Uremic Hyperhomocysteinemia -A Folate Trial for Possible Prevention of Cardiovascular Events - Full Text View

Purpose

Homocysteine recently gained access to the category of risk factor for the development of atherosclerotic cardiovascular disease in the general population. Chronic renal failure patients, even before being introduced to dialysis therapy have almost universal elevation of serum homocysteine; when on dialysis their mortality is above 50% related to cardiovascular disease that we might now speculate, with a contribution of potentially toxic levels of the aminoacid homocysteine.

Condition	Intervention	Phase
Uremia Chronic Renal Failure Hemodialysis Hyperhomocysteinemia Cardiovascular Disease	Drug: folate treatment	Phase 4


Study Type:	Interventional
Study Design:	Allocation: Randomized Endpoint Classification: Efficacy Study Intervention Model: Parallel Assignment Masking: Double-Blind Primary Purpose: Prevention
Official Title:	Randomized Clinical Trial of Folate Therapy/Placebo for Reduction of Homocysteine Serum Levels in Uremic Patients and Influence on Cardiovascular Mortality

Resource links provided by NLM:

Genetics Home Reference related topics: N-acetylglutamate synthase deficiency argininosuccinic aciduria citrullinemia ornithine translocase deficiency

MedlinePlus related topics: B Vitamins Dialysis Folic Acid

Drug Information available for: Folic acid Vitamin B Complex

Genetic and Rare Diseases Information Center resources: Inborn Amino Acid Metabolism Disorder

U.S. FDA Resources

Further study details as provided by Universidade Estadual de Londrina:

Primary Outcome Measures:

Lowering of Homocysteine blood levels in uremia.
Prevention of cardiovascular events

Secondary Outcome Measures:

Reduction of carotid intima-media thickness


Estimated Enrollment:	186
Study Start Date:	April 2003
Estimated Study Completion Date:	March 2005

Detailed Description:

We conducted a double blind , randomized, placebo controlled trial, for two years, enroling, simultaneously, 186 end-stage kidney disease patients of any cause, older than 18 years of age, stable on hemodialysis, assigned to receive either oral folic acid 10 mg three times a week on post dialysis sessions, under nurse supervision or an identical appearing placebo for the entire lenght of the study, from april 2003 to march 2005.

The two groups had similar baseline clinical and laboratory characteristics. There was no loss of follow-up. At admission, homocysteine serum levels were above 13,9 umol/L in 96.7% (median 25.0, range 9.3-104.0)with only five cases in the normal levels; homocysteine remained elevated at 6, 12 and 24 months on those receiving placebo; folate treatment significantly decreased total homocysteine levels to a median value of 10.5 umol/L (2.8 - 20.3)which remained at this level for the entire study time (P<0.001); every one was alive and tested at six months, sixty eight were either transplanted(15)or died (53) from cardiovascular disease(seventeen in the folic acid group and twenty one in the placebo (P>0.05)or other causes(15), after being included in the study. Intima-media wall thickness blinded measured at the common carotid artery decreased from 1.94+-0,59 mm to 1.67+-0.38 (P<0.001) with folate therapy and became thicker, from 1.86+-0.41 to 2.11+-0.48 mm in the placebo group.

In conclusion, folate treatment for two years was not effective on modifying cardiovascular death and non fatal cardiovascular events of this sample population with chronic uremia; however, the ultrasonographic evaluation of the common carotid arteries intima-media wall thickness at entry and twenty four months later unequivocally showed a significant thickness decrease with supervised folate intake.

Earlier prescription of folic acid might benefit patients with chronic renal failure,preventing cardiovascular deterioration

Eligibility


Ages Eligible for Study:	18 Years and older (Adult, Senior)
Genders Eligible for Study:	Both
Accepts Healthy Volunteers:	No

Criteria

Inclusion Criteria:

Patients stable on hemodialysis for 4 months or more
Eighteen years of age or older

Exclusion Criteria:

Potential kidney transplant from a living donor in the near future
Severe cardiovascular disease
Cancer and active inflammation

Contacts and Locations

Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT00317005

Locations


Brazil
Hospital Universitario regional do Note do Parana
Londrina, Parana, Brazil, 86020-320
University Hospital, State University of Londrina
Londrina, Parana, Brazil, 86020-320

Sponsors and Collaborators

Universidade Estadual de Londrina

Investigators


Study Director:	Altair J Mocelin, MD PHD	Nephrology, University Hospital, State University of Londrina

More Information

Publications:

Brenner RM, Wrone EM. The epidemic of cardiovascular disease in end-stage renal disease. Curr Opin Nephrol Hypertens. 1999 May;8(3):365-9. Review.


ClinicalTrials.gov Identifier:	NCT00317005 History of Changes
Other Study ID Numbers:	UEL/CPG/Nefro/Hcy
Study First Received:	April 18, 2006
Last Updated:	April 20, 2006
Health Authority:	Brazil: Ministry of Health

Keywords provided by Universidade Estadual de Londrina:


hemodialysis chronic uremia hyperhomocysteinemia folate

Additional relevant MeSH terms:


Cardiovascular Diseases Renal Insufficiency Kidney Failure, Chronic Hyperhomocysteinemia Uremia Kidney Diseases Urologic Diseases Renal Insufficiency, Chronic Amino Acid Metabolism, Inborn Errors Metabolism, Inborn Errors Genetic Diseases, Inborn Malabsorption Syndromes Metabolic Diseases	Vitamin B Deficiency Avitaminosis Deficiency Diseases Malnutrition Nutrition Disorders Folic Acid Vitamin B Complex Hematinics Vitamins Micronutrients Growth Substances Physiological Effects of Drugs

ClinicalTrials.gov processed this record on September 28, 2016