Homocysteine Study (HOST)

End Stage Renal Disease Clinical Trial

Official title:

CSP #453 - Homocysteinemia in Kidney and Endstage Renal Disease Study (HOST)

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT00032435
• Other study ID #: 453
• Status: Completed
• Phase: Phase 3
• First received: March 20, 2002
• Last updated: October 14, 2010
• Start date: May 2001
• Est. completion date: September 2006

Study information

• Verified date: October 2010
• Source: VA Office of Research and Development
• Contact: n/a
• Is FDA regulated: No
• Health authority: United States: Federal GovernmentUnited States: Food and Drug Administration
• Study type: Interventional

Clinical Trial 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.

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 information / eligibility

• Status: Completed
• Enrollment: 2003
• Est. completion date: September 2006
• Est. primary completion date: August 2006
• Accepts healthy volunteers: No
• Gender: Both
• Age group: 21 Years and older

Eligibility

Inclusion Criteria:

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.

Exclusion Criteria:

Study Design

Masking: Double-Blind

Related Conditions & MeSH terms

• End Stage Renal Disease
• Kidney Diseases
• Kidney Failure, Chronic
• Renal Failure

Intervention

Drug:
• PAL-40 Active

• PAL-40 Placebo

Locations

Country	Name	City	State
Puerto Rico	VA Medical Center, San Juan	San Juan
United States	VA Ann Arbor Healthcare System	Ann Arbor	Michigan
United States	VA Medical Center, Bay Pines	Bay Pines	Florida
United States	VA Medical Center, Birmingham	Birmingham	Alabama
United States	VA Medical Center, Jamaica Plain Campus	Boston	Massachusetts
United States	VA Medical Center, Bronx	Bronx	New York
United States	VA Western New York Healthcare System at Buffalo	Buffalo	New York
United States	Ralph H Johnson VA Medical Center, Charleston	Charleston	South Carolina
United States	VA Medical Center, Cleveland	Cleveland	Ohio
United States	VA North Texas Health Care System, Dallas	Dallas	Texas
United States	VA Medical Center, Dayton	Dayton	Ohio
United States	VA Eastern Colorado Health Care System, Denver	Denver	Colorado
United States	John D. Dingell VA Medical Center, Detroit	Detroit	Michigan
United States	North Florida/South Georgia Veterans Health System	Gainesville	Florida
United States	Edward Hines, Jr. VA Hospital	Hines	Illinois
United States	Michael E. DeBakey VA Medical Center (152)	Houston	Texas
United States	Richard Roudebush VA Medical Center, Indianapolis	Indianapolis	Indiana
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 Medical Center, Memphis	Memphis	Tennessee
United States	Health Economics Resource Center (HERC), Menlo Park	Menlo Park	California
United States	VA Medical Center, Miami	Miami	Florida
United States	Zablocki VA Medical Center, Milwaukee	Milwaukee	Wisconsin
United States	VA Medical Center, Minneapolis	Minneapolis	Minnesota
United States	Southeast Veterans Healthcare System, New Orleans	New Orleans	Louisiana
United States	New York Harbor HCS	New York	New York
United States	VA Medical Center, Northport	Northport	New York
United States	VA Palo Alto Health Care System	Palo Alto	California
United States	VA Pittsburgh Health Care System	Pittsburgh	Pennsylvania
United States	VA Medical Center, Portland	Portland	Oregon
United States	Hunter Holmes McGuire VA Medical Center	Richmond	Virginia
United States	VA San Diego Healthcare System, San Diego	San Diego	California
United States	VA Puget Sound Health Care System, Seattle	Seattle	Washington
United States	VA Medical Center, Syracuse	Syracuse	New York
United States	VA Medical Center, DC	Washington	District of Columbia
United States	VA Connecticut Health Care System (West Haven)	West Haven	Connecticut
United States	West Palm Beach VA Medical Center	West Palm Beach	Florida

Sponsors (3)

Lead Sponsor	Collaborator
VA Office of Research and Development	Abbott Diagnostics Division, Pan American Laboratories

Countries where clinical trial is conducted

United States,  Puerto Rico,