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

Primary Purpose

Coronary Artery Disease, Carotid Artery Disease

Status
Not yet recruiting
Phase
Not Applicable
Locations
Study Type
Interventional
Intervention
MK-7 and vitamin D3
Placebo
Sponsored by
Academisch Ziekenhuis Maastricht
About
Eligibility
Locations
Arms
Outcomes
Full info

About this trial

This is an interventional treatment trial for Coronary Artery Disease focused on measuring Vitamin K2, 18F-NaF, hybrid PET/MRI, Coronary artery calcification score, Menaquinone-7, Carotid Artery Disease, Coronary Artery Disease, Vitamin D3

Eligibility Criteria

18 Years - undefined (Adult, Older Adult)All SexesDoes not accept healthy volunteers

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

Sites / Locations

    Arms of the Study

    Arm 1

    Arm 2

    Arm Type

    Experimental

    Placebo Comparator

    Arm Label

    MK-7 and vitamin D3 supplementation

    Placebo

    Arm Description

    Patients will receive a daily MK-7 and vitamin D3 supplementation for 3 months.

    Patients will receive a daily placebo for 3 months.

    Outcomes

    Primary Outcome Measures

    The change in time of vascular micro-calcification via (18)F-NaF PET/MRI
    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

    The change in time of vascular calcification via coronary artery calcification score
    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 score
    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 parameters
    Investigating whether MK-7 and vitamin D3 supplementation can influence the fibrous cap status on the MRI.

    Full Information

    First Posted
    July 1, 2019
    Last Updated
    September 20, 2023
    Sponsor
    Academisch Ziekenhuis Maastricht
    Collaborators
    Horizon 2020 - European Commission
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    1. Study Identification

    Unique Protocol Identification Number
    NCT04010578
    Brief Title
    Effects of VitamIN K2 and D3 supplementaTion on PET/MRI in Carotid Artery Disease
    Acronym
    INTRICATE
    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

    2. Study Status

    Record Verification Date
    September 2023
    Overall Recruitment Status
    Not yet recruiting
    Study Start Date
    January 1, 2024 (Anticipated)
    Primary Completion Date
    January 1, 2025 (Anticipated)
    Study Completion Date
    April 1, 2025 (Anticipated)

    3. Sponsor/Collaborators

    Responsible Party, by Official Title
    Principal Investigator
    Name of the Sponsor
    Academisch Ziekenhuis Maastricht
    Collaborators
    Horizon 2020 - European Commission

    4. Oversight

    Studies a U.S. FDA-regulated Drug Product
    No
    Studies a U.S. FDA-regulated Device Product
    No
    Data Monitoring Committee
    No

    5. Study Description

    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.

    6. Conditions and Keywords

    Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
    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

    7. Study Design

    Primary Purpose
    Treatment
    Study Phase
    Not Applicable
    Interventional Study Model
    Parallel Assignment
    Model Description
    One group will receive a MK-7 and vitamin D3 supplementation and the control group will receive a placebo.
    Masking
    ParticipantCare ProviderInvestigatorOutcomes Assessor
    Allocation
    Randomized
    Enrollment
    52 (Anticipated)

    8. Arms, Groups, and Interventions

    Arm Title
    MK-7 and vitamin D3 supplementation
    Arm Type
    Experimental
    Arm Description
    Patients will receive a daily MK-7 and vitamin D3 supplementation for 3 months.
    Arm Title
    Placebo
    Arm Type
    Placebo Comparator
    Arm Description
    Patients will receive a daily placebo for 3 months.
    Intervention Type
    Dietary Supplement
    Intervention Name(s)
    MK-7 and vitamin D3
    Intervention Description
    Patients will receive 400 micro-grams of Menaquinone-7 and 80 micro-grams of vitamin D3 per day.
    Intervention Type
    Other
    Intervention Name(s)
    Placebo
    Intervention Description
    Patients will receive a placebo each day.
    Primary Outcome Measure Information:
    Title
    The change in time of vascular micro-calcification via (18)F-NaF PET/MRI
    Description
    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.
    Time Frame
    3 months follow-up
    Secondary Outcome Measure Information:
    Title
    The change in time of vascular calcification via coronary artery calcification score
    Description
    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.
    Time Frame
    3 months follow-up
    Title
    The correlation between (18)F-NaF PET/MRI and coronary artery calcification score
    Description
    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.
    Time Frame
    3 months follow-up
    Title
    The influence of MK-7 and vitamin D3 supplementation on MRI parameters
    Description
    Investigating whether MK-7 and vitamin D3 supplementation can influence the fibrous cap status on the MRI.
    Time Frame
    baseline vs 3 months follow-up
    Other Pre-specified Outcome Measures:
    Title
    The influence of MK-7 and vitamin D3 supplementation on carotid intima-media thickness
    Description
    Investigating whether MK-7 and vitamin D3 supplementation can influence the carotid intima-media thickness
    Time Frame
    baseline vs 3 months follow-up

    10. Eligibility

    Sex
    All
    Minimum Age & Unit of Time
    18 Years
    Accepts Healthy Volunteers
    No
    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
    Central Contact Person:
    First Name & Middle Initial & Last Name or Official Title & Degree
    Felix M Mottaghy, MD, PhD
    Phone
    +31 43 3874746
    Email
    felix.mottaghy@mumc.nl
    First Name & Middle Initial & Last Name or Official Title & Degree
    Alexandru Florea, MD
    Phone
    +49 241 80 89584
    Email
    aflorea@ukaachen.de
    Overall Study Officials:
    First Name & Middle Initial & Last Name & Degree
    Felix M Mottaghy, MD, PhD
    Organizational Affiliation
    Maastricht University Medical Center
    Official's Role
    Principal Investigator

    12. IPD Sharing Statement

    Plan to Share IPD
    Yes
    IPD Sharing Plan Description
    All IPD that underlie results in a publication will be shared.
    IPD Sharing Time Frame
    IPD will be shared stating with 6 months after publication.
    IPD Sharing Access Criteria
    Access criteria will be discussed with all the study members, then it will be published.

    Learn more about this trial

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

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