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

Phase 2

• Conditions: Bicuspid Aortic Valve; Aortic Valve Stenosis
• Interventions: Dietary Supplement: Vitamin K2; Other: Placebo

• Registration Number: NCT02917525
• Lead Sponsor: Maastricht University Medical Center

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.

Detailed Description

Not available

Study Timeline

• Study Start: 2016-08
• Study First Submitted: 2016-09-26
• Study First Submitted QC: 2016-09-26
• Study First Posted: 2016-09-28
• Status Verified: 2018-03
• Last Update Submitted: 2018-03-21
• Last Update Posted: 2018-03-22
• Primary Completion: 2019-12
• Study Completion: 2019-12

Recruitment & Eligibility

• Status: UNKNOWN
• Sex: All
• Target Recruitment: 44

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

Study & Design

• Study Type: INTERVENTIONAL
• Study Design: PARALLEL

Arm && Interventions

Group	Intervention	Description
Vitamin K2	Vitamin K2	22 patients will receive 360ug Vitamin K2 daily during 18 months.
Placebo	Placebo	22 patients will receive placebo during 18 months.

Primary Outcome Measures

Name	Time	Method
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 Outcome Measures

Name	Time	Method
Progression of aortic valve stenosis	Measured at baseline, 6, 12 and 18 months	Change of severity of aortic valve stenosis on echocardiography
Change in aortic valve calcium score	Measured at baseline, 6 and 18 months	Change in aortic valve calcium score, measured on CT.

Trial Locations

Locations (1)

Maastricht UMC; 🇳🇱 Maastricht, Netherlands