Bicuspid Aortic Valve Stenosis and the Effect of vItamin K2 on Calciummetabolism on 18F-NaF PET/MRI

Study Overview
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Brief Summary
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Early development of calcified aortic valve disease (CAVD) is a commonly occurring complication in patients with a bicuspid aortic valve (BAV, an aortic valve consisting of two leaflets instead of three). In general, CAVD is characterized by progressive narrowing of the aortic valve, with involvement of altered calcium metabolism. CAVD progression in fact may lead to necessity of valve replacement, since to date, no other therapies have been shown effective in the treatment of CAVD. The primary objective of our study is to test the hypothesis that supplementation of vitamin K2 will slow down the calcium metabolism in CAVD. Vitamin K2 is essential in the activation of matrix Gla Protein (MGP), an important inhibitory factor in the regulation of calcification. In this randomized controlled trial, 44 patients will be allocated to either the vitamin K2 or placebo group. To assess the calcification process in a detailed manner in these patients, a Positron Emission Tomography (PET) scanner using a tracer (18F-fluoride [NaF]) that has been shown to bind to regions of newly developing microcalcification in aortic valve tissue is used. We expect that vitamin K2 supplementation will reduce the calcium metabolism in the aortic valve on 18NaF-PET (primary endpoint) and slow progression of CAVD as measured by the calcium score on CT and echocardiography after 18 months (secondary endpoints), when compared to placebo.

Official Title
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Bicuspid Aortic Valve Stenosis and the Effect of vItamin K2 on Calciummetabolism on 18F-NaF PET/MRI (BASIK2): a Pilot Study

Conditions
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Aortic Valve Stenosis, Bicuspid Aortic Valve

Intervention / Treatment
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* Dietary Supplement: Vitamin K2
* Other: Placebo


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: known bicuspid aortic valve calcified mild to moderate aortic valve stenosis on prior echocardiography informed consent provided Exclusion Criteria: absence of calcified aortic valve stenosis on echocardiography presence of severe aortic valve stenosis history of aortic valve repair or replacement accepted atrial fibrillation use of oral anticoagulants claustrophobia presence of a pacemaker, ICD or ferromagnetic materials in the body life expectancy <2 years Pregnancy (current or wish for near future) soy allergy use of vitamin K-containing supplements

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<br>22 patients will receive 360ug Vitamin K2 daily during 18 months. | Dietary Supplement: Vitamin K2<br> <br> |
| Placebo Comparator: Placebo<br>22 patients will receive placebo during 18 months. | Other: Placebo<br> <br> |

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Change in aortic valve calcium metabolism | Change in calcium metabolism, measured as uptake of the 18F-NaF tracer on a 18F-NaF PET/CMR scan | Measured at baseline and 6 months | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Change in aortic valve calcium score | Change in aortic valve calcium score, measured on CT. | Measured at baseline, 6 and 18 months | 
| Progression of aortic valve stenosis | Change of severity of aortic valve stenosis on echocardiography | Measured at baseline, 6, 12 and 18 months | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Calcium metabolism, Matrix Gla Protein, Vitamin K2