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

Study Overview
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Brief Summary
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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).

Official Title
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Food Supplementation With Vitamin K2 to Activate MGP as an Endogenous Inhibitor of Vascular Calcification in Hemodialysis Patients

Conditions
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CKD 5D, Hemodialysis

Intervention / Treatment
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* Dietary Supplement: daily supplementation of MK-7 over 6 weeks


Participation Criteria
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Eligibility Criteria
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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

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Basic Science
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Double


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: 45 µg MK-7<br>45 µg MK-7 daily over 6 weeks | Dietary Supplement: daily supplementation of MK-7 over 6 weeks<br>* once daily intake of MK-7 prior to dialysis over 6 weeks<br>|
| Experimental: 135 µg MK-7<br>135 µg MK-7 daily over 6 weeks | Dietary Supplement: daily supplementation of MK-7 over 6 weeks<br>* once daily intake of MK-7 prior to dialysis over 6 weeks<br>|
| Experimental: 360 µg MK-7<br>360 µg MK-7 daily over 6 weeks | Dietary Supplement: daily supplementation of MK-7 over 6 weeks<br>* once daily intake of MK-7 prior to dialysis over 6 weeks<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Reduction of plasma levels of noncarboxylated MGP | 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. | after 6 weeks of supplementation | 
| Reduction of plasma levels of noncarboxylated osteocalcin | 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. | after 6 weeks of supplementation | 
| Reduction of plasma levels of inactive prothrombin (PIVKA-II) | 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. | after 6 weeks of supplementation | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| increase of plasma levels of carboxylated MGP | 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. | after 6 weeks of supplementation | 
| increase of plasma levels of carboxylated osteocalcin | 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. | after 6 weeks of supplementation | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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vitamin K, MK-7, Hemodialysis, vascular calcification, Matrix Gla protein, Osteocalcin