Monitoring of the Ischemic Stroke Patient Through the Use of New Serum Biomarkers and MRI Imaging

Aim of this study will be the evaluation (by ELISA quantification and quantitative RT-PCR) of circulating biomarkers of damage and regeneration in patients affected by ischemic stroke. The biomarker levels will be measured from the acute event (48h) and in subsequent 4 times (7 days, 30 days, 90 days, 180 days) following hospitalization, up to 6 months after the acute event. These data will then be correlated for all five times with the clinical scales normally used for patient evaluation and will also be associated with MRI-DTI measurements performed in the post-acute (30 days) and post-discharge (180 days) phase.

Study Overview

• Status: Completed
• Conditions: Stroke

Detailed Description

In current clinical practice, outcome's assessment after stroke and patients' monitoring during rehabilitation rely on scores in clinical scales and instrumental evaluations (electrophysiological evaluations and MRI imaging). This approach follows current guidelines but has some limitations:

• subjectivity of the patient's clinical evaluation and instrumental data's interpretation
• poor prognostic value of clinical scales;
• poor prognostic value of instrumental measurements;
• difficulty in standardizing and automating clinical/instrumental assessments;
• difficulty in evaluating medical services on a large scale due to the lack of discrete values of treatment efficacy.

The identification and validation of reliable and accessible biomarkers associated with patients' functional recovery could improve their care but still remains a clinical challenge.

Aim of this study will be to measure the levels of circulating biomarkers of brain damage and regeneration in patients affected by ischemic stroke, and to evaluate their prognostic relevance over a 6-month follow-up. Biomarkers' levels will be measured by ELISA and quantitative RT-PCR from the acute event (within 24h from symptoms onset) and in subsequent 4 time-points (7 days, 30 days, 90 days, 180 days post-stroke). Obtained data will be correlated with clinical scales used for patient evaluation and will be associated with MRI-DTI measurements performed in the post-acute (30 days) and post-discharge (180 days) phase.

• Study Type: Observational
• Enrollment (Actual): 135

Contacts and Locations

Study Locations

• Italy
  • Lombardia
    • Pavia, Lombardia, Italy, 27100
      • Istituti Clinici Scientifici Maugeri SpA

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Adult; Older Adult
• Accepts Healthy Volunteers: No

• Sampling Method: Probability Sample

Study Population

Patients with minor/moderate/severe stroke

Description

Inclusion Criteria:

• First occurrence of brain injury, confirmed on CT imaging, determined by ischemic stroke
• Patient able to sign an informed consent, alternatively legal representative or relative

Exclusion Criteria:

• Previous ischemic events
• Previous head trauma of any entity
• New onset of acute events during the study
• Previous illness, diagnosis or suspicion of current illness with central nervous system involvement
• Diagnosis of cognitive impairment prior to the acute event (MMSE < 24)
• Need for walking assistance prior to the acute event
• Diagnosis of autoimmune diseases
• Diagnosis of haematological or oncological disease
• Diagnosis of a psychiatric condition: bipolar disorder, psychosis, schizophrenia or suicidal ideation
• Subjects with relative and absolute contraindications to magnetic resonance imaging.
• Life expectancy less than 1 year
• Dependence or abuse of alcohol, drugs or psychotropics prior to the acute event
• Pregnancy in progress
• Severe renal or hepatic insufficiency (Renal disease > II stage, Child-Plugh score >5)

Study Plan

How is the study designed?

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Circulating/neuroimaging biomarkers and GCS	Correlation between circulating/neuroimaging biomarkers (GFAP as the only biomarker of brain damage, BDNF and VEGF as markers of neuronal regeneration and plasticity) and functional recovery expressed by Glasgow Coma Scale (GCS)	54 months
Circulating/neuroimaging biomarkers and NIHSS	Correlation between circulating/neuroimaging biomarkers (GFAP as the only biomarker of brain damage, BDNF and VEGF as markers of neuronal regeneration and plasticity) and functional recovery expressed by NIHSS scale	54 months
Circulating/neuroimaging biomarkers and mRS	Correlation between circulating/neuroimaging biomarkers (GFAP as the only biomarker of brain damage, BDNF and VEGF as markers of neuronal regeneration and plasticity) and functional recovery expressed by modified Rankin Scale (mRS)	54 months
Circulating/neuroimaging biomarkers and Functional Ambulation Classification	Correlation between circulating/neuroimaging biomarkers (GFAP as the only biomarker of brain damage, BDNF and VEGF as markers of neuronal regeneration and plasticity) and functional recovery expressed by Functional Ambulation Classification	54 months
Circulating/neuroimaging biomarkers and Ashworth scale	Correlation between circulating/neuroimaging biomarkers (GFAP as the only biomarker of brain damage, BDNF and VEGF as markers of neuronal regeneration and plasticity) and functional recovery expressed by Ashworth scale	54 months
Circulating/neuroimaging biomarkers and MMSE	Correlation between circulating/neuroimaging biomarkers (GFAP as the only biomarker of brain damage, BDNF and VEGF as markers of neuronal regeneration and plasticity) and functional recovery expressed by MMSE scale	54 months

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Biomarker curve trend	Estimation of the impact of rehabilitation treatment on the trend of the biomarker curve in patients with ischemic stroke, i.e. how GFAP changes in time after treatment (comparison of GFAP levels between times)	54 months

Collaborators and Investigators

• Sponsor: Istituti Clinici Scientifici Maugeri SpA

Study record dates

Study Major Dates

• Study Start (Actual): December 4, 2018
• Primary Completion (Actual): June 3, 2023
• Study Completion (Actual): June 3, 2023

Study Registration Dates

• First Submitted: March 8, 2023
• First Submitted That Met QC Criteria: March 31, 2023
• First Posted (Actual): April 14, 2023

Study Record Updates

• Last Update Posted (Actual): July 21, 2023
• Last Update Submitted That Met QC Criteria: July 20, 2023
• Last Verified: March 1, 2023

More Information

Terms related to this study

• Keywords: stroke; biomarkers
• Additional Relevant MeSH Terms: Cardiovascular Diseases; Vascular Diseases; Cerebrovascular Disorders; Brain Diseases; Central Nervous System Diseases; Nervous System Diseases; Stroke; Ischemic Stroke
• Other Study ID Numbers: 2250

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No