This multicenter, double-blind, randomized, controlled clinical trial has been designed to determine whether the addition of a multivitamin with high dose folic acid, pyridoxine, and cyanocobalamin to best medical management and risk factor modification reduces recurrent cerebral infarction (primary endpoint) and myocardial infarction (secondary endpoint) in patients with a first nondisabling cerebral infarction (NDCI) who have elevated homocyst(e)ine levels. The fundamental eligibility criteria are the occurrence of a first-ever NDCI within 30 days prior to randomization and homoeyst(e)ine >10.5 nmo1/m1 at screening visit. Patients will be randomly assigned to receive a daily multivitamin containing, in addition to standard multivitamins, a high or low dose of folic acid, pyridoxine, and cyanocobalamin. Randomized patients will also receive a methionine loading test. All patients will receive best management for risk factor reduction. The study is designed to recruit 3600 patients (1800 in each group) over a 2-year-period for 80% power for detection of a 30% treatment effect. Follow-up continues until recurrent stroke, death, or a maximum of 2 years. Analysis will be in terms of original randomization (intent-to-treat analysis) using the log-rank test of difference in survival-without-endpoint curves. The incidence of second stroke in patients who have had a first stroke is between 7-10% per year. Myocardial infarction adds a major increment to morbidity and mortality. Because homocyst(e)ine may be a major contributor to the etiology of atherothrombotic disease and is an independent risk factor for these complications, its reduction by appropriate intervention with vitamin supplements could reduce the impact of recurrent stroke, myocardial infarction and vascular death. This inexpensive intervention has the potential for being added to other risk factor reduction customary therapy. It may substitute for more dangerous and complicated managements which include warfarin or more expensive therapies such as ticlopidine which are commonly advocated for secondary prevention of stroke, particularly in patients who are aspirin resistant. The long term effects and putative toxicity to vitamin supplementation will be delineate.

Agency
National Institute of Health (NIH)
Institute
National Institute of Neurological Disorders and Stroke (NINDS)
Type
Research Project (R01)
Project #
5R01NS034447-02
Application #
2460620
Study Section
Special Emphasis Panel (SRC (09))
Program Officer
Marler, John R
Project Start
1996-09-15
Project End
2001-07-31
Budget Start
1997-08-01
Budget End
1998-07-31
Support Year
2
Fiscal Year
1997
Total Cost
Indirect Cost
Name
Wake Forest University Health Sciences
Department
Neurology
Type
Schools of Medicine
DUNS #
041418799
City
Winston-Salem
State
NC
Country
United States
Zip Code
27106
Davis Armstrong, Nicole M; Chen, Wei-Min; Brewer, Michael S et al. (2018) Epigenome-Wide Analyses Identify Two Novel Associations With Recurrent Stroke in the Vitamin Intervention for Stroke Prevention Clinical Trial. Front Genet 9:358
Fernández-Cadenas, Israel; Mendióroz, Maite; Giralt, Dolors et al. (2017) GRECOS Project (Genotyping Recurrence Risk of Stroke): The Use of Genetics to Predict the Vascular Recurrence After Stroke. Stroke 48:1147-1153
Woo, Daniel; Debette, Stephanie; Anderson, Christopher (2017) 20th Workshop of the International Stroke Genetics Consortium, November 3-4, 2016, Milan, Italy: 2016.036 ISGC research priorities. Neurol Genet 3:S12-S18
Williams, Stephen R; Hsu, Fang-Chi; Keene, Keith L et al. (2016) Shared genetic susceptibility of vascular-related biomarkers with ischemic and recurrent stroke. Neurology 86:351-9
Marceau, Rachel; Lu, Wenbin; Holloway, Shannon et al. (2015) A Fast Multiple-Kernel Method With Applications to Detect Gene-Environment Interaction. Genet Epidemiol 39:456-68
Carty, Cara L; Keene, Keith L; Cheng, Yu-Ching et al. (2015) Meta-Analysis of Genome-Wide Association Studies Identifies Genetic Risk Factors for Stroke in African Americans. Stroke 46:2063-8
Huang, Jie; Huffman, Jennifer E; Yamakuchi, Munekazu et al. (2014) Genome-wide association study for circulating tissue plasminogen activator levels and functional follow-up implicates endothelial STXBP5 and STX2. Arterioscler Thromb Vasc Biol 34:1093-101
Yadav, Sunaina; Cotlarciuc, Ioana; Munroe, Patricia B et al. (2013) Genome-wide analysis of blood pressure variability and ischemic stroke. Stroke 44:2703-2709
Lee, Meng; Markovic, Daniela; Ovbiagele, Bruce (2013) Impact and interaction of low estimated GFR and B vitamin therapy on prognosis among ischemic stroke patients: the Vitamin Intervention for Stroke Prevention (VISP) trial. Am J Kidney Dis 62:52-7
Traylor, Matthew; Farrall, Martin; Holliday, Elizabeth G et al. (2012) Genetic risk factors for ischaemic stroke and its subtypes (the METASTROKE collaboration): a meta-analysis of genome-wide association studies. Lancet Neurol 11:951-62

Showing the most recent 10 out of 26 publications