Clinical trial NCT04010578: Effects of VitamIN K2 and D3 supplementaTion on PET/MRI in Carotid Artery Disease
Official title: Effects of Vitamin K2 and D3 Supplementation on 18F-NaF PET/MRI in Patients With Carotid and Coronary Artery Disease
Study type: INTERVENTIONAL
Overall status: NOT_YET_RECRUITING
Phase: NA
Conditions: Coronary Artery Disease
Carotid Artery Disease
Keywords: Vitamin K2
18F-NaF
hybrid PET/MRI
Coronary artery calcification score
Menaquinone-7
Carotid Artery Disease
Coronary Artery Disease
Vitamin D3
Lead sponsor: Academisch Ziekenhuis Maastricht
Sponsor class: OTHER
Collaborators: name: Horizon 2020 - European Commission
First posted: 2019-07-08
Enrollment: 52
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Intervention model description: One group will receive a MK-7 and vitamin D3 supplementation and the control group will receive a placebo.
Primary purpose: TREATMENT

Brief summary: Atherosclerosis is a disease of the arteries and is the result of various factors such as high blood cholesterol or diabetes, which lead to accumulations of fats, cells, and calcium deposits (i.e. plaques). It has been shown that people with a rapid increase in the amount of calcium deposits have a higher risk for stroke and heart attack than people with a decreased amount.

Previous scientific research has shown that a protein called Matrix Gla Protein plays an important role in the prevention of calcification. This protein works well only if there is enough Vitamin K in the blood vessels. In a large human studies, it has been shown that especially MK-7 (a form of Vitamin K2) is best absorbed by blood vessels. Moreover, studies suggest positive effects of vitamin D (especially D3) on vitamin K-dependent metabolism.

Over the last years, fluorine-18 sodium fluoride (18F-NaF) positron emission tomography (PET) emerged as a reliable clinical imaging tool able to detect micro-calcification in the blood vessels. Therefore, the present study will use 18F-NaF PET in combination with magnetic resonance imaging (MRI) to assess the influence of vitamin K and D supplementation in the development of arterial micro-calcification in the context of atherosclerosis.

The present study would like to confirm that MK-7 and vitamin D3 supplementation induces a significant reduction in the degree of micro-calcification from carotid artery disease patients, when comparing to a placebo, after 3 months.

This will be a prospective double blind randomised controlled feasibility study, in which one group will receive a MK-7 and vitamin D3 supplementation compared to a control group receiving a placebo.


Eligibility criteria: Inclusion Criteria:

* Asymptomatic carotid artery disease on at least one side with a degree of stenosis \> 25% (according to on the ECST criteria). If the patient has a symptomatic carotid artery disease on the contra-lateral side, he/she will still be included in the study, if intensified medical treatment for this symptomatic stenosis (e.g. statins, antiplatelet medication) was started ≥ 6 month before inclusion of the patient. This protocol was chosen in order to widely assure a stable situation on the plaque(s), which avoids an overspill from this medication on the assumed effects of the MK-7 and vitamin D3 supplementation.
* Age older than 18 years
* Signed informed consent provided

Exclusion Criteria:

* Antiplatelet or cholesterol lowering medication started within the past 6 months
* Chronic or paroxysmal atrial fibrillation
* Presence or scheduled coronary or carotid revascularisation procedure (e.g. stent implantation, coronary artery bypass graft, balloon-dilatation, endarterectomy, angioplasty)
* History of myocardial infarction or stroke
* Malignant disease (except for treated basal-cell or squamous cell carcinoma)
* Use of vitamin K antagonists or any other anticoagulation treatment
* A life-expectancy \< 1 year
* Claustrophobia
* Presence of a pacemaker, intra-cardiac defibrillator, or metallic implant (e.g. vascular clip, neuro-stimulator, cochlear implant)
* Body weight \> 130kg or body habitus that does not fit into the gantry
* Pregnancy or wish to become pregnant in the near future
* Breast feeding
* (History of) metabolic or gastrointestinal disease
* Use of vitamin K or D containing supplements or vitamin K-rich foods (i.e. soya)
* 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

Primary outcomes:
measure: The change in time of vascular micro-calcification via (18)F-NaF PET/MRI
timeFrame: 3 months follow-up
Secondary outcomes:
measure: The change in time of vascular calcification via coronary artery calcification score
timeFrame: 3 months follow-up
measure: The correlation between (18)F-NaF PET/MRI and coronary artery calcification score
timeFrame: 3 months follow-up
measure: The influence of MK-7 and vitamin D3 supplementation on MRI parameters
timeFrame: baseline vs 3 months follow-up
Other outcomes:
measure: The influence of MK-7 and vitamin D3 supplementation on carotid intima-media thickness
timeFrame: baseline vs 3 months follow-up
Locations:
Study officials:
affiliation: Maastricht University Medical Center
name: Felix M Mottaghy, MD, PhD
role: PRINCIPAL_INVESTIGATOR
References: