<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/NCT03276377</url>
  </required_header>
  <id_info>
    <org_study_id>2017/19</org_study_id>
    <nct_id>NCT03276377</nct_id>
  </id_info>
  <brief_title>VItamin K Inhibition and NeurocoGnition (VIKING)</brief_title>
  <acronym>VIKING</acronym>
  <official_title>Use of Vitamin K Antagonist and Neurocognitive Disorders in Older Adults : a Retrospective Study With Exposed and Non-exposed Groups</official_title>
  <sponsors>
    <lead_sponsor>
      <agency>University Hospital, Angers</agency>
      <agency_class>Other</agency_class>
    </lead_sponsor>
  </sponsors>
  <source>University Hospital, Angers</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>
  </oversight_info>
  <brief_summary>
    <textblock>
      The primary objective of this study is to determine whether patients usually taking Vitamin K&#xD;
      Antagonists (VKAs) exhibit a poorer global cognitive performance than control patients&#xD;
      (matched on age, gender and indication for anticoagulation) taking direct oral anticoagulants&#xD;
      (DOACs).&#xD;
&#xD;
      The secondary objectives are:&#xD;
&#xD;
        -  to determine whether patients usually taking VKAs are more likely to have moderate to&#xD;
           severe cognitive disorders than matched controls taking DOACs.&#xD;
&#xD;
        -  to determine whether VKAs intake is associated with poorer executive functions.&#xD;
&#xD;
        -  to determine on CT scans whether the VKAs intake is associated with a greater volume of&#xD;
           vascular calcifications in the brain compared to the use of DOACs.&#xD;
    </textblock>
  </brief_summary>
  <detailed_description>
    <textblock>
      VKAs are the most common drugs in the treatment and prophylaxis of thromboembolic events in&#xD;
      older adults. Their action is mediated by decrease in the bioavailability of the active form&#xD;
      of vitamin K. However, vitamin K participates in brain health and function by regulating the&#xD;
      synthesis of sphingolipids, a constituent of the myelin sheath and the neurons membrane, and&#xD;
      through the biological activation of vitamin K-dependent proteins (VKDPs) involved in neuron&#xD;
      survival. Epidemiological studies have reported a positive association between higher serum&#xD;
      vitamin K concentration and better verbal episodic memory performance in older adults, and an&#xD;
      inverse association between dietary vitamin K intakes and cognitive complaint/cognitive&#xD;
      disorders/behavioral disorders. VKAs, which deplete the active form of vitamin K, may thus be&#xD;
      responsible for neurological disorders. CNS abnormalities were observed in newborns exposed&#xD;
      in utero to VKA. Similarly, in two cross-sectional studies, the use of VKAs was directly&#xD;
      associated with cognitive disorders in older adults, and with a lower volume of gray matter&#xD;
      in the hippocampus.&#xD;
&#xD;
      However, the main limitation of these previous studies was that the different associations&#xD;
      reported may actually be explained by the thromboembolic pathology justifying the use of VKA&#xD;
      such as atrial fibrillation with potential adverse consequences on the brain.&#xD;
&#xD;
      Thus, the use of DOACs could serve as an ideal comparator, as their indications are similar&#xD;
      to those of VKAs but which mechanism does not interfere with vitamin K.&#xD;
&#xD;
      The investigators hypothesize that 1) geriatric patients usually taking VKAs may have lower&#xD;
      cognitive performance than those usually taking DOACs; 2) there is an association between VKA&#xD;
      intake and cognitive performance in geriatric patients, including after adjustment on the&#xD;
      indication for anticoagulation; and 3) that geriatric patients usually taking VKAs exhibit&#xD;
      brain changes compared to those usually taking DOACs, including greater calcification burden.&#xD;
    </textblock>
  </detailed_description>
  <overall_status>Unknown status</overall_status>
  <last_known_status>Not yet recruiting</last_known_status>
  <start_date type="Anticipated">September 2017</start_date>
  <completion_date type="Anticipated">September 2018</completion_date>
  <primary_completion_date type="Anticipated">September 2018</primary_completion_date>
  <study_type>Observational</study_type>
  <has_expanded_access>No</has_expanded_access>
  <study_design_info>
    <observational_model>Case-Control</observational_model>
    <time_perspective>Retrospective</time_perspective>
  </study_design_info>
  <primary_outcome>
    <measure>Comparison of the global cognitive performance between geriatric patients exposed and non-exposed to VKA</measure>
    <time_frame>Baseline</time_frame>
    <description>Global cognitive performance is assessed by the Mini-Mental State Examination (MMSE) score</description>
  </primary_outcome>
  <secondary_outcome>
    <measure>Comparison of moderate-to-severe dementia diagnosis between geriatric patients exposed and non-exposed to VKA</measure>
    <time_frame>Baseline</time_frame>
    <description>Moderate-to-severe dementia defined as a MMSE score &lt; 20 / 30</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Comparison of the executive functions between geriatric patients exposed and non-exposed to VKA</measure>
    <time_frame>Baseline</time_frame>
    <description>Executive functioning is assessed by the Frontal Assessment Battery (FAB) score</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Evaluation of the volume of vascular calcifications in the brain according to the use of VKAs</measure>
    <time_frame>Baseline</time_frame>
    <description>Semi-automated measure of the volume of vascular calcifications in the brain based on CT scan</description>
  </secondary_outcome>
  <number_of_groups>2</number_of_groups>
  <enrollment type="Anticipated">100</enrollment>
  <condition>Neurocognitive Disorders</condition>
  <arm_group>
    <arm_group_label>Exposed to VKA</arm_group_label>
    <description>VKA intake Patients who have been taking VKA for at least 3 months</description>
  </arm_group>
  <arm_group>
    <arm_group_label>Non-exposed to VKA</arm_group_label>
    <description>DOAC intake Patients who have been taking DOAC for at least 3 months</description>
  </arm_group>
  <eligibility>
    <study_pop>
      <textblock>
        Patients are recruited in the memory clinic and geriatric day hospital of the University&#xD;
        Hospital of Angers, France&#xD;
      </textblock>
    </study_pop>
    <sampling_method>Non-Probability Sample</sampling_method>
    <criteria>
      <textblock>
        Inclusion Criteria:&#xD;
&#xD;
          -  Age 70 years and over&#xD;
&#xD;
          -  To be seen in consultation or day hospital in the department of geriatrics from&#xD;
             01/01/2015 to 31/12/2016&#xD;
&#xD;
          -  Exposed :&#xD;
&#xD;
               -  Patients who have been taking VKA for at least 3 months for atrial fibrillation&#xD;
                  or pulmonary embolism, with INR between 2 and 3&#xD;
&#xD;
          -  Non-exposed:&#xD;
&#xD;
               -  Patients who have been taking DOAC for at least 3 months for atrial fibrillation&#xD;
                  or pulmonary embolism&#xD;
&#xD;
               -  Matched on age (± 5 years), gender and indication for anticoagulation&#xD;
&#xD;
        Exclusion Criteria:&#xD;
&#xD;
          -  Severe kidney failure (creatinine clearance &lt; 30 mL/min)&#xD;
&#xD;
          -  Language other than French&#xD;
      </textblock>
    </criteria>
    <gender>All</gender>
    <minimum_age>70 Years</minimum_age>
    <maximum_age>N/A</maximum_age>
    <healthy_volunteers>No</healthy_volunteers>
  </eligibility>
  <overall_contact>
    <last_name>Cedric ANNWEILER, MD, PhD</last_name>
    <phone>++33 2 41 35 54 86</phone>
    <email>cedric.annweiler@chu-angers.fr</email>
  </overall_contact>
  <location>
    <facility>
      <name>Angers University Hospital</name>
      <address>
        <city>Angers</city>
        <zip>49933</zip>
        <country>France</country>
      </address>
    </facility>
    <contact>
      <last_name>Cedric ANNWEILER, MD, PhD</last_name>
      <phone>++33 2 41 35 54 86</phone>
      <email>cedric.annweiler@chu-angers.fr</email>
    </contact>
    <investigator>
      <last_name>Antoine BRANGIER, MD, BS</last_name>
      <role>Principal Investigator</role>
    </investigator>
  </location>
  <location_countries>
    <country>France</country>
  </location_countries>
  <verification_date>August 2017</verification_date>
  <study_first_submitted>September 4, 2017</study_first_submitted>
  <study_first_submitted_qc>September 7, 2017</study_first_submitted_qc>
  <study_first_posted type="Actual">September 8, 2017</study_first_posted>
  <last_update_submitted>September 12, 2017</last_update_submitted>
  <last_update_submitted_qc>September 12, 2017</last_update_submitted_qc>
  <last_update_posted type="Actual">September 13, 2017</last_update_posted>
  <responsible_party>
    <responsible_party_type>Sponsor</responsible_party_type>
  </responsible_party>
  <condition_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Neurocognitive Disorders</mesh_term>
  </condition_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/NCT03276377
org study id: 2017/19
nct id: NCT03276377
lead sponsor: 
has dmc: No
is fda regulated drug: No
is fda regulated device: No
The primary objective of this study is to determine whether patients usually taking Vitamin K
      Antagonists (VKAs) exhibit a poorer global cognitive performance than control patients
      (matched on age, gender and indication for anticoagulation) taking direct oral anticoagulants
      (DOACs).

      The secondary objectives are:

        -  to determine whether patients usually taking VKAs are more likely to have moderate to
           severe cognitive disorders than matched controls taking DOACs.

        -  to determine whether VKAs intake is associated with poorer executive functions.

        -  to determine on CT scans whether the VKAs intake is associated with a greater volume of
           vascular calcifications in the brain compared to the use of DOACs.
VKAs are the most common drugs in the treatment and prophylaxis of thromboembolic events in
      older adults. Their action is mediated by decrease in the bioavailability of the active form
      of vitamin K. However, vitamin K participates in brain health and function by regulating the
      synthesis of sphingolipids, a constituent of the myelin sheath and the neurons membrane, and
      through the biological activation of vitamin K-dependent proteins (VKDPs) involved in neuron
      survival. Epidemiological studies have reported a positive association between higher serum
      vitamin K concentration and better verbal episodic memory performance in older adults, and an
      inverse association between dietary vitamin K intakes and cognitive complaint/cognitive
      disorders/behavioral disorders. VKAs, which deplete the active form of vitamin K, may thus be
      responsible for neurological disorders. CNS abnormalities were observed in newborns exposed
      in utero to VKA. Similarly, in two cross-sectional studies, the use of VKAs was directly
      associated with cognitive disorders in older adults, and with a lower volume of gray matter
      in the hippocampus.

      However, the main limitation of these previous studies was that the different associations
      reported may actually be explained by the thromboembolic pathology justifying the use of VKA
      such as atrial fibrillation with potential adverse consequences on the brain.

      Thus, the use of DOACs could serve as an ideal comparator, as their indications are similar
      to those of VKAs but which mechanism does not interfere with vitamin K.

      The investigators hypothesize that 1) geriatric patients usually taking VKAs may have lower
      cognitive performance than those usually taking DOACs; 2) there is an association between VKA
      intake and cognitive performance in geriatric patients, including after adjustment on the
      indication for anticoagulation; and 3) that geriatric patients usually taking VKAs exhibit
      brain changes compared to those usually taking DOACs, including greater calcification burden.
observational model: Case-Control
time perspective: Retrospective
measure: Comparison of the global cognitive performance between geriatric patients exposed and non-exposed to VKA
time frame: Baseline
description: Global cognitive performance is assessed by the Mini-Mental State Examination (MMSE) score
measure: Comparison of moderate-to-severe dementia diagnosis between geriatric patients exposed and non-exposed to VKA
time frame: Baseline
description: Moderate-to-severe dementia defined as a MMSE score < 20 / 30
measure: Comparison of the executive functions between geriatric patients exposed and non-exposed to VKA
time frame: Baseline
description: Executive functioning is assessed by the Frontal Assessment Battery (FAB) score
measure: Evaluation of the volume of vascular calcifications in the brain according to the use of VKAs
time frame: Baseline
description: Semi-automated measure of the volume of vascular calcifications in the brain based on CT scan
arm group label: Exposed to VKA
description: VKA intake Patients who have been taking VKA for at least 3 months
arm group label: Non-exposed to VKA
description: DOAC intake Patients who have been taking DOAC for at least 3 months
study pop: 
sampling method: Non-Probability Sample
criteria: 
gender: All
minimum age: 70 Years
maximum age: N/A
healthy volunteers: No
last name: Cedric ANNWEILER, MD, PhD
phone: ++33 2 41 35 54 86
email: cedric.annweiler@chu-angers.fr
facility: 
contact: 
investigator: 
country: France
responsible party type: Sponsor
mesh term: Neurocognitive Disorders