5-methyltetrahydrofolate Survival and Inflammation in ESRD Patients

NCT00626223 | Completed

• 2 other identifiers: FCRB 2007/0234ndtso 00025/2007
• Study Type: interventional
• Target: 341
• Locations: 1 country
• Sites: 1

Brief Summary

A randomized prospective study was done to determine whether i.v. 5-methyltetrahydrofolate vs oral folate improved survival in ESRD patients. Homocysteine, CRP, Lp(a), albumin, folates, vitamin B6 and B12 were checked. The 5-MTHF treated group was associated with lowered C reactive protein and higher survival than the folate treated group.

Conditions

Mortality; Hyperhomocysteinemia; Inflammation

Keywords

ESRD patients; C-reactive protein; homocysteine; 5-MTHF; survival; Hemodialysis patients

Outcome Measures

Primary Outcomes (1)

• survival

  55 months

Secondary Outcomes (5)

• Risk factors for cardiovascular disease in ESRD patients

  55 months

• Homocysteine levels after 6, 12, 24 and 55 months

  55 months

• CRP levels after 6, 12, 24 and 55 months

  55 months

• Gene polymorphisms analysis on C677T and A1298C loci and differences in polymorphisms distribution in both groups

  basal

• Differences at baseline between the groups concerning age, dialysis age, CRP, albumin, haemoglobin, Lp(a), homocysteine, folate, B6 and B12 baseline levels

  basal

Study Arms (2)

A

EXPERIMENTAL

patients treated with intravenous 5-MTHF (Prefolic®, Knoll, Milan, Italy) 50 mg at the end of each hemodialysis session; The group will receive supplementation with vitamin B6 300 mg (Benadon®, Roche, Milan, Italy) and vitamin B12 1000 mcg (Dobetin®, A.C.R.A.F, Rome, Italy) administered by intravenous injection at the end of the hemodialysis session three times per week

Drug: 5-MTHF (5-methyltetrahydrofolate)

B

ACTIVE COMPARATOR

treated with 5 mg per day of oral folic acid (Folina® Schwarz Pharma, Milan, Italy). The group will receive supplementation with vitamin B6 300 mg (Benadon®, Roche, Milan, Italy) and vitamin B12 1000 mcg (Dobetin®, A.C.R.A.F, Rome, Italy) administered by intravenous injection at the end of the hemodialysis session three times per week

Drug: folic acid

Interventions

5-MTHF (5-methyltetrahydrofolate) DRUG

50 mg intravenous at the end of each hemodialysis session

A

folic acid DRUG

5 mg per day of oral folic acid

B

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Hemodialysis patients with age \> 18 years on regular bicarbonate hemodialysis or hemodiafiltration treatment three times a week
• Clinical stability at least three months before the study started
• Cardiovascular disease assessment as presence/absence of hypertension, ischemic cardiac disease, cerebral and peripheral vascular disease, diabetes.
• We will investigate coronary artery disease by determination of at least one of the following parameters:
• previous documentation of acute myocardial infarction (laboratory or ECG modifications);
• symptomatic CVD events in the clinical history confirmed by a positive treadmill test;
• coronary artery stenosis more than 50% in one of the three major coronary vessels documented by an angiographic study. All patients with coronary artery disease will be examined by a treadmill test (thallium scan) or coronary angiographic exam before entering the study.
• We will investigate cerebrovascular disease by one of the following criteria:
• a previous ictus (ongoing clinical evidence of neurological deficit in the three months before the study beginning, confirmed by a TC scan, a nuclear magnetic resonance or a physician's record of clinical history);
• carotid vessels stenosis more than 50% documented by a Doppler exam.
• Peripheral vascular disease will be assessed by the evidence of claudication intermittence, previous vascular surgical procedure (including amputation for ischemic limb or by angiographic/Doppler documentation of atherosclerotic plaques in abdominal, iliac and femoral vessels). The vascular surgical procedure will be carried out at least three months before the study started.

You may not qualify if:

• Diagnosis of one of the following clinical conditions in the last three months:
• acute infection
• vascular access thrombosis
• ictus cerebri
• myocardial infarction
• hemorrhage
• recent relevant surgery
• Malignancy
• Participation in other clinical trials

Sponsors & Collaborators

• IRCCS Azienda Ospedaliero-Universitaria di Bologna: lead
• University of Bologna: collaborator

Study Sites (1)

Nephrology Dialysis and Renal Transplantation Unit, S.Orsola University Hospital

Bologna, 40138, Italy

Location

Related Publications (16)

• Cheung AK, Sarnak MJ, Yan G, Berkoben M, Heyka R, Kaufman A, Lewis J, Rocco M, Toto R, Windus D, Ornt D, Levey AS; HEMO Study Group. Cardiac diseases in maintenance hemodialysis patients: results of the HEMO Study. Kidney Int. 2004 Jun;65(6):2380-9. doi: 10.1111/j.1523-1755.2004.00657.x.

  PMID: 15149351 BACKGROUND

• Nygard O, Vollset SE, Refsum H, Stensvold I, Tverdal A, Nordrehaug JE, Ueland M, Kvale G. Total plasma homocysteine and cardiovascular risk profile. The Hordaland Homocysteine Study. JAMA. 1995 Nov 15;274(19):1526-33. doi: 10.1001/jama.1995.03530190040032.

  PMID: 7474221 BACKGROUND

• Buccianti G, Baragetti I, Bamonti F, Furiani S, Dorighet V, Patrosso C. Plasma homocysteine levels and cardiovascular mortality in patients with end-stage renal disease. J Nephrol. 2004 May-Jun;17(3):405-10.

  PMID: 15365961 BACKGROUND

• Mallamaci F, Bonanno G, Seminara G, Rapisarda F, Fatuzzo P, Candela V, Scudo P, Spoto B, Testa A, Tripepi G, Tech S, Zoccali C. Hyperhomocysteinemia and arteriovenous fistula thrombosis in hemodialysis patients. Am J Kidney Dis. 2005 Apr;45(4):702-7. doi: 10.1053/j.ajkd.2005.01.004.

  PMID: 15806473 BACKGROUND

• Perna AF, De Santo NG, Ingrosso D. Adverse effects of hyperhomocysteinemia and their management by folic acid. Miner Electrolyte Metab. 1997;23(3-6):174-8.

  PMID: 9387111 BACKGROUND

• Kalantar-Zadeh K, Block G, Humphreys MH, McAllister CJ, Kopple JD. A low, rather than a high, total plasma homocysteine is an indicator of poor outcome in hemodialysis patients. J Am Soc Nephrol. 2004 Feb;15(2):442-53. doi: 10.1097/01.asn.0000107564.60018.51.

  PMID: 14747392 BACKGROUND

• Nair AP, Nemirovsky D, Kim M, Geer EB, Farkouh ME, Winston J, Halperin JL, Robbins MJ. Elevated homocysteine levels in patients with end-stage renal disease. Mt Sinai J Med. 2005 Nov;72(6):365-73.

  PMID: 16358160 BACKGROUND

• Bayes B, Pastor MC, Bonal J, Junca J, Hernandez JM, Riutort N, Foraster A, Romero R. Homocysteine, C-reactive protein, lipid peroxidation and mortality in haemodialysis patients. Nephrol Dial Transplant. 2003 Jan;18(1):106-12. doi: 10.1093/ndt/18.1.106.

  PMID: 12480967 BACKGROUND

• Bowden RG, Wyatt FB, Wilson R, Wilborn C, Gentile M. Homocysteine and vascular access thrombosis in a cohort of end-stage renal disease patients. Ren Fail. 2004 Nov;26(6):709-14. doi: 10.1081/jdi-200037117.

  PMID: 15600264 BACKGROUND

• Chen TC, Wang IK, Lee CH, Chang HW, Chiou TT, Lee CT, Fang JT, Wu MS, Hsu KT, Yang CC, Wang PH, Chuang FR. Hyperhomocysteinaemia and vascular access thrombosis among chronic hemodialysis patients in Taiwan: a retrospective study. Int J Clin Pract. 2006 Dec;60(12):1596-9. doi: 10.1111/j.1742-1241.2006.00848.x. Epub 2006 May 16.

  PMID: 16704682 BACKGROUND

• Chuang FR, Fang JT, Chen JB, Lin CL, Chen HY, Lee CN, Wang PH, Lee CH. Hyperhomocystinemia and the prevalence of symptomatic atherosclerotic vascular disease in Taiwanese chronic hemodialysis patients: a retrospective study. Ren Fail. 2003 Sep;25(5):765-74. doi: 10.1081/jdi-120024292.

  PMID: 14575285 BACKGROUND

• Dennis VW, Robinson K. Homocysteinemia and vascular disease in end-stage renal disease. Kidney Int Suppl. 1996 Dec;57:S11-7.

  PMID: 8941916 BACKGROUND

• Suliman ME, Stenvinkel P, Heimburger O, Barany P, Lindholm B, Bergstrom J. Plasma sulfur amino acids in relation to cardiovascular disease, nutritional status, and diabetes mellitus in patients with chronic renal failure at start of dialysis therapy. Am J Kidney Dis. 2002 Sep;40(3):480-8. doi: 10.1053/ajkd.2002.34887.

  PMID: 12200798 BACKGROUND

• Bonaa KH, Njolstad I, Ueland PM, Schirmer H, Tverdal A, Steigen T, Wang H, Nordrehaug JE, Arnesen E, Rasmussen K; NORVIT Trial Investigators. Homocysteine lowering and cardiovascular events after acute myocardial infarction. N Engl J Med. 2006 Apr 13;354(15):1578-88. doi: 10.1056/NEJMoa055227. Epub 2006 Mar 12.

  PMID: 16531614 BACKGROUND

• Lonn E, Yusuf S, Arnold MJ, Sheridan P, Pogue J, Micks M, McQueen MJ, Probstfield J, Fodor G, Held C, Genest J Jr; Heart Outcomes Prevention Evaluation (HOPE) 2 Investigators. Homocysteine lowering with folic acid and B vitamins in vascular disease. N Engl J Med. 2006 Apr 13;354(15):1567-77. doi: 10.1056/NEJMoa060900. Epub 2006 Mar 12.

  PMID: 16531613 BACKGROUND

• Touam M, Zingraff J, Jungers P, Chadefaux-Vekemans B, Drueke T, Massy ZA. Effective correction of hyperhomocysteinemia in hemodialysis patients by intravenous folinic acid and pyridoxine therapy. Kidney Int. 1999 Dec;56(6):2292-6. doi: 10.1046/j.1523-1755.1999.00792.x.

  PMID: 10594808 BACKGROUND

MeSH Terms

Conditions

Hyperhomocysteinemia; Inflammation

Interventions

5-methyltetrahydrofolate; Folic Acid

Condition Hierarchy (Ancestors)

Amino Acid Metabolism, Inborn Errors; Metabolism, Inborn Errors; Genetic Diseases, Inborn; Congenital, Hereditary, and Neonatal Diseases and Abnormalities; Malabsorption Syndromes; Metabolic Diseases; Nutritional and Metabolic Diseases; Vitamin B Deficiency; Avitaminosis; Deficiency Diseases; Malnutrition; Nutrition Disorders; Pathologic Processes; Pathological Conditions, Signs and Symptoms

Intervention Hierarchy (Ancestors)

Pterins; Pteridines; Heterocyclic Compounds, 2-Ring; Heterocyclic Compounds, Fused-Ring; Heterocyclic Compounds

Study Officials

• Sergio Stefoni, Professor

  Nephrology Dialysis and Renal Trasnplantation Unit S.Orsola University Hospital Bologna Italy

  STUDY CHAIR

Study Design

• Study Type: interventional
• Phase: not applicable
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER

Study Record Dates

• First Submitted: February 4, 2008
• First Posted: February 29, 2008
• Study Start: January 1, 1998
• Primary Completion: July 1, 2001
• Study Completion: July 1, 2007
• Last Updated: March 18, 2021

Record last verified: 2021-03

Locations

IT (1)