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

This study has been completed.
Sponsor:
Information provided by:
RWTH Aachen University
ClinicalTrials.gov Identifier:
NCT01407601
First received: July 29, 2011
Last updated: August 1, 2011
Last verified: August 2011
  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:


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

No publications provided by RWTH Aachen University

Additional publications automatically indexed to this study by ClinicalTrials.gov Identifier (NCT Number):
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
Vitamin K
Vitamin K 2
Vitamins
Antifibrinolytic Agents
Fibrin Modulating Agents
Molecular Mechanisms of Pharmacological Action
Pharmacologic Actions
Hemostatics
Coagulants
Hematologic Agents
Therapeutic Uses
Micronutrients
Growth Substances
Physiological Effects of Drugs

ClinicalTrials.gov processed this record on August 28, 2014