Homocysteine Study (HOST)
- Conditions
- End Stage Renal DiseaseRenal Failure
- Interventions
- Drug: PAL-40 ActiveDrug: PAL-40 Placebo
- Registration Number
- NCT00032435
- Lead Sponsor
- US Department of Veterans Affairs
- Brief Summary
The primary objective of this study is to test the hypothesis that administration of folate, pyridoxine (vitamin B6) and cyanocobalamin (vitamin B12) in high doses to patients with advanced chronic renal failure or end stage renal disease and abnormally high plasma homocysteine levels will lower the homocysteine levels and the death rate compared to patients who receive placebo. The secondary objective is to test the hypothesis that intake of the vitamins compared to placebo decreases the incidence of myocardial infarction, disabling stroke, and amputation of a lower extremity and, in hemodialysis patients, thrombosis of the vascular access.
- Detailed Description
Primary Hypothesis:
The primary objective of this proposal is to test the hypothesis that administration of folate, pyridoxine (vitamin B6) and cyanocobalamin (vitamin B12) in high doses to patients with advanced chronic renal failure or end-stage renal disease and abnormally high plasma homocysteine levels will lower the homocysteine levels and increase survival.
Secondary Hypotheses:
The secondary objectives are to test the hypotheses that intake of the vitamins decreases: 1) MI, 2) stroke, 3) amputation of lower extremity, 4) combination death, MI, stroke and amputation of lower extremity, 5) thrombosis of the vascular access in hemodialysis patients.
Primary Outcome: Death
Interventions: A treated group that receives a daily tablet containing 40mg of folic acid, 100mg of pyridoxine and 2mg of B12 versus a control group that receives a placebo.
Study Abstract:
The experimental design is a prospective, two-arm, randomized, double blind study, stratified for medical center and whether the patient has chronic renal failure or end-stage renal disease. In each arm 1003 patients will ingest daily a capsule containing either 40mg of folic acid, 100mg of pyridoxine and 2mg of vitamin B12, or placebo. We will use stratified randomization to ensure that the treatment is balanced within the end-stage renal disease patients and chronic renal failure patients.
This 6 year study will require an accrual phase of 2 years and a treatment phase lasting a minimum of 4 years. Patients will be screened by their plasma homocysteine concentration. They must have a level of at least 15 uM/L to be enrolled in the study. The study nurse will evaluate each patient at 3 months. Thereafter, patients will be contacted by phone, or mail if they prefer, at 3-month intervals by coordinators at a central location. Secondary endpoint events, hospitalization, onset of dialysis, and death or other reason for exit from the study will be recorded on standard forms. Plasma homocysteine levels will be obtained at 3 months in all patients.
Patients will be excluded if: age less than 21 years, expected life span less than 6 months, pregnancy, metastatic cancer, AIDS-related infection, end-stage liver disease, vitamin B12 deficiency, treatment with methotrexate, or anticonvulsants, unreliable or likely non-compliant, participation in other long-term trial, or unwilling or unable to give informed consent.
For a relative treatment effect of 17% (that is reducing the 3-year death rate from 28% to 23.2%) and 80% power, 2006 patients and 36 VA medical centers are required.
An abundance of published reports has shown a strong correlation between homocysteinemia and the incidence of cardiovascular death. Authors of these papers have unanimously recommended a study be undertaken to determine if folate, pyridoxine, and vitamin B12 can lower the incidence.
The study is to be conducted in patients with chronic renal failure and end-stage renal disease whose plasma homocysteine levels and incidence of cardiovascular death and disease are among the highest of all patient populations. By screening for patients with high plasma homocysteine concentrations and measuring the levels after 3 months, we will be able to determine if the hypothetical reduction in death and cardiovascular event rate is associated with a decrease in plasma homocysteine concentration.
Recruitment & Eligibility
- Status
- COMPLETED
- Sex
- All
- Target Recruitment
- 2003
Patients will be screened by their plasma homocysteine concentration. They must have a level of at least 15 mM/L to be enrolled in the study.
Patients will be excluded by any of the following criteria: age less than 21 years, expected life span less than 6 months, pregnancy, metastatic cancer, end-stage liver disease, treatment with methotrexate, other anti-folate medication or anticonvulsants, unreliable or likely noncompliant, participation in another long-term trial, or unwilling or unable to give informed consent.
Not provided
Study & Design
- Study Type
- INTERVENTIONAL
- Study Design
- Not specified
- Arm && Interventions
Group Intervention Description 1 PAL-40 Active PAL-40 Active 2 PAL-40 Placebo PAL-40 Placebo
- Primary Outcome Measures
Name Time Method
- Secondary Outcome Measures
Name Time Method
Trial Locations
- Locations (37)
VA Medical Center, Cleveland
🇺🇸Cleveland, Ohio, United States
New York Harbor HCS
🇺🇸New York, New York, United States
VA Medical Center, Northport
🇺🇸Northport, New York, United States
VA Western New York Healthcare System at Buffalo
🇺🇸Buffalo, New York, United States
Richard Roudebush VA Medical Center, Indianapolis
🇺🇸Indianapolis, Indiana, United States
John D. Dingell VA Medical Center, Detroit
🇺🇸Detroit, Michigan, United States
VA Medical Center, Minneapolis
🇺🇸Minneapolis, Minnesota, United States
VA Medical Center, Portland
🇺🇸Portland, Oregon, United States
Michael E. DeBakey VA Medical Center (152)
🇺🇸Houston, Texas, United States
VA Puget Sound Health Care System, Seattle
🇺🇸Seattle, Washington, United States
G.V. (Sonny) Montgomery VA Medical Center, Jackson
🇺🇸Jackson, Mississippi, United States
VA Eastern Colorado Health Care System, Denver
🇺🇸Denver, Colorado, United States
Zablocki VA Medical Center, Milwaukee
🇺🇸Milwaukee, Wisconsin, United States
VA Medical Center, Bronx
🇺🇸Bronx, New York, United States
West Palm Beach VA Medical Center
🇺🇸West Palm Beach, Florida, United States
VA Medical Center, DC
🇺🇸Washington, District of Columbia, United States
VA Medical Center, Bay Pines
🇺🇸Bay Pines, Florida, United States
VA Medical Center, Jamaica Plain Campus
🇺🇸Boston, Massachusetts, United States
VA Medical Center, Syracuse
🇺🇸Syracuse, New York, United States
VA Medical Center, Kansas City MO
🇺🇸Kansas City, Missouri, United States
VA Medical Center, Dayton
🇺🇸Dayton, Ohio, United States
VA Pittsburgh Health Care System
🇺🇸Pittsburgh, Pennsylvania, United States
Hunter Holmes McGuire VA Medical Center
🇺🇸Richmond, Virginia, United States
Ralph H Johnson VA Medical Center, Charleston
🇺🇸Charleston, South Carolina, United States
VA Medical Center, Memphis
🇺🇸Memphis, Tennessee, United States
VA North Texas Health Care System, Dallas
🇺🇸Dallas, Texas, United States
VA Medical Center, San Juan
🇵🇷San Juan, Puerto Rico
VA Medical Center, Birmingham
🇺🇸Birmingham, Alabama, United States
VA Medical Center, Miami
🇺🇸Miami, Florida, United States
North Florida/South Georgia Veterans Health System
🇺🇸Gainesville, Florida, United States
Southeast Veterans Healthcare System, New Orleans
🇺🇸New Orleans, Louisiana, United States
VA Palo Alto Health Care System
🇺🇸Palo Alto, California, United States
Health Economics Resource Center (HERC), Menlo Park
🇺🇸Menlo Park, California, United States
VA Ann Arbor Healthcare System
🇺🇸Ann Arbor, Michigan, United States
Edward Hines, Jr. VA Hospital
🇺🇸Hines, Illinois, United States
VA Connecticut Health Care System (West Haven)
🇺🇸West Haven, Connecticut, United States
VA San Diego Healthcare System, San Diego
🇺🇸San Diego, California, United States