Clinical trial NCT01407601: Vitamin K2 Supplementation to Activate Matrix Gla Protein (MGP) as Endogenous Inhibitor of Vascular Calcification in Hemodialysis Patients
Official title: Food Supplementation With Vitamin K2 to Activate MGP as an Endogenous Inhibitor of Vascular Calcification in Hemodialysis Patients
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE3
Conditions: CKD 5D, Hemodialysis
Keywords: vitamin K
MK-7
Hemodialysis
vascular calcification
Matrix Gla protein
Osteocalcin
Lead sponsor: RWTH Aachen University
Sponsor class: OTHER
First posted: 2011-08-02
Enrollment: 53
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: BASIC_SCIENCE

Brief summary: Vascular calcification (VC) is a predictor of cardiovascular morbidity and mortality. Hemodialysis (HD) patients suffer from severe vascular calcifications. Matrix Gla protein (MGP) is a central calcification inhibitor of the arterial wall and its activity depends on vitamin K-dependent γ-glutamate carboxylation. Noncarboxylated MGP, formed as a result of vitamin K deficiency, is associated with cardiovascular disease. Recent studies pointed towards poor vitamin K status in HD patients. We therefore aim to investigate whether daily vitamin K2 (MK-7) supplementation improves the bioactivity of vitamin K-dependent proteins in HD patients as assessed by circulating dephospho-noncarboxylated MGP (dp-ucMGP), noncarboxylated osteocalcin (ucOC) and noncarboxylated prothrombin (ucFII; PIVKA-II).


Eligibility criteria: Inclusion Criteria:

* \> 18 years of age
* minimum of 3 months of hemodialysis
* written consent

Exclusion Criteria:

* chronic or acute bowel disease
* soy bean allergy
* active Vitamin K Supplementation
* oral anticoagulation with vitamin K Antagonists (coumarins)
* systemic therapy using steroids
* positive history for thrombosis or embolism
* pregnancy

Primary outcomes:
measure: Reduction of plasma levels of noncarboxylated MGP
timeFrame: after 6 weeks of supplementation
measure: Reduction of plasma levels of noncarboxylated osteocalcin
timeFrame: after 6 weeks of supplementation
measure: Reduction of plasma levels of inactive prothrombin (PIVKA-II)
timeFrame: after 6 weeks of supplementation
Secondary outcomes:
measure: increase of plasma levels of carboxylated MGP
timeFrame: after 6 weeks of supplementation
measure: increase of plasma levels of carboxylated osteocalcin
timeFrame: after 6 weeks of supplementation
Other outcomes:
Locations:
city: Aachen
country: Germany
facility: KfH Dialysis Unit Aachen
state: NRW
city: Aachen
country: Germany
facility: University Hospital of the RWTH Aachen
state: NRW
city: Erkelenz
country: Germany
facility: Dialysis Unit Erkelenz
state: NRW
Study officials:
affiliation: University Clinic of the RWTH Aachen
name: Ralf Westenfeld, MD
role: PRINCIPAL_INVESTIGATOR
affiliation: University Clinic of the RWTH Aachen
name: Georg Schlieper, MD
role: STUDY_CHAIR
affiliation: Dialysis Unit Erkelenz, Germany
name: Stefan Holzmann, MD
role: STUDY_CHAIR
affiliation: KfH Dialysis Centre Aachen, Schurzelter Strasse
name: Stephan Heidenreich, MD
role: STUDY_CHAIR
affiliation: University Clinic of the RWTH Aachen
name: Juergen Floege, MD
role: STUDY_DIRECTOR
affiliation: University Hospital of the RWTH Aachen
name: Thilo Krueger, MD
role: STUDY_CHAIR
References:
citation: Westenfeld R, Krueger T, Schlieper G, Cranenburg EC, Magdeleyns EJ, Heidenreich S, Holzmann S, Vermeer C, Jahnen-Dechent W, Ketteler M, Floege J, Schurgers LJ. 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. doi: 10.1053/j.ajkd.2011.10.041. Epub 2011 Dec 9.