Clinical trial NCT02917525: Bicuspid Aortic Valve Stenosis and the Effect of vItamin K2 on Calciummetabolism on 18F-NaF PET/MRI
Official title: Bicuspid Aortic Valve Stenosis and the Effect of vItamin K2 on Calciummetabolism on 18F-NaF PET/MRI (BASIK2): a Pilot Study
Study type: INTERVENTIONAL
Overall status: UNKNOWN
Phase: PHASE2
Conditions: Aortic Valve Stenosis
Bicuspid Aortic Valve
Keywords: Calcium metabolism
Matrix Gla Protein
Vitamin K2
Lead sponsor: Maastricht University Medical Center
Sponsor class: OTHER
First posted: 2016-09-28
Enrollment: 44
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

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.


Eligibility criteria: 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

Primary outcomes:
measure: Change in aortic valve calcium metabolism
timeFrame: Measured at baseline and 6 months
Secondary outcomes:
measure: Change in aortic valve calcium score
timeFrame: Measured at baseline, 6 and 18 months
measure: Progression of aortic valve stenosis
timeFrame: Measured at baseline, 6, 12 and 18 months
Other outcomes:
Locations:
city: Maastricht
country: Netherlands
facility: Maastricht UMC
Study officials:
affiliation: Maastricht UMC
name: Bas Kietselaer, M.D. PhD
role: PRINCIPAL_INVESTIGATOR
References: