Immunological Biomarkers in Patients With Acute Ischemic Stroke

Completed

• Conditions: Ischemic Stroke

• Registration Number: NCT01894529
• Lead Sponsor: Hospital Clinic of Barcelona

Brief Summary

Stroke is accompanied by local inflammatory response and systemic immunosuppression. Immunosuppression markers are associated with the occurrence of medical complications (infections), whereas inflammatory markers are associated with worse functional prognosis.

This prospective study tries to validate in acute stroke patients the prognostic usefulness of a panel of immune biomarkers that have previously been associated with various clinical outcomes.

The identification of beneficial and harmful immune responses in cerebral ischemia will allow the prediction of the clinical course of the patients and will be helpful in designing immunomodulatory therapeutic strategies for acute stroke.

Detailed Description

Stroke is accompanied by local inflammatory response and systemic immunosuppression. Immunosuppression markers are associated with the occurrence of medical complications (infections), whereas inflammatory markers are associated with worse functional prognosis.

This prospective study tries to validate in acute stroke patients the prognostic usefulness of a panel of immune biomarkers that have previously been associated with various clinical outcomes. The immune biomarkers will be assessed at admission, at day 1 after admission and at day 90. The assessed immune biomarker panel includes:

* Serum cortisol levels.

* Serum interleukin (IL)-10 levels.

* Proportion of circulating B lymphocytes (CD3-CD19+ cells).

* Monocyte surface expression of TLR4, HLA-DR, CD86, and VLA-4.

* Ex - vivo production of tumor necrosis factor (TNF)-α in monocytes after stimulation with LPS.

* Proportion of each of the circulating monocyte subpopulations (CD14highCD16-, CD14highCD16+, and CD14dimCD16+).

The identification of beneficial and harmful immune responses in cerebral ischemia will allow the prediction of the clinical course of the patients and will be helpful in designing immunomodulatory therapeutic strategies for acute stroke.

Study Timeline

• Study Start: 2010-01
• Primary Completion: 2013-05
• Study Completion: 2013-05
• Study First Submitted: 2013-07-04
• Study First Submitted QC: 2013-07-04
• Study First Posted: 2013-07-10
• Status Verified: 2015-04
• Last Update Submitted: 2015-04-28
• Last Update Posted: 2015-04-29

Recruitment & Eligibility

• Status: COMPLETED
• Sex: All
• Target Recruitment: 132

Inclusion Criteria

• ischemic stroke*

• stroke onset within 6h*

• treated with systemic or intraarterial thrombolysis*

• minimum severity in the NIHSS of 3*

• age ≥ 18

• consent by the patient or the legal representative

  • These items do not apply for healthy subjects.

Exclusion Criteria

• intracranial hemorrhage
• signs of infection at admission
• use of antibiotics, immunosuppressors or corticosteroids in the previous 3 months
• significant disability (mRS>2) before index stroke

Study & Design

• Study Type: OBSERVATIONAL
• Study Design: Not specified

Primary Outcome Measures

Name	Time	Method
Predictive immune score for favorable outcome	90 +-15 days after onset of symptoms	To establish a predictive immune score for functional outcome. Favorable outcome is defined as a modified Rankin Scale (mRS) score of \<3 at day 90+-15 after stroke
Predictive immune score for stroke associated infection	7 days after onset of symptoms	To establish a predictive score for stroke associated infection (SAI) based on immune biomarkers. Stroke associated infection is defined as: body temperature \> 37.7ºC and symptoms of infection (cough, dyspnea, pleuritic pain, dysuria), or leukocytosis \>11000, leukopenia \<4000, pulmonary infiltrates in chest X-ray or positive cultures for a pathogen.

Secondary Outcome Measures

Name	Time	Method
Localization and stroke volume analysis	SAI within 7 days and neurological outcome after 3 months after onset of symptoms	To investigate the influence of the localization and stroke volume on the occurrence of a stroke associated infection and on neurological outcome
Thrombolysis, immune biomarkers and SAI	SAI within 7 days after onset of symptoms	To assess the effect of thrombolytic treatment over changes in the immune biomarker panel and over the occurrence of SAI
Infection and functional outcome after ischemic stroke	SAI within 7 days after onset of symptoms and neurological outcome after 3 months	To assess the independent effect of SAI over the functional outcome at 3 months
Predictive immune score for ischemic progression	7 days after onset of symptoms	To establish a predictive score for ischemic progression based in a panel of immune biomarkers. Ischemic progression is defined as an increase of ≥4 points in the National Institutes of Health Stroke Scale(NIHSS) score in the absence of bleeding in the CT scan.
Predictive immune score for functional outcome over the entire mRS	90 +-15 days after onset of symptoms	To establish a predictive score for functional outcome based in a panel of immune biomarkers and using shift analysis of the entire mRS
Insular cortex involvement and infarct volume	SAI within 7 days and and on the neurological outcome after 3 months	To investigate the influence of insular cortex involvement and infarct volume on the occurrence of a SAI and on the neurological outcome after 3 months

Trial Locations

Locations (1)

Functional Unit of Cerebrovascular Diseases, Hospital Clínic of Barcelona; 🇪🇸 Barcelona, Spain