CERebrolysine Effect on Blood-brain Barrier in acUte Ischemic Stroke

NCT06078215 | Unknown Phase 4

• 1 other identifier: 392/2023
• Study Type: interventional
• Target: 350
• Locations: 1 country
• Sites: 1

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, e.g., occludin (OCL), claudin-5 (CLN), and zonula occludens-1 (ZO-1), or other molecules known to be involved in BBB degradation, e.g., S100B and whether it protects against hemorrhagic transformation in ischemic stroke patients after reperfusion therapy (i.e. thrombolysis and/or mechanical thrombectomy).

Conditions

Acute Ischemic Stroke

Keywords

Acute Ischemic Stroke; blood-brain barrier; cerebrolysin

Outcome Measures

Primary Outcomes (9)

• National Institute of Health Stroke Scale

  National Institute of Health Stroke Scale; score range: 1-42; 1-4 - Minor stroke; 5-15 - Moderate stroke; 16-20 - Moderate to severe stroke; 21-42 - Severe stroke

  every day for 7 days after stroke onset

• National Institute of Health Stroke Scale

  National Institute of Health Stroke Scale; score range: 1-42; 1-4 - Minor stroke; 5-15 - Moderate stroke; 16-20 - Moderate to severe stroke; 21-42 - Severe stroke

  at day 30 after stroke onset

• Detection of hemorrhagic transformation [range o:1]

  hemorrhagic transformation on head computerized tomography

  within 1 to 3 days after stroke onset, after worsening of clinical status by more than 4 points in NIHSS

• Concentration of plasma occludin [ng/mL]

  Occludin is an enzyme (EC 1.6) that oxidizes NADH (Nicotinamide adenine dinucleotide)

  at the admission, within 1 to 3 days after stroke onset

• Concentration of plasma occludin [ng/mL]

  Occludin is an enzyme (EC 1.6) that oxidizes NADH (Nicotinamide adenine dinucleotide)

  at 7th day after stroke onset

• Concentration of plasma claudin 5 [ng/mL]

  Claudins are small (20-24/27 kilodalton (kDa)) transmembrane proteins.

  at the admission, within 1 to 3 days after stroke onset

• Concentration of plasma claudin 5 [ng/mL]

  Claudins are small (20-24/27 kilodalton (kDa)) transmembrane proteins.

  at 7th day after stroke onset

• Concentration of plasma ZO1 [ng/mL]

  Zonula occludens-1 ZO-1, also known as Tight junction protein-1

  at the admission, within 1 to 3 days after stroke onset

• Concentration of plasma ZO1 [ng/mL]

  Zonula occludens-1 ZO-1, also known as Tight junction protein-1

  at 7th day after stroke onset

Secondary Outcomes (8)

• Modified Rankin scale [range 0:6]

  at the admission, within 1 to 3 days after stroke onset

• Modified Rankin scale [range 0:6]

  at 7th day after stroke onset

• Modified Rankin scale [range 0:6]

  at the 30th +/- 5 day after stroke onset

• Modified Rankin scale [range 0:6]

  at 90th +/- 5 day after stroke onset

• Barthel Index for Activities of Daily Living (ADL) [range 0:100]

  30th +/- 5 day after stroke onset

Study Arms (3)

Thrombolysis and/or mechanical thrombectomy

NO INTERVENTION

patients included for reperfusion therapy (intravenous thrombolysis and/or mechanical thrombectomy - comparator

Cerebrolysin

EXPERIMENTAL

patients included for reperfusion therapy (intravenous thrombolysis and/or mechanical thrombectomy and treated with Cerebrolysin

Combination Product: Cerebrolysin

No reperfusion therapy / no cerebrolysin

NO INTERVENTION

patients not referred to reperfusion therapy nor Cerebrolysin

Interventions

Cerebrolysin COMBINATION_PRODUCT

Intravenous infusion of 30 ml Cerebrolysine in 500 ml of buffered crystalloid solution intravenously initiated within 12 hours from symptoms onset

Also known as: FPF (Fine Particle Fraction)-1070

Cerebrolysin

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• acute ischemic stroke patients
• informed consent

You may not qualify if:

• no informed consent
• primary or metastatic brain tumor
• brain abscess
• encephalitis
• localized inflammation
• sepsis
• autoimmune diseases of central or peripheral nervous system
• Cerebrolysin hypersensitivity / allergy
• epilepsy
• severe kidney disease

Sponsors & Collaborators

• Poznan University of Medical Sciences: lead

Study Sites (1)

University Hospital

Poznan, 60-355, Poland

RECRUITING

Related Publications (6)

• Kazmierski R, Michalak S, Wencel-Warot A, Nowinski WL. Serum tight-junction proteins predict hemorrhagic transformation in ischemic stroke patients. Neurology. 2012 Oct 16;79(16):1677-85. doi: 10.1212/WNL.0b013e31826e9a83. Epub 2012 Sep 19.

  PMID: 22993287 BACKGROUND

• Poljakovic Z, Supe S, Ljevak J, Starcevic K, Peric I, Blazevic N, Krbot-Skoric M, Jovanovic I, Ozretic D. Efficacy and safety of Cerebrolysin after futile recanalisation therapy in patients with severe stroke. Clin Neurol Neurosurg. 2021 Aug;207:106767. doi: 10.1016/j.clineuro.2021.106767. Epub 2021 Jun 18.

  PMID: 34214867 BACKGROUND

• Teng H, Li C, Zhang Y, Lu M, Chopp M, Zhang ZG, Melcher-Mourgas M, Fleckenstein B. Therapeutic effect of Cerebrolysin on reducing impaired cerebral endothelial cell permeability. Neuroreport. 2021 Mar 24;32(5):359-366. doi: 10.1097/WNR.0000000000001598.

  PMID: 33661804 BACKGROUND

• Kassner A, Roberts T, Taylor K, Silver F, Mikulis D. Prediction of hemorrhage in acute ischemic stroke using permeability MR imaging. AJNR Am J Neuroradiol. 2005 Oct;26(9):2213-7.

  PMID: 16219824 BACKGROUND

• Zhang Y, Chopp M, Zhang ZG, Zhang Y, Zhang L, Lu M, Zhang T, Winter S, Doppler E, Brandstaetter H, Mahmood A, Xiong Y. Cerebrolysin Reduces Astrogliosis and Axonal Injury and Enhances Neurogenesis in Rats After Closed Head Injury. Neurorehabil Neural Repair. 2019 Jan;33(1):15-26. doi: 10.1177/1545968318809916. Epub 2018 Nov 30.

  PMID: 30499355 BACKGROUND

• Lang W, Stadler CH, Poljakovic Z, Fleet D; Lyse Study Group. A prospective, randomized, placebo-controlled, double-blind trial about safety and efficacy of combined treatment with alteplase (rt-PA) and Cerebrolysin in acute ischaemic hemispheric stroke. Int J Stroke. 2013 Feb;8(2):95-104. doi: 10.1111/j.1747-4949.2012.00901.x. Epub 2012 Sep 26.

  PMID: 23009193 BACKGROUND

MeSH Terms

Conditions

Ischemic Stroke

Interventions

cerebrolysin; Receptors, Tumor Necrosis Factor, Type I

Condition Hierarchy (Ancestors)

Stroke; Cerebrovascular Disorders; Brain Diseases; Central Nervous System Diseases; Nervous System Diseases; Vascular Diseases; Cardiovascular Diseases

Intervention Hierarchy (Ancestors)

Receptors, Death Domain; Receptors, Cell Surface; Membrane Proteins; Proteins; Amino Acids, Peptides, and Proteins; Receptors, Tumor Necrosis Factor; Receptors, Cytokine; Receptors, Immunologic

Study Officials

• Slawomir Michalak, Prof.

  Poznan University of Medical Sciences

  PRINCIPAL INVESTIGATOR

Central Study Contacts

Slawomir Michalak, Prof.

CONTACT

+48 61 8691 535; swami@ump.edu.pl

Joanna Rybacka-Mossakowska, MD, PhD

CONTACT

+48 61 8691 459; joannarybacka@gmail.com

Study Design

• Study Type: interventional
• Phase: phase 4
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Model Details: A prospective longitudinal study will be performed in ischemic stroke patients who: 1. are included for reperfusion therapy (intravenous thrombolysis and/or mechanical thrombectomy - control (group A), 2. are included for reperfusion therapy (intravenous thrombolysis and/or mechanical thrombectomy plus Cerebrolysin (group B) 3. are not referred to reperfusion therapy nor Cerebrolysin (group C).

Study Record Dates

• First Submitted: October 5, 2023
• First Posted: October 11, 2023
• Study Start: January 10, 2023
• Primary Completion: January 31, 2025
• Study Completion: March 31, 2025
• Last Updated: October 13, 2023

Record last verified: 2023-10

Data Sharing

• IPD Sharing: Will not share

Locations

PL (1)