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Effects of VitamIN K2 and D3 supplementaTion on PET/MRI in Carotid Artery Disease

Not Applicable
Not yet recruiting
Conditions
Carotid Artery Disease
Coronary Artery Disease
Interventions
Other: Placebo
Dietary Supplement: MK-7 and vitamin D3
Registration Number
NCT04010578
Lead Sponsor
Academisch Ziekenhuis Maastricht
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.

Detailed Description

Not available

Recruitment & Eligibility

Status
NOT_YET_RECRUITING
Sex
All
Target Recruitment
52
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

Study & Design

Study Type
INTERVENTIONAL
Study Design
PARALLEL
Arm && Interventions
GroupInterventionDescription
PlaceboPlaceboPatients will receive a daily placebo for 3 months.
MK-7 and vitamin D3 supplementationMK-7 and vitamin D3Patients will receive a daily MK-7 and vitamin D3 supplementation for 3 months.
Primary Outcome Measures
NameTimeMethod
The change in time of vascular micro-calcification via (18)F-NaF PET/MRI3 months follow-up

The primary outcome of this study is the mean rate of the change in time of vascular micro-calcification in the carotid arteries, measured as a difference between the intervention group and placebo group in (18)F-NaF uptake via hybrid PET/MRI after the 3 months of treatment.

Secondary Outcome Measures
NameTimeMethod
The change in time of vascular calcification via coronary artery calcification score3 months follow-up

Investigating whether MK-7 and vitamin D3 supplementation can diminish, halt or even reverse the development of arterial micro-calcification in the coronary arteries, measured as a difference between the intervention group and placebo group in coronary artery calcification score after the 3 months.

The Agatston coronary artery calcification score isis a semi-automated tool to calculate a score based on the extent of coronary artery calcification detected by an non-contrast low-dose CT scan. The score ranges from 0 arbitrary units to \> 400. The higher the value of the score, the higher the degree of calcification is in the coronary arteries; hence, lower values usually represent a better outcome.

The correlation between (18)F-NaF PET/MRI and coronary artery calcification score3 months follow-up

The correlation between the uptake of (18)F-NaF at 3 months and the coronary artery calcification score.

The Agatston coronary artery calcification score isis a semi-automated tool to calculate a score based on the extent of coronary artery calcification detected by an non-contrast low-dose CT scan. The score ranges from 0 arbitrary units to \> 400. The higher the value of the score, the higher the degree of calcification is in the coronary arteries; hence, lower values usually represent a better outcome.

The influence of MK-7 and vitamin D3 supplementation on MRI parametersbaseline vs 3 months follow-up

Investigating whether MK-7 and vitamin D3 supplementation can influence the fibrous cap status on the MRI.

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