Levels of Inflammatory Markers in the Treatment of Stroke-An SPS3 Ancillary Study

Study Overview
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Brief Summary
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The goals of this trial are to determine the prognostic significance of an elevated level of inflammatory blood markers in people who have experienced small subcortical strokes and who are enrolled in the Secondary Prevention of Small Subcortical Strokes (SPS3) trial.

Detailed Description
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Inflammation is increasingly recognized as playing a central role in atherosclerosis and coronary artery disease. And, peripheral blood markers of inflammation have been associated with incident and recurrent cardiac events. The relationship of these risk markers-which have the potential to be modified-to prognosis after ischemic stroke is less clear. The Levels of Inflammatory Markers in the Treatment of Stroke (LIMITS) study will address questions about the role of inflammatory markers in secondary stroke prevention in a cost-effective manner using the well-established framework of the Secondary Prevention of Small Subcortical Strokes (SPS3) trial. The SPS3 trial is an ongoing Phase 3, multicenter secondary stroke prevention trial that focuses on preventing stroke recurrence in people with small vessel ischemic stroke, or lacunes. The overall purpose of the LIMITS study is to determine if serum levels of inflammatory markers-such as hsCRP, serum amyloid A (SAA), CD40 ligand (CD40L), and monocyte chemoattractant protein-1 (MCP-1)-predict recurrent stroke and other vascular events among people with a history of small artery ischemic stroke. The project will also determine if these markers predict which people will respond best to dual antiplatelet therapy with clopidogrel and aspirin. The specific aims of LIMITS are to determine if hsCRP, SAA, CD40L, and MCP-1 levels are independent risk factors for recurrent ischemic stroke, and for recurrent ischemic stroke, myocardial infarction, and death in participants in the SPS3 trial after adjusting for demographic and traditional stroke risk factors, and other treatments, using a prospective cohort of people with small subcortical strokes from the SPS3 trial. LIMITS also aims to compare the efficacy of dual versus single antiplatelet therapy among participant groups with and without elevated baseline inflammatory marker levels for the outcome of a.) recurrent stroke, and b.) recurrent ischemic stroke, myocardial infarction, or death.

Official Title
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Levels of Inflammatory Markers in the Treatment of Stroke

Conditions
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Hypertension, Stroke

Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Patient must be randomized within 6 months of qualifying small subcortical stroke (S3) or subcortical TIA One of the following lacunar syndromes: PMH; pure sensory stroke; sensorimotor stroke; ataxic hemiparesis; dysarthria; hemiballism; PMH with facial sparing, horizontal gaze palsy, contralateral III palsy, contralateral VI palsy; Ataxia with contralateral III palsy; pure dysarthria Absence of cortical dysfunction (aphasia, apraxia, agnosia) No ipsilateral cervical carotid stenosis (>= 50%) if S3 is hemispheric No major-risk cardioembolic sources requiring anti-coagulation MRI evidence of S3 that is >=2.0 cm in diameter if DWI/bright lesion on FLAIR/T2 or <=1.5cm hypointense lesion on FLAIR/T1, corresponding to the qualifying event (required for all brainstem events) OR multiple S3 in cerebral hemispheres of <=1.5cm hypointense lesions on FLAIR/T1 AND absence of cortical stroke and large subcortical stroke. Exclusion Criteria: Disabling stroke (Ranking Scale >= 4) Prior hemorrhagic stroke Age <30 years High risk of bleeding (recurrent GI or GU bleeding, active peptic ulcer disease, etc) Need for long-term use of anticoagulants or other antiplatelet agents. Prior cortical or retinal stroke / TIA Prior ipsilateral carotid endarterectomy if hemispheric S3 Impaired renal function: GFR<40 cc/min Intolerance/contraindication to aspirin or clopidogrel Adjusted Folstein MMSE <24 Medical contraindication to MRI Pregnancy or child-bearing potential without contraception Other specific causes of stroke (e.g. dissection, vasculitis, drug abuse)

Ages Eligible for Study
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Minimum Age: 30 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| SPS3 patient cohort<br>All SPS3 patients who participate in Baseline and 1-Year F/U blood draw | |

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Percentage of participants with recurrent stroke | Participants with recurrence of any stroke during follow-up, including ischemic (an acute localized ischemic lesion in the brain not attributable to central nervous system infection, tumor, demyelinating, or degenerative neurologic diseases due to an occlusive vascular disorder) and hemorrhagic (acute extravasation of blood into the parenchyma of the central nervous system or subarachnoid space). | Up to 5 years | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Percentage of participants developing major cognitive decline | Documentation of a major cognitive decline during follow-up. This is a clinical decline in cognitive function manifested by functional deterioration/behavioral changes that are not associated with a clinical stroke event. Criteria: Both A and B must be met: A) A drop in the Cognitive Abilities Screening Instrument (CASI) score of > 10 points since study entry and sustained on repeat testing in approximately one month B) Associated behavioral changes and/or function | Up to 5 years | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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hypertension, stroke, cerebrovascular accident