The Genomics and Randomized Trials Network (GARNET) Vitamin Intervention Stroke Prevention (VISP) Trial

The VISP trial (PI Jim Toole, M.D., Wake Forest University School of Medicine) was a multi-center, double-blind, randomized, controlled clinical trial that enrolled patients aged 35 or older with homocysteine (Hcy) levels above the 25th percentile at screening and a non-disabling cerebral infarction (NDCI) within 120 days of randomization (Toole, 2002, PMID: 12417369). The trial was designed to determine if daily intake of a multivitamin tablet with high dose folic acid, vitamin B6 and vitamin B12 reduced recurrent cerebral infarction (primary endpoint), and nonfatal myocardial infarction (MI) or mortality (secondary endpoints). Subjects were randomly assigned to receive daily doses of the high-dose formulation (n=1,827), containing 25mg pyridoxine (B6), 0.4mg cobalamin (B12), and 2.5mg folic acid; or the low-dose formulation (n=1,853), containing 200mcg pyridoxine, 6mcg cobalamin and 20mcg folic acid. Enrollment in VISP began in August 1997, and was completed in December 2001, with 3,680 participants enrolled. Within the trial, 2,164 participants from 46 clinic sites provided DNA and agreed for it to be shared for use in a genetic subset study of VISP. This study is part of Genomics and Randomized Trials Network (GARNET), funded by the National Human Genome Research Institute (NHGRI). The overarching goal is to identify novel genetic factors that contribute to stroke through large-scale genome-wide association studies of treatment response in randomized clinical trials. Genotyping was performed at the Johns Hopkins University Center for Inherited Disease Research (CIDR). Data cleaning and harmonization were performed at the GARNET Coordinating Center at the University of Washington. The data of the VISP trial have been released to dbGaP users in several segments: Version 1 (phs000343.v1.p1), consisted of n=4 phenotype datasets, and all raw, cleaned and imputed genotype data. Version 2 (phs000343.v2.p1) included n=14 additional phenotype datasets (plus pedigree, consent, and sample-mapping data), and increased the available data to a total of n=970 phenotype variables. Version 3 (phs000343.v3.p1) included all n=36 phenotype datasets (plus pedigree, consent, and sample-mapping data), and increased the available data to a total of n=1918 phenotype variables.Version 4 (phs000343.v4.p1), the current release, includes all previous phenotypic datasets, includes one new phenotypic dataset for the untargeted metabolomics data of 50 individuals, includes DNA methylation profiles for n=180 individuals, and sequencing data for n=179 individuals. ]]>
Barthel Stroke Questionnaire (BARA)Baseline Stroke Symptoms Form (BSSA)Coronary Endpoint Diagnosis Form (CEDE)Change in Follow-Up Status Form (CFSB)CT/MRI Form (CTIA)Death Certificate Form (DCTB)Death Endpoint Review Form (DERA)Dietary Supplement Form (DSFA)12-Month Dietary Intake Form (DTXA)ECG Form (ECGA)Eligibility Checklist Form (ELCE)Stroke Endpoint Review Full Committee Meeting Form (FCMA)Follow-Up to Drop-Out Form (FDOA)Follow-Up Dietary Supplement Form (FDSA)Follow-Up Dietary Intake Form (FDTA)Potential Stroke in Fatal Cases Lacking FSS or NIH Primary Endpoint Diagnosis Form (FEDB)Follow-Up Inventory Log (FILA)Follow-Up Rose Angina Questionnaire (FRQB)Follow-Up Stroke Symptoms Form (FSSB)Hospitalization ECG Form (HCGA)Hospitalization Form (HOSD)Informant Interview Form (IFIA)Medication Survey Form (MEDB)Medical Exam Follow-Up Contact (MFOC)Medical History and Exam Form (MHXA)Mortality for Lost to Follow-Up (MLFB)Mini-Mental Status Exam Form (MMSA)Neurological Exam Form (NEUA)NIH Stroke Scale Questionnaire (NIHB)Primary Endpoint Diagnosis Form (PEDE)Physician Questionnaire Form (PHQA)Revised Endpoint Diagnosis Form (REDE)Revised Potential Fatal Stroke Lacking FSS or NIH Primary Endpoint Diagnosis Form (RFDB)Rose Questionnaire for Angina Form (ROSA)Rankin Stroke Scale Form (RSSA)Subject Tracking Form (STFA)Transfer of Patients Form (TRNA)Vitamin Cessation Form (VCFA)Vitamin Distribution Log (VDLA)VISP Consent to Participate in a Research StudyVISIT and O_VISIT DescriptionVISP ProtocolVitamin Adherence Form (VITB)Venipuncture/Methionine Load Form (VMLA)Coroner/Medical Examiner Form (CORA)Dietary Intake Form (DTIA)VISP Documentation Part 1VISP Documentation Part 2VISP Documentation Part 3VISP Documentation Part 4Inclusion Criteria: Age at least 35 years on the date of randomization, Randomization within 120 days of stroke, Patient is geographically accessible for follow-up and adequate means of transportation between the patient's home and clinic facilities/personnel can be arranged, Patient's compliance with study multivitamin during run-in period is 75% or higher, Patient agrees to take study medication, Patient signs informed consent Exclusion Criteria: Stroke due to any form of intracranial hemorrhage, dissection of a cervico-cephalic artery, veno-occlusive disease, drug abuse, or vasculitis, CT or MRI of the brain showing lesion other than infarction as cause of syndrome, Modified Rankin score of 4 or 5 at the time of eligibility determination, Presence of specific potential sources of cardiogenic emboli: atrial fibrillation within 30 days of stroke; or history of prosthetic cardiac valve, intracardiac thrombus or neoplasm, or valvular vegetation Presence of major neurologic illness apart from stroke that would prevent proper evaluation of recurrent stroke, Presence of cancer, pulmonary disease, or other illness which, in the opinion of the study physician, would limit the life expectancy of the patient to less than two years, Severe congestive heart failure, Renal insufficiency requiring dialysis, Untreated pernicious anemia or untreated B12 deficiency, Uncontrolled hypertension defined as systolic blood pressure >185 mm or diastolic >105 mm on two readings separated by five minutes at time of eligibility determination, Conditions that prevent reliable participation in the study, such as refractory depression, severe cognitive impairment, alcoholism, or other substance abuse, Use of medications (within the last 30 days) that affect homocyst(e)ine: methotrexate, tamoxifen, L-DOPA, or phenytoin or bile acid sequestrants that can decrease folate levels, Woman of childbearing potential, defined as not having reached menopause (natural or surgical), Participation in another trial in which active intervention is being received, Patients on multivitamin supplements or single vitamins of B6 or folic acid will be excluded unless they are willing to take the study supplements in place of the one(s) they usually take Any surgical procedure requiring a general anesthesia or hospital stay of three or more days, any type of invasive cardiac instrumentation, or an endarterectomy, stent placement, thrombectomy, or any other endovascular treatment of an abnormal carotid artery performed within 30 days prior to randomization or scheduled to be performed within 30 days after randomization ]]>
Original VISP Study Timeline Pilot Test Recruitment Follow-up Analysis Months 1-12 (Sept 96 -Aug 97) X Months 13-18 (Sept 97 - Feb 98) X Months 19-24 (March 98 - Aug 98) X X Months 25-30 (Sept 98 -Feb 99) X X Months 31-36 (March 99 - Aug 99) X X Months 37-42 (Sept 99 - Feb 00) X X Months 43-50 (March 00 - Oct 00) X X Months 51-74 (Nov 00 - Oct 02) X Months 75-86 (Nov 02-Oct 03) X ]]>