Homocysteine Study (HOST)

October 14, 2010 updated by: US Department of Veterans Affairs

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

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.

Study Overview

Status

Completed

Conditions

Intervention / Treatment

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.

Study Type

Interventional

Enrollment (Anticipated)

2003

Phase

  • Phase 3

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Locations

  • Puerto Rico
      • San Juan, Puerto Rico, 00921
        • VA Medical Center, San Juan
  • United States
    • Alabama
      • Birmingham, Alabama, United States, 35233
        • VA Medical Center, Birmingham
    • California
      • Menlo Park, California, United States, 94025
        • Health Economics Resource Center (HERC), Menlo Park
      • Palo Alto, California, United States, 94304-1290
        • VA Palo Alto Health Care System
      • San Diego, California, United States, 92161
        • VA San Diego Healthcare System, San Diego
    • Colorado
      • Denver, Colorado, United States, 80220
        • VA Eastern Colorado Health Care System, Denver
    • Connecticut
      • West Haven, Connecticut, United States, 06516
        • VA Connecticut Health Care System (West Haven)
    • District of Columbia
      • Washington, District of Columbia, United States, 20422
        • VA Medical Center, DC
    • Florida
      • Bay Pines, Florida, United States, 33708
        • VA Medical Center, Bay Pines
      • Gainesville, Florida, United States, 32608
        • North Florida/South Georgia Veterans Health System
      • Miami, Florida, United States, 33125
        • VA Medical Center, Miami
      • West Palm Beach, Florida, United States, 33410
        • West Palm Beach VA Medical Center
    • Illinois
      • Hines, Illinois, United States, 60141-5000
        • Edward Hines, Jr. VA Hospital
    • Indiana
      • Indianapolis, Indiana, United States, 46202-2884
        • Richard Roudebush VA Medical Center, Indianapolis
    • Louisiana
      • New Orleans, Louisiana, United States, 70112
        • Southeast Veterans Healthcare System, New Orleans
    • Massachusetts
      • Boston, Massachusetts, United States, 02130
        • VA Medical Center, Jamaica Plain Campus
    • Michigan
      • Ann Arbor, Michigan, United States, 48113
        • VA Ann Arbor Healthcare System
      • Detroit, Michigan, United States, 48201
        • John D. Dingell VA Medical Center, Detroit
    • Minnesota
      • Minneapolis, Minnesota, United States, 55417
        • VA Medical Center, Minneapolis
    • Mississippi
      • Jackson, Mississippi, United States, 39216
        • G.V. (Sonny) Montgomery VA Medical Center, Jackson
    • Missouri
      • Kansas City, Missouri, United States, 64128
        • VA Medical Center, Kansas City MO
    • New York
      • Bronx, New York, United States, 10468
        • VA Medical Center, Bronx
      • Buffalo, New York, United States, 14215
        • VA Western New York Healthcare System at Buffalo
      • New York, New York, United States, 10010
        • New York Harbor HCS
      • Northport, New York, United States, 11768
        • VA Medical Center, Northport
      • Syracuse, New York, United States, 13210
        • VA Medical Center, Syracuse
    • Ohio
      • Cleveland, Ohio, United States, 44106
        • VA Medical Center, Cleveland
      • Dayton, Ohio, United States, 45428
        • VA Medical Center, Dayton
    • Oregon
      • Portland, Oregon, United States, 97201
        • VA Medical Center, Portland
    • Pennsylvania
      • Pittsburgh, Pennsylvania, United States, 15240
        • VA Pittsburgh Health Care System
    • South Carolina
      • Charleston, South Carolina, United States, 29401-5799
        • Ralph H Johnson VA Medical Center, Charleston
    • Tennessee
      • Memphis, Tennessee, United States, 38104
        • VA Medical Center, Memphis
    • Texas
      • Dallas, Texas, United States, 75216
        • VA North Texas Health Care System, Dallas
      • Houston, Texas, United States, 77030
        • Michael E. DeBakey VA Medical Center (152)
    • Virginia
      • Richmond, Virginia, United States, 23249
        • Hunter Holmes McGuire VA Medical Center
    • Washington
      • Seattle, Washington, United States, 98108
        • VA Puget Sound Health Care System, Seattle
    • Wisconsin
      • Milwaukee, Wisconsin, United States, 53295-1000
        • Zablocki VA Medical Center, Milwaukee

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

21 years and older (Adult, Older Adult)

Accepts Healthy Volunteers

No

Genders Eligible for Study

All

Description

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 Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Masking: Double

Arms and Interventions

Participant Group / Arm
Intervention / Treatment
Experimental: 1
PAL-40 Active
Drug: PAL-40 Active
Placebo Comparator: 2
PAL-40 Placebo
Drug: PAL-40 Placebo

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

US Department of Veterans Affairs

Collaborators

Abbott Diagnostics Division
Pan American Laboratories

Investigators

  • Study Chair: Rex L. Jamison, VA Palo Alto Health Care System

Publications and helpful links

The person responsible for entering information about the study voluntarily provides these publications. These may be about anything related to the study.

General Publications

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start

May 1, 2001

Primary Completion (Actual)

August 1, 2006

Study Completion (Actual)

September 1, 2006

Study Registration Dates

First Submitted

March 20, 2002

First Submitted That Met QC Criteria

March 21, 2002

First Posted (Estimate)

March 22, 2002

Study Record Updates

Last Update Posted (Estimate)

October 15, 2010

Last Update Submitted That Met QC Criteria

October 14, 2010

Last Verified

October 1, 2010

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

  • 453

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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