<clinical_study>
  <!-- This xml conforms to an XML Schema at:
    https://clinicaltrials.gov/ct2/html/images/info/public.xsd -->
  <required_header>
    <download_date>ClinicalTrials.gov processed this data on September 20, 2023</download_date>
    <link_text>Link to the current ClinicalTrials.gov record.</link_text>
    <url>https://clinicaltrials.gov/ct2/show/NCT04429035</url>
  </required_header>
  <id_info>
    <org_study_id>55461</org_study_id>
    <nct_id>NCT04429035</nct_id>
  </id_info>
  <brief_title>SLOW-Slower Progress of caLcificatiOn With Vitamin K2</brief_title>
  <official_title>Inhibition of Aortic Valve Calcification Through the Carboxylation Mechanism of Matrix Gla Protein (MGP), Following Administration of Vitamin K2 (Menaquinone-7). Correlation With Mitral Annulus and Ascending Aorta Calcification.</official_title>
  <sponsors>
    <lead_sponsor>
      <agency>National and Kapodistrian University of Athens</agency>
      <agency_class>Other</agency_class>
    </lead_sponsor>
  </sponsors>
  <source>National and Kapodistrian University of Athens</source>
  <oversight_info>
    <has_dmc>No</has_dmc>
    <is_fda_regulated_drug>No</is_fda_regulated_drug>
    <is_fda_regulated_device>No</is_fda_regulated_device>
    <is_us_export>No</is_us_export>
  </oversight_info>
  <brief_summary>
    <textblock>
      A randomized 12-month trial will include two groups of 100 individuals aged over 50 years,&#xD;
      with asymptomatic mild to moderate Aortic valve stenosis (AVA &gt; 1 cm2, Vmax &lt; 4 m/s). The&#xD;
      first group of 100 individuals will serve as the intervention group that will receive 300 mcg&#xD;
      of K2 vitamin on a daily basis, while the second group of 100 individuals will be the control&#xD;
      group that will receive placebo on a daily basis as well. Both groups will be monitored&#xD;
      identically in order to investigate therapeutic effects on calcification and valve stenosis&#xD;
      progression. Correlation with Mitral annulus and ascending Aorta.Exclusion criteria: Chronic&#xD;
      Kidney disease, Vitamin K antagonists, statins, age &lt; 50 y.o,prosthetic valves,Aortic Valve&#xD;
      area (AVA) &lt; 1cm2 ,Vmax &gt; 4 m/s&#xD;
    </textblock>
  </brief_summary>
  <detailed_description>
    <textblock>
      For the purposes of this study, all individuals will be subjected to the same quantitative&#xD;
      and qualitative tests, before and after the daily administration of 300mcg K2 vitamin/placebo&#xD;
      for a period of one year.Clinical examination,extensive blood laboratory tests,direct&#xD;
      measurement of Dephosphorylated-uncarboxylated MGP(dp-ucMGP), Echocardiogram and ECS,carotid&#xD;
      ultrasound,ophthalmologic exam,further imaging methods with MSCT Calcium Score(Agatston&#xD;
      score) will take place.Correlations with their medical and pharmacological therapy history.&#xD;
&#xD;
      Before and after the administration of VK2/placebo, the following measurements will take&#xD;
      place i)Quantitative and percentile rate determination of Aortic Valve, Mitral Valve and&#xD;
      Ascending Aorta calcification via MSCT Calcium score without contrast.&#xD;
&#xD;
      ii)Echocardiogram and calcification evaluation via Echocardiographic Calcium Score (ECS),&#xD;
      iii)Determination of changes in carotid intima-media thickness (cIMT) and Carotid stenosis&#xD;
      iv)Standard ophthalmologic examination v)Direct measurement of&#xD;
      Dephosphorylated-uncarboxylated MGP(dp-ucMGP) vi)Correlation with blood biomarkers&#xD;
    </textblock>
  </detailed_description>
  <overall_status>Recruiting</overall_status>
  <start_date type="Actual">September 23, 2019</start_date>
  <completion_date type="Anticipated">December 23, 2023</completion_date>
  <primary_completion_date type="Anticipated">October 23, 2022</primary_completion_date>
  <phase>N/A</phase>
  <study_type>Interventional</study_type>
  <has_expanded_access>No</has_expanded_access>
  <study_design_info>
    <allocation>Randomized</allocation>
    <intervention_model>Parallel Assignment</intervention_model>
    <primary_purpose>Treatment</primary_purpose>
    <masking>Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)</masking>
  </study_design_info>
  <primary_outcome>
    <measure>Evaluation of calcification change of Aortic valve.Correlation With Mitral annulus and ascending Aorta calcification.A randomized 12-month trial.</measure>
    <time_frame>Each patient will be evaluated twice a year.Once before the administartion of VK2/Placebo and after a period of a 12 month administration of VK2/PLACEBO</time_frame>
    <description>The calcification change will be evaluated via a 64 MSCT scanner measuring the calcium via Agatston score, before and after administration of VK2/placebo.The following measurements will take place and after 12 months will be compared.</description>
  </primary_outcome>
  <number_of_arms>2</number_of_arms>
  <enrollment type="Anticipated">200</enrollment>
  <condition>Aortic Valve Stenosis</condition>
  <condition>Aortic Valve Calcification</condition>
  <condition>Mitral Annular Calcification</condition>
  <condition>Mitral Valve Calcification</condition>
  <condition>Mitral Valve Stenosis</condition>
  <arm_group>
    <arm_group_label>Vitamin K2</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>Participants receive Vitamin K2 (Menaquinone) 100mcg tablet orally 3 times daily for 12 months.</description>
  </arm_group>
  <arm_group>
    <arm_group_label>Placebo</arm_group_label>
    <arm_group_type>Placebo Comparator</arm_group_type>
    <description>Participants receive Vitamin K2 (Menaquinone) placebo tablet matching Vitamin K2 (Menaquinone) orally 3 times daily for 12 months.</description>
  </arm_group>
  <intervention>
    <intervention_type>Dietary Supplement</intervention_type>
    <intervention_name>Vitamin K2</intervention_name>
    <description>Administration of 300 μg Vitamin K2 (MQ7) daily p.o</description>
    <arm_group_label>Vitamin K2</arm_group_label>
  </intervention>
  <intervention>
    <intervention_type>Dietary Supplement</intervention_type>
    <intervention_name>Placebo</intervention_name>
    <description>Administration of 300 μg Vitamin K2 (MQ7) Placebo daily p.o</description>
    <arm_group_label>Placebo</arm_group_label>
  </intervention>
  <eligibility>
    <criteria>
      <textblock>
        Inclusion Criteria:&#xD;
&#xD;
          -  ASYMPTOMATIC AV STENOSIS WITH AVA&gt;1 cm2 &amp; Vmax&lt;4m/s&#xD;
&#xD;
        Exclusion Criteria:&#xD;
&#xD;
          -  AVK,STATINS,MSCT THE LAST 6 MONTHS,PROSTHETIC VALVES, AVA&lt;1 cm2,Vmax&gt;4m/s&#xD;
      </textblock>
    </criteria>
    <gender>All</gender>
    <minimum_age>50 Years</minimum_age>
    <maximum_age>N/A</maximum_age>
    <healthy_volunteers>Accepts Healthy Volunteers</healthy_volunteers>
  </eligibility>
  <overall_contact>
    <last_name>Symeon Evangelos Mavroudeas, MD</last_name>
    <phone>00306948694644</phone>
    <email>akis-m@hotmail.com</email>
  </overall_contact>
  <overall_contact_backup>
    <last_name>Konstantinos P Toutouzas, Professor</last_name>
  </overall_contact_backup>
  <location>
    <facility>
      <name>First Department of Cardiology, University of Athens</name>
      <address>
        <city>Athens</city>
        <state>Attiki</state>
        <zip>11527</zip>
        <country>Greece</country>
      </address>
    </facility>
    <status>Recruiting</status>
    <contact>
      <last_name>Konstantinos P Toutouzas, Professor</last_name>
      <phone>00302132088147</phone>
      <email>ktoutouz@gmail.com</email>
    </contact>
    <contact_backup>
      <last_name>Symeon Evangelos Mavroudeas, MD</last_name>
      <phone>00306948694644</phone>
      <email>akis-m@hotmail.com</email>
    </contact_backup>
  </location>
  <location>
    <facility>
      <name>Hippokration Hospital 1st Department of Cardiology,National and Kapodistrian University of Athens,Medical School</name>
      <address>
        <city>Athens</city>
        <state>Attiki</state>
        <zip>11527</zip>
        <country>Greece</country>
      </address>
    </facility>
    <status>Recruiting</status>
  </location>
  <location_countries>
    <country>Greece</country>
  </location_countries>
  <verification_date>August 2021</verification_date>
  <study_first_submitted>May 31, 2020</study_first_submitted>
  <study_first_submitted_qc>June 9, 2020</study_first_submitted_qc>
  <study_first_posted type="Actual">June 11, 2020</study_first_posted>
  <last_update_submitted>August 31, 2021</last_update_submitted>
  <last_update_submitted_qc>August 31, 2021</last_update_submitted_qc>
  <last_update_posted type="Actual">September 1, 2021</last_update_posted>
  <responsible_party>
    <responsible_party_type>Principal Investigator</responsible_party_type>
    <investigator_affiliation>National and Kapodistrian University of Athens</investigator_affiliation>
    <investigator_full_name>Konstantinos Toutouzas</investigator_full_name>
    <investigator_title>Professor of Cardiology</investigator_title>
  </responsible_party>
  <condition_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Aortic Valve Stenosis</mesh_term>
    <mesh_term>Mitral Valve Stenosis</mesh_term>
    <mesh_term>Calcinosis</mesh_term>
    <mesh_term>Constriction, Pathologic</mesh_term>
  </condition_browse>
  <intervention_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Vitamin K</mesh_term>
    <mesh_term>Vitamin K 2</mesh_term>
  </intervention_browse>
  <!-- Results have not yet been posted for this study                                          -->
</clinical_study>


download date: ClinicalTrials.gov processed this data on September 20, 2023
link text: Link to the current ClinicalTrials.gov record.
url: https://clinicaltrials.gov/ct2/show/NCT04429035
org study id: 55461
nct id: NCT04429035
lead sponsor: 
has dmc: No
is fda regulated drug: No
is fda regulated device: No
is us export: No
A randomized 12-month trial will include two groups of 100 individuals aged over 50 years,
      with asymptomatic mild to moderate Aortic valve stenosis (AVA > 1 cm2, Vmax < 4 m/s). The
      first group of 100 individuals will serve as the intervention group that will receive 300 mcg
      of K2 vitamin on a daily basis, while the second group of 100 individuals will be the control
      group that will receive placebo on a daily basis as well. Both groups will be monitored
      identically in order to investigate therapeutic effects on calcification and valve stenosis
      progression. Correlation with Mitral annulus and ascending Aorta.Exclusion criteria: Chronic
      Kidney disease, Vitamin K antagonists, statins, age < 50 y.o,prosthetic valves,Aortic Valve
      area (AVA) < 1cm2 ,Vmax > 4 m/s
For the purposes of this study, all individuals will be subjected to the same quantitative
      and qualitative tests, before and after the daily administration of 300mcg K2 vitamin/placebo
      for a period of one year.Clinical examination,extensive blood laboratory tests,direct
      measurement of Dephosphorylated-uncarboxylated MGP(dp-ucMGP), Echocardiogram and ECS,carotid
      ultrasound,ophthalmologic exam,further imaging methods with MSCT Calcium Score(Agatston
      score) will take place.Correlations with their medical and pharmacological therapy history.

      Before and after the administration of VK2/placebo, the following measurements will take
      place i)Quantitative and percentile rate determination of Aortic Valve, Mitral Valve and
      Ascending Aorta calcification via MSCT Calcium score without contrast.

      ii)Echocardiogram and calcification evaluation via Echocardiographic Calcium Score (ECS),
      iii)Determination of changes in carotid intima-media thickness (cIMT) and Carotid stenosis
      iv)Standard ophthalmologic examination v)Direct measurement of
      Dephosphorylated-uncarboxylated MGP(dp-ucMGP) vi)Correlation with blood biomarkers
allocation: Randomized
intervention model: Parallel Assignment
primary purpose: Treatment
masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
measure: Evaluation of calcification change of Aortic valve.Correlation With Mitral annulus and ascending Aorta calcification.A randomized 12-month trial.
time frame: Each patient will be evaluated twice a year.Once before the administartion of VK2/Placebo and after a period of a 12 month administration of VK2/PLACEBO
description: The calcification change will be evaluated via a 64 MSCT scanner measuring the calcium via Agatston score, before and after administration of VK2/placebo.The following measurements will take place and after 12 months will be compared.
arm group label: Vitamin K2
arm group type: Experimental
description: Participants receive Vitamin K2 (Menaquinone) 100mcg tablet orally 3 times daily for 12 months.
arm group label: Placebo
arm group type: Placebo Comparator
description: Participants receive Vitamin K2 (Menaquinone) placebo tablet matching Vitamin K2 (Menaquinone) orally 3 times daily for 12 months.
intervention type: Dietary Supplement
intervention name: Vitamin K2
description: Administration of 300 μg Vitamin K2 (MQ7) daily p.o
arm group label: Vitamin K2
intervention type: Dietary Supplement
intervention name: Placebo
description: Administration of 300 μg Vitamin K2 (MQ7) Placebo daily p.o
arm group label: Placebo
criteria: 
gender: All
minimum age: 50 Years
maximum age: N/A
healthy volunteers: Accepts Healthy Volunteers
last name: Symeon Evangelos Mavroudeas, MD
phone: 00306948694644
email: akis-m@hotmail.com
last name: Konstantinos P Toutouzas, Professor
facility: 
status: Recruiting
contact: 
contact backup: 
facility: 
status: Recruiting
country: Greece
responsible party type: Principal Investigator
investigator affiliation: National and Kapodistrian University of Athens
investigator full name: Konstantinos Toutouzas
investigator title: Professor of Cardiology
mesh term: Aortic Valve Stenosis
mesh term: Mitral Valve Stenosis
mesh term: Calcinosis
mesh term: Constriction, Pathologic
mesh term: Vitamin K
mesh term: Vitamin K 2