Effects of Combined Vitamin K2 and Vitamin D3 Supplementation on Na[18F]F PET/MRI in Patients with Carotid Artery Disease: The INTRICATE Rationale and Trial Design

Alexandru Florea, M Eline Kooi, Werner Mess, Leon J Schurgers, Jan Bucerius, Felix M Mottaghy*

*Corresponding author for this work

Research output: Contribution to journalArticleAcademicpeer-review

1 Citation (Web of Science)


INTRICATE is a prospective double-blind placebo-controlled feasibility study, assessing the influence of combined vitamin K2 and vitamin D3 supplementation on micro-calcification in carotid artery disease as imaged by hybrid Sodium [18F]Fluoride (Na[18F]F) positron emission tomography (PET)/ magnetic resonance imaging (MRI). Arterial calcification is an actively regulated process and results from the imbalance between calcification promoting and inhibiting factors. Considering the recent advancements in medical imaging, ultrasound (US), PET/MRI, and computed tomography (CT) can be used for the selection and stratification of patients with atherosclerosis. Fifty-two subjects with asymptomatic carotid artery disease on at least one side of the neck will be included in the study. At baseline, an Na[18F]F PET/MRI and CT examination will be performed. Afterwards, subjects will be randomized (1:1) to a vitamin K (400 µg MK-7/day) and vitamin D3 (80 µg/day) or to placebo. At the 3-month follow-up, subjects will undergo a second Na[18F]F PET/MRI and CT scan. The primary endpoint is the change in Na[18F]F PET/MRI (baseline vs. after 3 months) in the treatment group as compared to the placebo arm. Secondary endpoints are changes in plaque composition and in blood-biomarkers. The INTRICATE trial bears the potential to open novel avenues for future large scale randomized controlled trials to intervene in the plaque development and micro-calcification progression.

Original languageEnglish
Article number994
Number of pages12
Issue number3
Publication statusPublished - 19 Mar 2021


  • Atherosclerosis/drug therapy
  • Calcinosis/diagnostic imaging
  • Carotid Artery Diseases/diagnosis
  • Cholecalciferol/pharmacology
  • Dietary Supplements
  • Double-Blind Method
  • Fluorides
  • Positron-Emission Tomography/methods
  • Prospective Studies
  • Sodium Fluoride
  • Tomography, X-Ray Computed
  • Vitamin K 2/pharmacology
  • magnetic resonance imaging
  • vitamin D
  • vascular calcification
  • cardiovascular diseases
  • vitamin K
  • sodium fluoride
  • micro-calcification
  • positron emission tomography

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