of stroke might be useful for predicting the risk of HT Such biomarkers could also facilitate the decision of whether to begin thrombolytic therapy in acute ischemic stroke patients Experimental data support the evidence for protective effect of Cerebrolysin on BBB integrity Moreover it diminished and reversed negative effect of recombinant tissue plasminogen activator rtPA used as thrombolytic agent on endothelial cells integrity Cerebrolysin stabilized tight junction proteins expression occludin claudin-5 and zona occludens 1 ZO1 In our previous study we have found that circulating TJs predict HT in ischemic stroke patients Clinically evident HTs were associated with increased concentrations of occludin and S100B an increase in the claudin-5ZO-1 ratio and a decreased level of vascular endothelial growth factor VEGF Claudin-5 levels also correlated with HT occurrence when estimated within 3 hours of stroke onset The protective effects of Cerebrolysin were already clinically evidenced however there are no available studies using biomarkers of BBB
Aim of the study
We aim to investigate whether Cerebrolysin stabilizes BBB integrity in a manner that can be monitored using serum levels of the principal TJ proteins eg occludin OCL claudin-5 CLN and zonula occludens-1 ZO-1 or other molecules known to be involved in BBB degradation eg S100B and whether it protects against HT in ischemic stroke patients after reperfusion therapy
Study design
A prospective longitudinal study will be performed in ischemic stroke patients who
1 are included for reperfusion therapy intravenous thrombolysis andor mechanical thrombectomy - control group A
2 are included for reperfusion therapy intravenous thrombolysis andor mechanical thrombectomy plus Cerebrolysin group B
3 are not referred to reperfusion therapy nor Cerebrolysin group C
All patients with NIHSS score 8 will receive 30 ml Cerebrolysin in 500 ml of buffered crystalloid solution intravenously initiated within 12 hours from symptoms onset
Whole blood samples will be withdrawn at the admission then within 1 to 3 days after stroke onset and at 7th day after stroke onset or when the endpoint will be reached by the patient Occludin claudin 5 and ZO-1 concentrations will be analyzed by means of home-made enzyme-linked immunosorbent assay
Endpoint will include clinical worsening increase in the NIHSS by 4 points radiologically evident hemorrhage or radiologically evident brain edema at control CT performed within 1 to 3 days after stroke onset
Standard head CT will be performed in all patients at the admission within 1 to 3 days after stroke onset after worsening of clinical status and additionally when the differentiation between hemorrhage and contrast staining will be required in thrombectomy patients Hemorrhagic transformation of ischemic stroke will be classified according to Table 1
Clinimetric evaluation of all patients will include NIHSS every day for 7 days and at day 30 Modified Rankin scale mRS will be evaluated at visit 1234 and 5 Barthel index at visit 4 and 5 and Montreal Cognitive Assessment Test at visit 5
All patents will undergo current American Heart Association Guidelines for the Early Management of Patients with Acute Ischemic Stroke
Expected results It is expected that Cerebrolysin can stabilize blood-brain barrier in ischemic stroke patients treated with reperfusion therapies via remodelling of tight junction proteins between endothelial cells Such an effect measured by the levels of circulating tight junction proteins can translate into prevention of hemorrhagic transformation To summarize Cerebrolysine can guard blood-brain barrier integrity in ischemic stroke Cerberus effect
Tight junction TJ proteins are important cell adhesion components that stabilize endothelium cells lining and are responsible for maintaining the BBB integrity
Biomarkers of BBB damage that can be evaluated during the early phases of stroke might be useful for predicting the risk of HT Such biomarkers could also facilitate the decision of whether to begin thrombolytic therapy in acute ischemic stroke patients Experimental data support the evidence for protective effect of Cerebrolysin on BBB integrity Moreover it diminished and reversed negative effect of recombinant tissue plasminogen activator rtPA used as thrombolytic agent on endothelial cells integrity Cerebrolysin stabilized tight junction proteins expression occludin claudin-5 and zona occludens 1 ZO1 In our previous study we have found that circulating TJs predict HT in ischemic stroke patients Clinically evident HTs were associated with increased concentrations of occludin and S100B an increase in the claudin-5ZO-1 ratio and a decreased level of vascular endothelial growth factor VEGF Claudin-5 levels also correlated with HT occurrence when estimated within 3 hours of stroke onset The protective effects of Cerebrolysin were already clinically evidenced however there are no available studies using biomarkers of BBB
Aim of the study
We aim to investigate whether Cerebrolysin stabilizes BBB integrity in a manner that can be monitored using serum levels of the principal TJ proteins eg occludin OCL claudin-5 CLN and zonula occludens-1 ZO-1 or other molecules known to be involved in BBB degradation eg S100B and whether it protects against HT in ischemic stroke patients after reperfusion therapy
Study design
A prospective longitudinal study will be performed in ischemic stroke patients who
1 are included for reperfusion therapy intravenous thrombolysis andor mechanical thrombectomy - control group A
2 are included for reperfusion therapy intravenous thrombolysis andor mechanical thrombectomy plus Cerebrolysin group B
3 are not referred to reperfusion therapy nor Cerebrolysin group C
All patients with NIHSS score 8 will receive 30 ml Cerebrolysin in 500 ml of buffered crystalloid solution intravenously initiated within 12 hours from symptoms onset
Whole blood samples will be withdrawn at the admission then within 1 to 3 days after stroke onset and at 7th day after stroke onset or when the endpoint will be reached by the patient Occludin claudin 5 and ZO-1 concentrations will be analyzed by means of home-made enzyme-linked immunosorbent assay
Endpoint will include clinical worsening increase in the NIHSS by 4 points radiologically evident hemorrhage or radiologically evident brain edema at control CT performed within 1 to 3 days after stroke onset
Standard head CT will be performed in all patients at the admission within 1 to 3 days after stroke onset after worsening of clinical status and additionally when the differentiation between hemorrhage and contrast staining will be required in thrombectomy patients Hemorrhagic transformation of ischemic stroke will be classified according to Table 1
Clinimetric evaluation of all patients will include NIHSS every day for 7 days and at day 30 Modified Rankin scale mRS will be evaluated at visit 1234 and 5 Barthel index at visit 4 and 5 and Montreal Cognitive Assessment Test at visit 5
All patents will undergo current American Heart Association Guidelines for the Early Management of Patients with Acute Ischemic Stroke
Expected results It is expected that Cerebrolysin can stabilize blood-brain barrier in ischemic stroke patients treated with reperfusion therapies via remodelling of tight junction proteins between endothelial cells Such an effect measured by the levels of circulating tight junction proteins can translate into prevention of hemorrhagic transformation To summarize Cerebrolysine can guard blood-brain barrier integrity in ischemic stroke Cerberus effect
Study Oversight
Has Oversight DMC:
None
Is a FDA Regulated Drug?:
False
Is a FDA Regulated Device?:
False
Is an Unapproved Device?:
None
Is a PPSD?:
None
Is a US Export?:
None
Is an FDA AA801 Violation?:
None