To test the hypothesis that supplementation with vitamin K2 in comparison to placebo (total duration of treatment: 18 months) will slow down aortic valve calcium metabolism (on18F-NaF PET/MRI) after 6 months in subjects with a bicuspid aortic valve…
ID
Source
Brief title
Condition
- Cardiac valve disorders
- Cardiac and vascular disorders congenital
Synonym
Research involving
Sponsors and support
Intervention
Outcome measures
Primary outcome
The primary endpoint of the study is the difference in (the mean of) the
maximal uptake of 18F-NaF tracer of the aortic valve between the intervention
group and the control group after 6 months on 18F-NaF PET/CMR-scan.
Secondary outcome
Secondary endpoints include the difference in mean calcium mass score
progression of the aortic valve between the intervention group and the control
group after 6 and 18 months on non-contrast CT-scan, whether the primary
endpoint predicts or correlates with the results in calcium mass score after 6
and 18 months, whether supplementation with Vitamin K2 reduces progression of
aortic valve stenosis, whether it is associated with altered aortic
distensibility and flow, whether it is associated with reduced impairment of
left ventricular (LV) function, whether serum biomarker values might predict
long term diastolic function and whether more AVRs occur in the control group.
Background summary
A bicuspid aortic valve (BAV, an aortic valve consisting of two leaflets
instead of three) is a common congenital abnormality, occurring in 1-2% of the
general population. BAV disease has a very heterogeneous clinical presentation,
and occurrence and progression of complications is difficult to predict.
Complications most often occurring in BAV are of valvular and vascular nature.
Early development of calcified aortic valve disease (CAVD) is one of the most
commonly occurring complications. 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.
Matrix Gla Protein (MGP) is a Vitamin K dependent protein known as an important
inhibitory factor in the regulation of calcification. In humans, treatment with
vitamin K antagonists results in more valve calcification, indicating the
importance of Vitamin K and MGP level. Moreover, supplementation of the
food-supplement vitamin K2 (menaquinone) in rats, resulted in regression of
arterial calcifications. Although these results support the hypothesis that
Vitamin K2 has a inhibitory effect on calcification, no controlled trials exist
assessing the effects of the food-supplement Vitamin K2 supplementation on
arterial and valvular calcification.
Study objective
To test the hypothesis that supplementation with vitamin K2 in comparison to
placebo (total duration of treatment: 18 months) will slow down aortic valve
calcium metabolism (on18F-NaF PET/MRI) after 6 months in subjects with a
bicuspid aortic valve and mild to moderate calcified aortic valve stenosis..
Study design
A prospective, double-blind randomized controlled trial with one group
receiving Vitamin K2 and one group receiving placebo for 18 months.
Intervention
Subjects randomized in the intervention group will receive an oral dose of 360
ug vitamin K2 (menaquinone 7) daily. Subjects randomized in the control group
will receive placebo that is identical to the supplement in the intervention
group, without MK-7 though. Both subjects and researchers will be blinded to
the treatment allocation of subjects.
Study burden and risks
the duration of follow-up is 18 months and patients will visit the outpatient
clinic after 6, 12 and 18 months. During these visits, drug-compliance is
monitored, an echocardiography will be performed and blood samples will be
obtained through standard venipuncture. At baseline and after 6 months, a
18F-NaF PET/CMR-scan will be performed in order to assess calcium metabolism of
the aortic valve. Moreover, valvular function and aortic dimensions will be
determined. Also, a calcium score will be determined by non-contrast CT at
baseline and after 18 months, in order to assess changes valvular
calcification.
No side effects have been reported in subjects using vitamin K2 in a daily dose
of 360 ug. Vitamin K2 supplementation does not induce or increase a
hypercoagulable state. The average effective radiation dose using this
technique of CT-scan is 0.3 mSv and 3.5 mSv for the PET-CMR. The investigation
will take 120 minutes including preparation and there has to be venous access
for the infusion of the radiolabeled 18F-NaF. Furthermore, patients should not
be claustrophobic since the scanner has a relatively narrow bore (60 cm).A
total of 24 ml blood will be obtained each study visit. Blood samples will be
obtained by venipuncture, which might cause a local hematoma.
P. Debyelaan 25
Maastricht 6229 HX
NL
P. Debyelaan 25
Maastricht 6229 HX
NL
Listed location countries
Age
Inclusion criteria
Known with a bicuspid aortic valve and,
Calcified mild to moderate aortic valve stenosis on prior echocardiography
Age older than 18 years
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 aortic valve replacement , scheduled for aortic valve replacement or repair , accepted atrial fibrillation, use of oral anticoagulants, claustrophobia, presence of a pacemaker or ICD or ferromagnetic materials in the body, adipositas permagna, history of (non treated) cancer within the previous two years (excep non-melanoma skin cancer, carcinomas or in situ carcinoma of cervix), life expectancy of less than 2 years, wish for near future, or present pregnancy, breast feeding, (active) metabolic or gastrointestinal disease not controlled by current treatment, (history of) soy allergy, use of vitamin K-containing supplements, chronic inflammatory disease, systemic treatment or topical treatment likely to interfere with evaluation of the study parameters, corticoid treatment, participation in a clinical study more recently than one month before the current study.
Design
Recruitment
Followed up by the following (possibly more current) registration
No registrations found.
Other (possibly less up-to-date) registrations in this register
No registrations found.
In other registers
| Register | ID |
|---|---|
| CCMO | NL54600.068.15 |