Vitamin K2 Supplementation to Activate Matrix Gla Protein (MGP) as Endogenous Inhibitor of Vascular Calcification in Hemodialysis Patients - Full Text View

Purpose

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).

Condition	Intervention	Phase
CKD 5D, Hemodialysis	Dietary Supplement: daily supplementation of MK-7 over 6 weeks	Phase 3


Study Type:	Interventional
Study Design:	Allocation: Randomized Endpoint Classification: Efficacy Study Intervention Model: Parallel Assignment Masking: Double Blind (Subject, Investigator) Primary Purpose: Basic Science
Official Title:	Food Supplementation With Vitamin K2 to Activate MGP as an Endogenous Inhibitor of Vascular Calcification in Hemodialysis Patients

Resource links provided by NLM:

MedlinePlus related topics: Dialysis Minerals Vitamin K

Drug Information available for: Menadione

U.S. FDA Resources

Further study details as provided by RWTH Aachen University:

Primary Outcome Measures:

Reduction of plasma levels of noncarboxylated MGP [ Time Frame: after 6 weeks of supplementation ] [ Designated as safety issue: No ]
Noncarboxylated MGP levels [pmol/L] will be determined from plasma samples by a non-commercial ELISA. Plasma samples will be obtained each week of the six-week treatment period and compared to baseline values.
Reduction of plasma levels of noncarboxylated osteocalcin [ Time Frame: after 6 weeks of supplementation ] [ Designated as safety issue: No ]
Noncarboxylated osteocalcin levels [ng/ml] will be determined from plasma samples by a commercial ELISA. Plasma samples will be obtained each week of the six-week treatment period and compared to baseline values.
Reduction of plasma levels of inactive prothrombin (PIVKA-II) [ Time Frame: after 6 weeks of supplementation ] [ Designated as safety issue: No ]
PIVKA-II levels [ng/ml] will be determined from plasma samples by a commercial ELISA. Plasma levels at the end of the six-week treatment period will be compared to baseline levels.

Secondary Outcome Measures:

increase of plasma levels of carboxylated MGP [ Time Frame: after 6 weeks of supplementation ] [ Designated as safety issue: No ]
Carboxylated MGP levels [pmol/L] will be determined from plasma samples by a non-commercial ELISA. Plasma samples will be obtained each week of the six-week treatment period and compared to baseline values.
increase of plasma levels of carboxylated osteocalcin [ Time Frame: after 6 weeks of supplementation ] [ Designated as safety issue: No ]
Carboxylated MGP levels [ng/ml] will be determined from plasma samples by a commercial ELISA. Plasma samples will be obtained each week of the six-week treatment period and compared to baseline values.


Enrollment:	53
Study Start Date:	January 2008
Study Completion Date:	July 2009
Primary Completion Date:	May 2008 (Final data collection date for primary outcome measure)

Arms	Assigned Interventions
Experimental: 45 µg MK-7 45 µg MK-7 daily over 6 weeks	Dietary Supplement: daily supplementation of MK-7 over 6 weeks once daily intake of MK-7 prior to dialysis over 6 weeks
Experimental: 135 µg MK-7 135 µg MK-7 daily over 6 weeks	Dietary Supplement: daily supplementation of MK-7 over 6 weeks once daily intake of MK-7 prior to dialysis over 6 weeks
Experimental: 360 µg MK-7 360 µg MK-7 daily over 6 weeks	Dietary Supplement: daily supplementation of MK-7 over 6 weeks once daily intake of MK-7 prior to dialysis over 6 weeks

Eligibility


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

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

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: NCT01407601

Locations


Germany
KfH Dialysis Unit Aachen
Aachen, NRW, Germany, 52074
University Hospital of the RWTH Aachen
Aachen, NRW, Germany, 52074
Dialysis Unit Erkelenz
Erkelenz, NRW, Germany, 41812

Sponsors and Collaborators

RWTH Aachen University

Investigators


Principal Investigator:	Ralf Westenfeld, MD	University Clinic of the RWTH Aachen
Study Chair:	Georg Schlieper, MD	University Clinic of the RWTH Aachen
Study Chair:	Stefan Holzmann, MD	Dialysis Unit Erkelenz, Germany
Study Chair:	Stephan Heidenreich, MD	KfH Dialysis Centre Aachen, Schurzelter Strasse
Study Director:	Juergen Floege, MD	University Clinic of the RWTH Aachen
Study Chair:	Thilo Krueger, MD	University Hospital of the RWTH Aachen

More Information

Publications automatically indexed to this study by ClinicalTrials.gov Identifier (NCT Number):

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.


Responsible Party:	CTC Aachen, University Hospital of the RWTH Aachen
ClinicalTrials.gov Identifier:	NCT01407601 History of Changes
Other Study ID Numbers:	EK 111/07
Study First Received:	July 29, 2011
Last Updated:	August 1, 2011
Health Authority:	Ethics Commission at the Medical Faculty; University Hospital of the RWTH Aachen: Germany

Keywords provided by RWTH Aachen University:


vitamin K MK-7 Hemodialysis	vascular calcification Matrix Gla protein Osteocalcin

Additional relevant MeSH terms:


Calcinosis Vascular Calcification Calcium Metabolism Disorders Metabolic Diseases Vitamins Vitamin K Vitamin K 2 Vitamin MK 7	Micronutrients Growth Substances Physiological Effects of Drugs Antifibrinolytic Agents Fibrin Modulating Agents Molecular Mechanisms of Pharmacological Action Hemostatics Coagulants

ClinicalTrials.gov processed this record on September 23, 2016