Vascular calcification, vitamin K, phosphate binders and MGP|
|- candidate number||21131|
|- NTR Number||NTR5004|
|- ISRCTN||ISRCTN no longer applicable|
|- Date ISRCTN created|
|- date ISRCTN requested|
|- Date Registered NTR||9-dec-2014|
|- Secondary IDs||NL3681009413 |
|- Public Title||Vascular calcification, vitamin K, phosphate binders and MGP|
|- Scientific Title||Role of different phosphate binders on absorption of vitamin K, metabolism of matrix γ-carboxy-glutamaat (Gla) proteďne (MGP) |
|- ACRONYM||Vascular calcification, vitamin K, phosphate binders and MGP|
|- hypothesis||This research will have as aim to look at progression or decrease in vascular calcification in dialysis population with use different phosphate binders. There is a possibility that different binders bind vitamin K in a different way in intestinal tract and thereby cause different level of calcification. Better insight in mechanisms of vascular calcification under circumstance can lead to therapeutic options which inhibit calcification and benefit survival of dialysis patients. |
|- Healt Condition(s) or Problem(s) studied||Vascular calcification, Phosphate binders, Chronic renal failure, Vitamin K, MGP|
|- Inclusion criteria||Haemodialysis patients aged 18 years or above without the prospect of renal function recovery, planned renal transplantation, and life expectancy longer than six months.|
|- Exclusion criteria||1 Use of vitamin K antagonists|
2 Calcium under 2,1 mmol/l or above 2,6 mmol/l, after correction for albumin level
4 Baseline phosphate under 1,4 mmol/l
5 Allergy or intolerance for study medication
6 PTH <15 or >65 pmol/l
|- mec approval received||yes|
|- multicenter trial||no|
|- Type||2 or more arms, randomized|
|- planned startdate ||3-nov-2014|
|- planned closingdate||2-nov-2015|
|- Target number of participants||16|
|- Interventions||treatment with calciumcarbonate or lanthanum carbonate with supplemantation of vitamin K|
|- Primary outcome||Absolute difference between serum level of dp-ucMGP and PIVKA II at week 8 between phosphate binder groups (between group analysis).|
|- Secondary outcome||Absolute change from baseline to end of treatment period for lanthanumcarbonate group and calciumcarbonate group, respectively (longitudinal within group analysis). Association between change in dp-ucMGP and PIVKA II. Change in dp-ucMGP between week 16 and 20.|
|- Timepoints||start: start with one of the phosphate binders|
8 weeks: change of phosphate binder
16 weeks: start vitamin K2 supplemantation
20 weeks: end of trial
|- Trial web site|
|- status||open: patient inclusion|
|- CONTACT FOR PUBLIC QUERIES|| A. Neradova|
|- CONTACT for SCIENTIFIC QUERIES|| A. Neradova|
|- Sponsor/Initiator ||VU University Medical Center|
(Source(s) of Monetary or Material Support)
|Nederlandse nierstichting, Shire|
|- Publications||1 Arterial media calcification in end stage renal disease: impact on all cause and cardiovascular mortality. London GM, Guerin AP, Marchais S.J, et al. Nephrol Dial Transplant. 2003 Sept; 18(9): 1731-40.|
2 Braun J, Oldenhof M, Moshage W, et al.Electron beam computed tomography in the evaluation of cardiac calcification in chronic dialysis patients. Am J Kidney Dis. 1996 Mar; 27(3): 294-401.
3 Goodman W.G, Goldin J, Kuizon B.D, et al. Coronary-artery calcification in young adults with end-stage renal disease who are undergoing dialysis. N Engl J Med. 2000 May; 342 (20): 1478-83.
4 Chertow GM, Burke SK, Raggi P. Sevelamer attenuates the progression of coronary and aortic calcification in hemodialysis patients. Kidney Int. 2002 jul; 62 (1): 245-52.
5 McCullough P.A, Sandberg K.R, Dumler F, Yanez J.E. Determinants of coronary vascular calcification in patients with chronic kidney disease and end-stage renal disease: a systematic review. J Nephrol. 2004 Mar-Apr; 17(2): 205-15.
6 Moe SM, O’Neill KD, Reslerova M, et al. Natural history of vascular calcification in dialysis and transplant patients. Nephrol Dial Transplant. 2004; 19: 2387-93.
7 Luo G,Ducy P, McKee MD, et al. Spontaneous calcification of arteries and cartilage in mice lacking matrix GLA protein.Nature 1997; 386: 78-81.
8 Geleijnse JM, Vermeer C, Grobbee DE, et al. Dietary intake of menaquinone is associated with a reduced risk of coronary heart disease: the Rotterdam Study. J Nutr. 2004 Nov; 134(11): 3100-5.
9 Furie, B, Bouchard, B, Furie, BC.Vitamin K-dependent biosynthesis of gamma-carboxyglutamic acid. Blood 1999; 93:1798.
10 Davie, EW. Biochemical and molecular aspects of the coagulation cascade.ThrombHaemost 1995; 74:1.
11 Francucci CM, Ceccoli L, Rilli S, et al. Skeletal effects of oral anticoagulants. J Endocrinol Invest.2009; 32(4 Suppl): 27-31.
12 Schurgers LJ, Barreto DV, Barreto FC, et al. The circulating Inactive form of MGP is a surrogate marker for vascular calcification in chronic kidney disease: A preliminary report. J Am SocNephrol. 2010 Apr; 5(4): 568-75.
13 Geleijnse JM, Vermeer C, Grobbee DE, et al. Dietary intake of menaquinone is associated with a reduced risk of coronary heart disease: the Rotterdam Study. J Nutr. 2004 Nov; 134(11): 3100-5.
14 Krueger T, Westenfeld R, Ketteler M, Schurgers LJ, Floege J. Vitamin K deficiency in CKD patients, a modifiable risk factor for vascular calcification. Kidney International 2009; 76: 18–22.
15 Westenfeld R, Krueger T, Schlieper G, et al. Effect of vitamin K2 supplementation on functional vitamin K deficiency in hemodialysis patients: a randomized trial. Am J Kidney Dis.2012 Feb; 59(2):186-95.
16 Koos R, Mahnken AH, Muhlenbruch G, et al. Relation of oral anticoagulation to cardiac valvular and coronary calcium assessed by multislice spiral computed tomography. Am J Cardiol 2005; 96: 747-749.
17 Takagi K, Masuda K, Yamazaki M, et al. Metal and ion and vitamin adsorption profiles of phosphate binder ion-exchange resins. Clin. Nephrol. 2010 Jan; 73(1): 30-5.
18 Sevelamer Summary Product information.
19 Pierce D, Hossack S, Poole L, et al.The effect of sevelamer carbonate and lanthanum carbonate on the pharmacokinetics of oral calcitriol.Nephrol. Dial. Transplant. 2011 May; 26(5): 1615-21.
20 Block GA, Wheeler DC, Persky MS, et al. Effects of phosphate binders in moderate CKD. J. Am. Soc. Nephrol 2012 Aug; 23(8): 1407-15.
|- Brief summary||Vascular calcification (VC) is a problem in patients with chronic kidney disease especially in end stage kidney disease. VC is associated with increased mortality. In recent literature there is vascular calcification which progresses with use of phosphate binders. There are some small studies which have shown that phosphate binders can bind vitamin K as well. Vitamin K is necessary in the vessel wall to counteract VC. In this trial we are taking a better look at this interaction, because if phosphate binders bind vitamin K this can cause VC. |
|- Main changes (audit trail)|
|- RECORD||9-dec-2014 - 3-apr-2015|
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