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

Phase 3
Completed
Conditions
CKD 5D, Hemodialysis
Interventions
Dietary Supplement: daily supplementation of MK-7 over 6 weeks
Registration Number
NCT01407601
Lead Sponsor
RWTH Aachen University
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).

Detailed Description

Not available

Recruitment & Eligibility

Status
COMPLETED
Sex
All
Target Recruitment
53
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

Study & Design

Study Type
INTERVENTIONAL
Study Design
PARALLEL
Arm && Interventions
GroupInterventionDescription
45 µg MK-7daily supplementation of MK-7 over 6 weeks45 µg MK-7 daily over 6 weeks
135 µg MK-7daily supplementation of MK-7 over 6 weeks135 µg MK-7 daily over 6 weeks
360 µg MK-7daily supplementation of MK-7 over 6 weeks360 µg MK-7 daily over 6 weeks
Primary Outcome Measures
NameTimeMethod
Reduction of plasma levels of noncarboxylated MGPafter 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 osteocalcinafter 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
NameTimeMethod
increase of plasma levels of carboxylated MGPafter 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 osteocalcinafter 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.

Trial Locations

Locations (3)

University Hospital of the RWTH Aachen

🇩🇪

Aachen, NRW, Germany

KfH Dialysis Unit Aachen

🇩🇪

Aachen, NRW, Germany

Dialysis Unit Erkelenz

🇩🇪

Erkelenz, NRW, Germany

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