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

• ClinicalTrials.gov Identifier: NCT00317005
• Recruitment Status: Completed
• First Posted: April 21, 2006
• Last Update Posted: July 26, 2018
• Sponsor: Universidade Estadual de Londrina
• Information provided by: Universidade Estadual de Londrina

Study Description

Brief Summary:

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 or disease	Intervention/treatment	Phase
Uremia; Chronic Renal Failure; Hemodialysis; Hyperhomocysteinemia; Cardiovascular Disease	Drug: folate treatment	Phase 4

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

Study Design

• Study Type: Interventional (Clinical Trial)
• Enrollment: 186 participants
• Allocation: Randomized
• Intervention Model: Parallel Assignment
• Masking: Double
• 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
• Study Start Date: April 2003
• Study Completion Date: March 2005

Arms and Interventions

Outcome Measures

Primary Outcome Measures :

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

Secondary Outcome Measures :

1. Reduction of carotid intima-media thickness

Eligibility Criteria

• Ages Eligible for Study: 18 Years and older (Adult, Older Adult)
• Sexes Eligible for Study: All
• 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

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
• Other Study ID Numbers: UEL/CPG/Nefro/Hcy
• First Posted: April 21, 2006
• Last Update Posted: July 26, 2018
• Last Verified: May 2005

Keywords provided by Universidade Estadual de Londrina:

hemodialysis; chronic uremia; hyperhomocysteinemia; folate

Additional relevant MeSH terms:

Kidney Failure, Chronic; Uremia; Hyperhomocysteinemia; Cardiovascular Diseases; Renal Insufficiency; 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; Nutrients; Growth Substances; Physiological Effects of Drugs