The Effects of Vitamin K2 Supplementation on the Progression of Coronary Artery Calcification

Study Overview
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Brief Summary
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Both Coronary Artery Calcification (CAC)and its annual progression are a strong predictors of cardiovascular events. The development of arterial calcification results from imbalance between calcification promoting and inhibiting factors. An important inhibitor of calcification is Matrix Gla Protein (MGP): a protein present in the vascular wall where it is synthesized by Vascular Smooth Muscle Cells (VSMC). MGP requires Vitamin K-mediated carboxylation to function properly. Deficiency of Vitamin K has been demonstrated to cause arterial calcification and a diet containing large amounts of Vitamin K2 was associated with lower CAC and cardiovascular risk. In animal studies, active supplementation of Vitamin K2 caused regression of existing arterial calcification. Therefore, the aim of this randomized, double-blind, placebo-controlled clinical trial is to investigate whether daily supplementation of Vitamin K2 (Menaquinone-7) to patients with established CAC will lead to a decreased progression-rate of CAC after 24 months of follow-up in comparison to placebo.

Official Title
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The Effects of Vitamin K2 Supplementation on the Progression of Coronary Artery Calcification

Conditions
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Coronary Artery Disease

Intervention / Treatment
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* Dietary Supplement: Menaquinone-7 (Vitamin K2)
* Other: Placebo capsules


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Age 18 years or older Baseline Coronary Computed Tomographic Angiography (CCTA) of sufficient quality Baseline Agatston calciumscore 100 - 400 Exclusion Criteria: Baseline-scan of insufficient quality Heart rate greater than 70 beats per minute during first scan.(despite adequate treatment with metoprolol) Chronic or paroxysmal Atrial Fibrillation Presence or scheduled coronary revascularization procedure History of myocardial infarction or stroke. Presence of Diabetes Mellitus. Known kidney disease or a Glomerular Filtration Rate (GFR)MDRD < 60 ml/min/1.73m2 Malignant disease (exception: treated basal-cell or squamous cell carcinoma). Use of Vitamin K antagonists. A life-expectancy < 2 years Pregnancy or wish to become pregnant in the near future.

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: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Quadruple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Vitamin K2 supplementation<br> | Dietary Supplement: Menaquinone-7 (Vitamin K2)<br>* Menaquinone-7 (Vitamin K2)<br>|
| Placebo Comparator: Placebo control<br> | Other: Placebo capsules<br>* Capsules containing no Menaquinone-7<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Coronary Artery Calcification-score progression |  | 12 and 24 months | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Arterial Stiffness measured by Carotid-Femoral Pulse-Wave Velocity |  | 0, 12 and 24 months | 
| Carotid Intima Media Thickness |  | 0, 12 and 24 months | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Coronary Artery Calcification, Vitamin K, Trial, Treatment