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

Stroke Clinical Trial

— LIMITS  

Official title:

Levels of Inflammatory Markers in the Treatment of Stroke

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT00579306
• Other study ID #: AAAB1202
• Secondary ID: R01NS050724
• Status: Completed
• Phase: N/A
• First received: December 20, 2007
• Last updated: July 20, 2017
• Start date: June 2005
• Est. completion date: July 2012

Study information

• Verified date: July 2017
• Source: Columbia University
• Contact: n/a
• Is FDA regulated: No
• Study type: Observational

Clinical Trial 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.

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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 1244
• Est. completion date: July 2012
• Est. primary completion date: April 2012
• Accepts healthy volunteers: No
• Gender: All
• Age group: 30 Years and older

Eligibility

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)

Related Conditions & MeSH terms

• Hypertension
• Stroke

Locations

Country	Name	City	State
Canada	Hospital Charles LeMoyne Centre de recherché	Greenfield Park	Quebec
Canada	Dalhousie University Center for Clinical Research	Halifax	Nova Scotia
Canada	McGill University Health Center	Montreal	Quebec
Chile	Pontificia Universidad Catolica de Chile	Santiago
Chile	Hospital Naval Almirante Nef	Viña del Mar
Ecuador	Hospital-Clinica Kennedy	Guayaquil
Mexico	Universidad Autonoma de Guadalajara	Guadalajara	JAL
Mexico	Instituto Nacional de Neurología y Neurocirugía	Mexico	Mexico City
Peru	Hospital Nacional Alberto Sabogal	Lima
Spain	Hospital Clinico Universitario de Santiago de Compostela	Barcelona
Spain	Hospital del Mar	Barcelona
Spain	Hospital del Sagrat Cor	Barcelona
Spain	Hospital Dr. Josep Trueta	Barcelona
Spain	Hospital Germans Trias i Pujol,	Barcelona
Spain	Hospital Universitario de Bellvitge, Spain	Barcelona
United States	Boston University Medical Center	Boston	Massachusetts
United States	Cooper University Hospital,	Camden	New Jersey
United States	Metro Health Medical Center	Cleveland	Ohio
United States	University Hospitals of Cleveland, Case Western Reserve University,Case Western Neurological Unit, 11100 Euclid Avenue, Lakeside 5508	Cleveland	Ohio
United States	University of Texas South Western Medical Center	Dallas	Texas
United States	Mercy Medical Center	Des Moines	Iowa
United States	Henry Ford Health System	Detroit	Michigan
United States	Wayne State University	Detroit	Michigan
United States	The Methodist Hospital	Houston	Texas
United States	University of California, San Diego Medical Center	La Jolla	California
United States	University of Kentucky	Lexington	Kentucky
United States	Marshfield Clinic Research Foundation	Marshfield	Wisconsin
United States	Melbourne Internal Medicine Associates	Melbourne	Florida
United States	University of Miami	Miami	Florida
United States	Medical College of Wisconsin	Milwaukee	Wisconsin
United States	Hennepin County Medical Center	Minneapolis	Minnesota
United States	University of South Alabama	Mobile	Alabama
United States	Columbia University Medical Center	New York	New York
United States	Oregon Health and Science University	Portland	Oregon
United States	Mayo Clinic Rochester	Rochester	Minnesota
United States	Rochester General Hospital	Rochester	New York
United States	University of Rochester Medical Center	Rochester	New York
United States	Sutter Neuroscience Institute	Sacramento	California
United States	St. John's Mercy Medical Center	Saint Louis	Missouri
United States	St. Louis University	Saint Louis	Missouri
United States	University of Texas Health Science Center at San Antonio	San Antonio	Texas
United States	Mayo Clinic Scottsdale	Scottsdale	Arizona
United States	University of Arizona Collage of Medicine	Tucson	Arizona
United States	Helen Hayes Hospital	West Haverstraw	New York
United States	Wake Forest University Medical Center	Winston-Salem	North Carolina

Sponsors (2)

Lead Sponsor	Collaborator
Columbia University	National Institute of Neurological Disorders and Stroke (NINDS)

Countries where clinical trial is conducted

United States,  Canada,  Chile,  Ecuador,  Mexico,  Peru,  Spain, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	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	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