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

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ClinicalTrials.gov Identifier: NCT00579306
Recruitment Status : Completed
First Posted : December 24, 2007
Last Update Posted : July 24, 2017
National Institute of Neurological Disorders and Stroke (NINDS)
Information provided by (Responsible Party):
Mitchell S Elkind, Columbia University

Brief Summary:
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.

Condition or disease
Hypertension Stroke

Detailed Description:

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.

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Study Type : Observational
Actual Enrollment : 1244 participants
Observational Model: Cohort
Time Perspective: Prospective
Official Title: Levels of Inflammatory Markers in the Treatment of Stroke
Actual Study Start Date : June 2005
Actual Primary Completion Date : April 2012
Actual Study Completion Date : July 2012

Resource links provided by the National Library of Medicine

SPS3 patient cohort
All SPS3 patients who participate in Baseline and 1-Year F/U blood draw

Primary Outcome Measures :
  1. Percentage of participants with recurrent stroke [ Time Frame: Up to 5 years ]
    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).

Secondary Outcome Measures :
  1. Percentage of participants developing major cognitive decline [ Time Frame: Up to 5 years ]

    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

Biospecimen Retention:   Samples Without DNA
blood serum (ancillary study)

Information from the National Library of Medicine

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Ages Eligible for Study:   30 Years and older   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
Sampling Method:   Probability Sample
Study Population
Patients with a symptomatic small vessel stroke within prior 6 month and enrolled in SPS3

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)

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT00579306

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Sponsors and Collaborators
Columbia University
National Institute of Neurological Disorders and Stroke (NINDS)
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Principal Investigator: Mitchell S. Elkind, MD, MS, FAAN Columbia University
Principal Investigator: Oscar Benavente, MD UTHSC San Antonio (SPS3 Principal Investigator)
Principal Investigator: Robert Hart, MD UTHSC San Antonio (SPS3 Principal Investigator)
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Responsible Party: Mitchell S Elkind, Associate Professor of Neurology and Epidemiology (in the Sergievsy Center), Columbia University
ClinicalTrials.gov Identifier: NCT00579306    
Other Study ID Numbers: AAAB1202
R01NS050724 ( U.S. NIH Grant/Contract )
First Posted: December 24, 2007    Key Record Dates
Last Update Posted: July 24, 2017
Last Verified: July 2017
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: Undecided

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Studies a U.S. FDA-regulated Drug Product: No
Studies a U.S. FDA-regulated Device Product: No
Keywords provided by Mitchell S Elkind, Columbia University:
cerebrovascular accident
Additional relevant MeSH terms:
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Cerebrovascular Disorders
Brain Diseases
Central Nervous System Diseases
Nervous System Diseases
Vascular Diseases
Cardiovascular Diseases