NCT02917525

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.

Trial Health

43
At Risk

Trial Health Score

Automated assessment based on enrollment pace, timeline, and geographic reach

Trial has exceeded expected completion date
Enrollment
44

participants targeted

Target at P25-P50 for phase_2

Timeline
Completed

Started Aug 2016

Typical duration for phase_2

Geographic Reach
1 country

1 active site

Status
unknown

Health score is calculated from publicly available data and should be used for screening purposes only.

Trial Relationships

Click on a node to explore related trials.

Study Timeline

Key milestones and dates

Study Start

First participant enrolled

August 1, 2016

Completed
2 months until next milestone

First Submitted

Initial submission to the registry

September 26, 2016

Completed
2 days until next milestone

First Posted

Study publicly available on registry

September 28, 2016

Completed
3.2 years until next milestone

Primary Completion

Last participant's last visit for primary outcome

December 1, 2019

Completed
Same day until next milestone

Study Completion

Last participant's last visit for all outcomes

December 1, 2019

Completed
Last Updated

March 22, 2018

Status Verified

March 1, 2018

Enrollment Period

3.3 years

First QC Date

September 26, 2016

Last Update Submit

March 21, 2018

Conditions

Aortic Valve StenosisBicuspid Aortic Valve

Keywords

Calcium metabolismMatrix Gla ProteinVitamin K2

Outcome Measures

Primary Outcomes (1)

  • 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 Outcomes (2)

  • Change in aortic valve calcium score

    Measured at baseline, 6 and 18 months

  • Progression of aortic valve stenosis

    Measured at baseline, 6, 12 and 18 months

Study Arms (2)

Vitamin K2

EXPERIMENTAL

22 patients will receive 360ug Vitamin K2 daily during 18 months.

Dietary Supplement: Vitamin K2

Placebo

PLACEBO COMPARATOR

22 patients will receive placebo during 18 months.

Other: Placebo

Interventions

Vitamin K2DIETARY_SUPPLEMENT
Vitamin K2
PlaceboOTHER
Placebo

Eligibility Criteria

Age18 Years+
Sexall
Healthy VolunteersNo
Age GroupsAdult (18-64), Older Adult (65+)

You may qualify if:

  • known bicuspid aortic valve
  • calcified mild to moderate aortic valve stenosis on prior echocardiography
  • informed consent provided

You may not qualify if:

  • 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

Contact the study team to confirm eligibility.

Sponsors & Collaborators

Study Sites (1)

Maastricht UMC

Maastricht, 6202 AZ, Netherlands

RECRUITING

MeSH Terms

Conditions

Aortic Valve StenosisBicuspid Aortic Valve Disease

Interventions

Vitamin K 2

Condition Hierarchy (Ancestors)

Aortic Valve DiseaseHeart Valve DiseasesHeart DiseasesCardiovascular DiseasesVentricular Outflow ObstructionHeart Defects, CongenitalCardiovascular AbnormalitiesCongenital AbnormalitiesCongenital, Hereditary, and Neonatal Diseases and Abnormalities

Intervention Hierarchy (Ancestors)

Vitamin KNaphthoquinonesNaphthalenesPolycyclic Aromatic HydrocarbonsHydrocarbons, AromaticHydrocarbons, CyclicHydrocarbonsOrganic ChemicalsPhytolDiterpenesTerpenesQuinonesPolycyclic Compounds

Study Officials

  • Bas Kietselaer, M.D. PhD

    Maastricht UMC

    PRINCIPAL INVESTIGATOR

Central Study Contacts

Bas Kietselaer, M.D., PhD

CONTACT

+31 (0)43 687 5096b.kietselaer@mumc.nl

Study Design

Study Type
interventional
Phase
phase 2
Allocation
RANDOMIZED
Masking
QUADRUPLE
Who Masked
PARTICIPANT, CARE PROVIDER, INVESTIGATOR, OUTCOMES ASSESSOR
Purpose
TREATMENT
Intervention Model
PARALLEL
Sponsor Type
OTHER
Responsible Party
SPONSOR

Study Record Dates

First Submitted

September 26, 2016

First Posted

September 28, 2016

Study Start

August 1, 2016

Primary Completion

December 1, 2019

Study Completion

December 1, 2019

Last Updated

March 22, 2018

Record last verified: 2018-03

Locations

NL(1)