Immunological Biomarkers in Patients With Acute Ischemic Stroke

Sponsor

Hospital Clinic of Barcelona (Other)

Overall Status

Completed

CT.gov ID

NCT01894529

Collaborator

Instituto de Salud Carlos III (Other)

132

Enrollment

Location

Duration (Months)

3.3

Patients Per Site Per Month

Study Details

Study Description

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.

Condition or Disease	Intervention/Treatment	Phase
Ischemic Stroke

Detailed Description

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+).

Study Design

Study Type:

Observational

Actual Enrollment :

132 participants

Observational Model:

Cohort

Time Perspective:

Prospective

Official Title:

Clinical Implications of a Panel of Immunological Biomarkers in Patients With Acute Ischemic Stroke

Study Start Date :

Jan 1, 2010

Actual Primary Completion Date :

May 1, 2013

Actual Study Completion Date :

May 1, 2013

Arms and Interventions

Arm	Intervention/Treatment
Ischemic stroke Patients with an ischemic stroke admitted within 6 hours of symptom onset, with a minimum severity in the NIHSS of 3 and treated with systemic or intraarterial thrombolysis
Healthy subjects Age-matched individuals free of acute neurological injury

Outcome Measures

Primary Outcome Measures

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

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
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
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
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
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

Eligibility Criteria

Criteria

Ages Eligible for Study:

18 Years and Older

Sexes Eligible for Study:

All

Accepts Healthy Volunteers:

Yes

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

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	Functional Unit of Cerebrovascular Diseases, Hospital Clínic of Barcelona	Barcelona		Spain	08036

Sponsors and Collaborators

Hospital Clinic of Barcelona
Instituto de Salud Carlos III

Investigators

Principal Investigator: Angel Chamorro, MD, PhD, Functional Unit of Cerebrovascular Diseases (Hospital Clínic of Barcelona), IDIBAPS and University of Barcelona Barcelona, Spain