Aortic Valve Stenosis, Bicuspid Aortic Valve
Conditions
Keywords
Calcium metabolism, Matrix Gla Protein, Vitamin K2
Brief summary
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.
Interventions
DIETARY_SUPPLEMENTVitamin K2
OTHERPlacebo
Sponsors
Maastricht University Medical Center
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
QUADRUPLE (Subject, Caregiver, Investigator, Outcomes Assessor)
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
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
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Change in aortic valve calcium metabolism | Measured at baseline and 6 months | Change in calcium metabolism, measured as uptake of the 18F-NaF tracer on a 18F-NaF PET/CMR scan |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Change in aortic valve calcium score | Measured at baseline, 6 and 18 months | Change in aortic valve calcium score, measured on CT. |
| Progression of aortic valve stenosis | Measured at baseline, 6, 12 and 18 months | Change of severity of aortic valve stenosis on echocardiography |
Countries
Netherlands
Contacts
Primary ContactBas Kietselaer, M.D., PhD
Outcome results
None listed