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

Sponsor

RWTH Aachen University (Other)

Overall Status

Completed

CT.gov ID

NCT01407601

Collaborator

(none)

Enrollment

Locations

Arms

Duration (Months)

17.7

Patients Per Site

Patients Per Site Per Month

Study Details

Study Description

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).

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

Study Design

Study Type:

Interventional

Actual Enrollment :

53 participants

Allocation:

Randomized

Intervention Model:

Parallel Assignment

Masking:

Double (Participant, 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

Study Start Date :

Jan 1, 2008

Actual Primary Completion Date :

May 1, 2008

Actual Study Completion Date :

Jul 1, 2009

Arms and Interventions

Arm	Intervention/Treatment
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

Arm

Intervention/Treatment

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

Outcome Measures

Primary Outcome Measures

Reduction of plasma levels of noncarboxylated MGP [after 6 weeks of supplementation]
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 [after 6 weeks of supplementation]
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) [after 6 weeks of supplementation]
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 [after 6 weeks of supplementation]
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 [after 6 weeks of supplementation]
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.

Eligibility Criteria

Criteria

Ages Eligible for Study:

18 Years and Older

Sexes Eligible for Study:

All

Accepts Healthy Volunteers:

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

Locations

	Site	City	State	Country	Postal Code
1	KfH Dialysis Unit Aachen	Aachen	NRW	Germany	52074
2	University Hospital of the RWTH Aachen	Aachen	NRW	Germany	52074
3	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