End Stage Renal DiseasePhase 3NCT00032435
Homocysteine Study (HOST)
A Phase 3 study testing PAL-40 Active in people with End Stage Renal Disease and Renal Failure, run by US Department of Veterans Affairs at 37 sites in 2 countries.
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… Read more about this study
- Who is it for?
- Ages 21 years and older
- Conditions the study is for
- End Stage Renal Disease, Renal Failure
- What is being tested?
- PAL-40 Active
- Could I receive a placebo?
- Yes, some participants may receive a placebo
- How many people
- 2,003 participants
- Where
- 37 sitesin 2 countries
- Study dates
- May 2001to Sep 2006
- Phase
- Phase 3
- Are there results?
- None posted in the registry
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 21 years and older
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- 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.
Who cannot join
None listed.
Trial locations and contacts
37 sites in 2 countries.
37 sites in 2 countries
United States36 sites
VA Ann Arbor Healthcare System
Ann Arbor, Michigan, 48113
VA Medical Center, Bay Pines
Bay Pines, Florida, 33708
VA Medical Center, Birmingham
Birmingham, Alabama, 35233
VA Medical Center, Jamaica Plain Campus
Boston, Massachusetts, 02130
VA Western New York Healthcare System at Buffalo
Buffalo, New York, 14215
Ralph H Johnson VA Medical Center, Charleston
Charleston, South Carolina, 29401-5799
VA Medical Center, Cleveland
Cleveland, Ohio, 44106
VA North Texas Health Care System, Dallas
Dallas, Texas, 75216
VA Medical Center, Dayton
Dayton, Ohio, 45428
VA Eastern Colorado Health Care System, Denver
Denver, Colorado, 80220
John D. Dingell VA Medical Center, Detroit
Detroit, Michigan, 48201
North Florida/South Georgia Veterans Health System
Gainesville, Florida, 32608
Edward Hines, Jr. VA Hospital
Hines, Illinois, 60141-5000
Michael E. DeBakey VA Medical Center (152)
Houston, Texas, 77030
Richard Roudebush VA Medical Center, Indianapolis
Indianapolis, Indiana, 46202-2884
G.V. (Sonny) Montgomery VA Medical Center, Jackson
Jackson, Mississippi, 39216
VA Medical Center, Kansas City MO
Kansas City, Missouri, 64128
VA Medical Center, Memphis
Memphis, Tennessee, 38104
Health Economics Resource Center (HERC), Menlo Park
Menlo Park, California, 94025
VA Medical Center, Miami
Miami, Florida, 33125
Zablocki VA Medical Center, Milwaukee
Milwaukee, Wisconsin, 53295-1000
VA Medical Center, Minneapolis
Minneapolis, Minnesota, 55417
Southeast Veterans Healthcare System, New Orleans
New Orleans, Louisiana, 70112
New York Harbor HCS
New York, New York, 10010
VA Medical Center, Northport
Northport, New York, 11768
VA Palo Alto Health Care System
Palo Alto, California, 94304-1290
VA Pittsburgh Health Care System
Pittsburgh, Pennsylvania, 15240
VA Medical Center, Portland
Portland, Oregon, 97201
Hunter Holmes McGuire VA Medical Center
Richmond, Virginia, 23249
VA San Diego Healthcare System, San Diego
San Diego, California, 92161
VA Puget Sound Health Care System, Seattle
Seattle, Washington, 98108
VA Medical Center, Syracuse
Syracuse, New York, 13210
VA Medical Center, Bronx
The Bronx, New York, 10468
VA Medical Center, DC
Washington D.C., District of Columbia, 20422
VA Connecticut Health Care System (West Haven)
West Haven, Connecticut, 06516
West Palm Beach VA Medical Center
West Palm Beach, Florida, 33410
About this study
Official title: 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.
Read the 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.
- Conditions
- End Stage Renal Disease, Renal Failure
- Being tested
- PAL-40 Active, PAL-40 Placebo
- Keywords
- folate, pyridoxine, vitamin B6, cyanocobalamin, homoc
- Medical subject headings
- Kidney Failure, Chronic, Renal Insufficiency
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
PAL-40 ActiveDrug
PAL-40 PlaceboDrug
| Study group | Role | What they receive |
|---|---|---|
| 1 | Experimental | PAL-40 Active Receives: Drug: PAL-40 Active |
| 2 | Placebo comparator | PAL-40 Placebo Receives: Drug: PAL-40 Placebo |
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted22 Mar 2002 (estimated)
- Study startMay 2001
- Primary completionAug 2006
- Study completionSep 2006
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (3)Papers the sponsor has linked to this study.
- Other trials for End Stage Renal DiseaseStudies of the same condition, open and under way.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 3
- Masking
- Double blind
- Enrolment
- 2,003 participants (estimated)
Sponsor and investigators
- Lead sponsor
- US Department of Veterans Affairs
- Sponsor type
- US federal agency
- Collaborators
- Pan American Laboratories, Abbott Diagnostics Division
- Investigators
- Rex L. Jamison, Study chair, VA Palo Alto Health Care System
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT00032435
- Sponsor's protocol ID
- 453
- Status last verified
- Oct 2010
- First submitted
- 20 Mar 2002
- Last updated
- 15 Oct 2010
- Results posted
- No
- Data monitoring committee
- No
Publications
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.
PubMed 19628319Jamison 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.
PubMed 19272686Jamison 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.
PubMed 17848650
Study at a glance
From the registry record, last updated by the sponsor on 15 Oct 2010. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- CSP #453 - Homocysteinemia in Kidney and Endstage Renal Disease Study (HOST)
- ClinicalTrials.gov ID
- NCT00032435
- Acronym / sponsor ID
- 453
- Conditions
- End Stage Renal Disease, Renal Failure
- Keywords
- folate, pyridoxine, vitamin B6, cyanocobalamin, homoc
- Phase
- Phase 3
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 2,003 participants (estimated)
- Lead sponsor
- US Department of Veterans AffairsUS federal agency
- Collaborators
- Pan American Laboratories, Abbott Diagnostics Division
- Study start
- May 2001
- Primary completion
- Aug 2006 (actual)
- Study completion
- Sep 2006 (actual)
- First posted
- 22 Mar 2002 (estimated)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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.
Study design
- Masking
- Double blind
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| 1 | Experimental | Drug: PAL-40 ActivePAL-40 Active |
| 2 | Placebo comparator | Drug: PAL-40 PlaceboPAL-40 Placebo |
Who may qualify
- Ages
- 21 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (2 listed)
- 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.
Key exclusion criteria (0 listed)
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| PAL-40 Active | Drug | 1 |
| PAL-40 Placebo | Drug | 2 |
Primary outcome
Not reported in the source record.
Results and safety
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 15 Oct 2010.
- Derived from this study: PubMed 19628319Brady 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.
- Derived from this study: PubMed 19272686Jamison 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.
- Derived from this study: PubMed 17848650Jamison 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.
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Rex L. Jamison study chair
VA Palo Alto Health Care System
37 sites in 2 countries: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 3 study testing PAL-40 Active in people with End Stage Renal Disease and Renal Failure, run by US Department of Veterans Affairs at 37 sites in 2 countries.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 2 inclusion and 0 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: finished, as of the sponsor's last update on 15 Oct 2010. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 37 sites in United States, Puerto Rico. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. Some participants in this study may receive a placebo. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 3 studies compare the treatment with the current standard treatment or a placebo in a large group, to confirm how well it works and watch for side effects.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT00032435, which also lists 3 linked publications.
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 15 Oct 2010.