Study Results
The study team has not published outcome measurements, participant flow, or safety data for this trial yet. Check back later for updates.
Basic Information
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COMPLETED
PHASE3
2003 participants
INTERVENTIONAL
2001-05-31
2006-09-30
Brief Summary
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Detailed Description
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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.
Conditions
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Study Design
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DOUBLE
Study Groups
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1
PAL-40 Active
PAL-40 Active
2
PAL-40 Placebo
PAL-40 Placebo
Interventions
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PAL-40 Active
PAL-40 Placebo
Eligibility Criteria
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Inclusion Criteria
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.
21 Years
ALL
No
Sponsors
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Pan American Laboratories
INDUSTRY
Abbott Diagnostics Division
INDUSTRY
US Department of Veterans Affairs
FED
Responsible Party
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Department of Veterans Affairs
Principal Investigators
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Rex L. Jamison
Role: STUDY_CHAIR
VA Palo Alto Health Care System
Locations
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VA Medical Center, Birmingham
Birmingham, Alabama, United States
Health Economics Resource Center (HERC), Menlo Park
Menlo Park, California, United States
VA Palo Alto Health Care System
Palo Alto, California, United States
VA San Diego Healthcare System, San Diego
San Diego, California, United States
VA Eastern Colorado Health Care System, Denver
Denver, Colorado, United States
VA Connecticut Health Care System (West Haven)
West Haven, Connecticut, United States
VA Medical Center, DC
Washington D.C., District of Columbia, United States
VA Medical Center, Bay Pines
Bay Pines, Florida, United States
North Florida/South Georgia Veterans Health System
Gainesville, Florida, United States
VA Medical Center, Miami
Miami, Florida, United States
West Palm Beach VA Medical Center
West Palm Beach, Florida, United States
Edward Hines, Jr. VA Hospital
Hines, Illinois, United States
Richard Roudebush VA Medical Center, Indianapolis
Indianapolis, Indiana, United States
Southeast Veterans Healthcare System, New Orleans
New Orleans, Louisiana, United States
VA Medical Center, Jamaica Plain Campus
Boston, Massachusetts, United States
VA Ann Arbor Healthcare System
Ann Arbor, Michigan, United States
John D. Dingell VA Medical Center, Detroit
Detroit, Michigan, United States
VA Medical Center, Minneapolis
Minneapolis, Minnesota, United States
G.V. (Sonny) Montgomery VA Medical Center, Jackson
Jackson, Mississippi, United States
VA Medical Center, Kansas City MO
Kansas City, Missouri, United States
VA Western New York Healthcare System at Buffalo
Buffalo, New York, United States
New York Harbor HCS
New York, New York, United States
VA Medical Center, Northport
Northport, New York, United States
VA Medical Center, Syracuse
Syracuse, New York, United States
VA Medical Center, Bronx
The Bronx, New York, United States
VA Medical Center, Cleveland
Cleveland, Ohio, United States
VA Medical Center, Dayton
Dayton, Ohio, United States
VA Medical Center, Portland
Portland, Oregon, United States
VA Pittsburgh Health Care System
Pittsburgh, Pennsylvania, 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
Michael E. DeBakey VA Medical Center (152)
Houston, Texas, United States
Hunter Holmes McGuire VA Medical Center
Richmond, Virginia, United States
VA Puget Sound Health Care System, Seattle
Seattle, Washington, United States
Zablocki VA Medical Center, Milwaukee
Milwaukee, Wisconsin, United States
VA Medical Center, San Juan
San Juan, , Puerto Rico
Countries
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References
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Brady CB, Gaziano JM, Cxypoliski RA, Guarino PD, Kaufman JS, Warren SR, Hartigan P, Goldfarb DS, Jamison RL. Homocysteine lowering and cognition in CKD: the Veterans Affairs homocysteine study. Am J Kidney Dis. 2009 Sep;54(3):440-9. doi: 10.1053/j.ajkd.2009.05.013. Epub 2009 Jul 23.
Jamison RL, Shih MC, Humphries DE, Guarino PD, Kaufman JS, Goldfarb DS, Warren SR, Gaziano JM, Lavori P; Veterans Affairs Site Investigators. Effect of the MTHFR C677T and A1298C polymorphisms on survival in patients with advanced CKD and ESRD: a prospective study. Am J Kidney Dis. 2009 May;53(5):779-89. doi: 10.1053/j.ajkd.2008.12.023. Epub 2009 Mar 9.
Jamison RL, Hartigan P, Kaufman JS, Goldfarb DS, Warren SR, Guarino PD, Gaziano JM; Veterans Affairs Site Investigators. Effect of homocysteine lowering on mortality and vascular disease in advanced chronic kidney disease and end-stage renal disease: a randomized controlled trial. JAMA. 2007 Sep 12;298(10):1163-70. doi: 10.1001/jama.298.10.1163.
Other Identifiers
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453
Identifier Type: -
Identifier Source: org_study_id